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Ansari M, Rhee TG, Santucci MC, Nikayin S. Does BMI matter when treating depression with esketamine? A retrospective analysis of real-world data. J Affect Disord 2025; 381:22-28. [PMID: 40185405 DOI: 10.1016/j.jad.2025.03.198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 03/15/2025] [Accepted: 03/31/2025] [Indexed: 04/07/2025]
Abstract
OBJECTIVE Intranasal (IN) esketamine was approved as a therapy for treatment-resistant depression in March 2019. There continues to be interest in the field to better understand factors associated with response to treatment. The aim of the current study is to assess the association between BMI and response to esketamine. METHODS A retrospective analysis was conducted on all patients treated with intranasal esketamine at the Yale Interventional Psychiatry Service between January 2015 and May 2023. The primary outcome was the association between BMI (ctegorized as obese vs. non-obese) and response to treatment (≥50 % improvement) by Montgomery-Åsberg Depression Rating Scale (MADRS). Statistical models, including generalized linear mixed-effects models were employed. RESULTS A total of 190 patients met criteria for inclusion in the study, out of which 34.2 % were categorized as obese. Patients with obesity were significantly more likely to respond to esketamine treatment (RR = 1.63; p = 0.033) compared to non-obese patients. No linear association between BMI and treatment response was observed when BMI was treated as a continuous variable (RR = 1.02, p = 0.163). CONCLUSION Obesity appears to be associated with a higher response rate to intranasal esketamine treatment for depression. Although the underlying mechanisms of this association are still unknown, increased body fat may prolong the presence of lipid-soluble compounds such as ketamine/esketamine or their active metabolites.
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Affiliation(s)
- Mina Ansari
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Yale Depression Research Program (YDRP), Yale University, New Haven, CT 06511, USA
| | - Taeho Greg Rhee
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Mia C Santucci
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Yale Depression Research Program (YDRP), Yale University, New Haven, CT 06511, USA
| | - Sina Nikayin
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Yale Depression Research Program (YDRP), Yale University, New Haven, CT 06511, USA; Interventional Psychiatry Services, Yale Psychiatry Hospital, New Haven, CT 06519, USA.
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Gao X, Chen T, Zhou F, Sun Y, Zhang J, Li X, Zhao W, Li Y, Shi Y, Niu K, Wang Y, Zhang Y, Zhang W. The association between different insulin resistance surrogates and all-cause mortality and cardiovascular mortality in patients with metabolic dysfunction-associated steatotic liver disease. Cardiovasc Diabetol 2025; 24:200. [PMID: 40346671 PMCID: PMC12065324 DOI: 10.1186/s12933-025-02758-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/26/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with insulin resistance (IR). However, the prognostic value of different alternative IR surrogates in patients with MASLD remains unclear. This study aimed to evaluate the association between various IR indices and all-cause mortality and cardiovascular mortality in MASLD patients. METHODS A total of 8,753 adults aged ≥ 20 years with MASLD from the National Health and Nutrition Examination Survey (NHANES, 2003-2018) were included, and their mortality data were obtained from the National Death Index (NDI). Insulin resistance surrogates [including the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference index, TyG-waist-to-height ratio index, and Homeostatic Model Assessment for IR] were stratified into quartiles. Cox proportional hazards models, receiver operating characteristic (ROC) curve analysis, restricted cubic spline (RCS), mediation analyses, and subgroup analyses were used to explore the associations between these indices and all-cause mortality as well as cardiovascular mortality in MASLD patients. RESULTS During a median follow-up of 98 months, 1,234 deaths were observed, including 409 cardiovascular disease (CVD)-related deaths. In the fully adjusted model, higher quartiles of TyG-related indices were significantly associated with an increased risk of all-cause mortality in MASLD patients. Furthermore, the TyG-BMI index was associated with both all-cause mortality and CVD mortality [all-cause mortality: HR (95% CI) 2.84 (1.73-4.67), P < 0.001; CVD mortality: HR (95% CI) 5.32 (2.26-12.49), P < 0.001]. The RCS analyses indicated a U-shaped relationship between TyG-BMI and mortality, with a threshold value of 270.49. Subgroup analyses demonstrated that TyG-related indices had stronger associations with mortality in elderly MASLD patients. CONCLUSIONS Our findings highlight the prognostic value of IR indices, particularly TyG-BMI index, in predicting all-cause mortality and CVD mortality in MASLD patients.
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Affiliation(s)
- Xin Gao
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Tianyi Chen
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Feilong Zhou
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Yanmei Sun
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Jiaqi Zhang
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Xinhao Li
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Weijie Zhao
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Yunxin Li
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Yanlong Shi
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Kaiyi Niu
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Yizhu Wang
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China
| | - Yewei Zhang
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan 121, Nanjing, Jiangsu Province, China.
- Department of Hepatobiliary Surgery, The Second Hospital of Shangdong University, Jinan, Shandong Province, China.
| | - Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
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Patel AH, Koysombat K, Pierret A, Young M, Comninos AN, Dhillo WS, Abbara A. Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential. Ann N Y Acad Sci 2024; 1540:21-46. [PMID: 39287750 DOI: 10.1111/nyas.15220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin-releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss-often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA.
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Affiliation(s)
- Aaran H Patel
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
- Department of Endocrinology, Chelsea and Westminster Hospital, London, UK
| | - Kanyada Koysombat
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Aureliane Pierret
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
| | - Megan Young
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
| | - Alexander N Comninos
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Waljit S Dhillo
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Ali Abbara
- Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
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Carrera-Bastos P, Fontes-Villalba M, Ahrén B, Lindblad U, Råstam L, Frostegård J, Åkerfeldt T, Granfeldt Y, Sundquist K, Jönsson T. Total adiponectin in indigenous Melanesians on Kitava. Am J Hum Biol 2024; 36:e24134. [PMID: 38989782 DOI: 10.1002/ajhb.24134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 07/01/2024] [Accepted: 07/02/2024] [Indexed: 07/12/2024] Open
Abstract
OBJECTIVES Experimental and small human studies have indicated that high total adiponectin levels have beneficial cardiometabolic effects. In contrast, however, high total adiponectin levels are also associated with higher all-cause and cardiovascular mortality in thoroughly adjusted epidemiological studies. To gain further insight into these seemingly contradictory results, we report results on total adiponectin from the indigenous Melanesian population of Kitava, Trobriand Islands, Papua New Guinea, where an apparent absence of cardiometabolic disease has been previously reported. METHODS Fasting levels of serum total adiponectin were measured cross-sectionally in ≥40-year-old Kitavans (n = 102) and Swedish controls matched for age and sex (n = 108). Multivariable linear regression was used for the analysis of associations with total adiponectin when controlled for group, sex, smoking, hypertension and/or type 2 diabetes, age, and body mass index. RESULTS Total adiponectin was lower for Kitavans compared to Swedish controls (Median [Mdn] 4.6 μg/mL, range 1.0-206 μg/mL and Mdn 9.7 μg/mL, range 3.1-104 μg/mL, respectively, r = .64, p < .001). Lower total adiponectin was associated with Kitavan group, male sex (only in Swedish controls), smoking (only in Kitavans and Swedish controls combined), younger age (not in Swedish controls), higher BMI, lower total, low-density lipoprotein, high-density lipoprotein (HDL) (only in Kitavans and Swedish controls combined), and non-HDL cholesterol, and higher anti-PC IgG (only in Kitavans and Swedish controls combined). CONCLUSION Total adiponectin in Kitavans was significantly lower than in Swedish controls.
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Affiliation(s)
- Pedro Carrera-Bastos
- Center for Primary Health Care Research, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
| | - Maelán Fontes-Villalba
- Center for Primary Health Care Research, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
| | - Bo Ahrén
- Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
| | - Ulf Lindblad
- School of Public Health and Community Medicine, University of Gothenburg, Göteborg, Sweden
| | - Lennart Råstam
- Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
| | - Johan Frostegård
- IMM, Karolinska Institute, Unit of Immunology and chronic disease, Stockholm, Sweden
| | - Torbjörn Åkerfeldt
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- Uppsala University Hospital, Uppsala, Sweden
| | - Yvonne Granfeldt
- Department of Food Technology, Engineering and Nutrition, Lund, Lund University, Sweden
| | - Kristina Sundquist
- Center for Primary Health Care Research, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
- University Clinic Primary Care Skåne, Region Skåne, Sweden
| | - Tommy Jönsson
- Center for Primary Health Care Research, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden
- University Clinic Primary Care Skåne, Region Skåne, Sweden
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Myasoedova VA, Bertolini F, Valerio V, Moschetta D, Massaiu I, Rusconi V, De Giorgi D, Ciccarelli M, Parisi V, Poggio P. The Role of Adiponectin and Leptin in Fibro-Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis. Biomedicines 2024; 12:1977. [PMID: 39335491 PMCID: PMC11428218 DOI: 10.3390/biomedicines12091977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). METHODS A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger's test and funnel plots. RESULTS Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = -0.143, 95% CI: -0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: -0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). CONCLUSION This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.
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Affiliation(s)
| | | | | | | | | | | | | | - Michele Ciccarelli
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy
| | - Valentina Parisi
- Department of Translational Medical Sciences, Federico II University, 80138 Naples, Italy
| | - Paolo Poggio
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
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Habib SS, Al-khlaiwi T, Al-khliwi H, Habib SM, Habib SA, Habib SH, Khan A. Adiponectin and TNFα in relation to glucometabolic control in patients with type 2 diabetes mellitus. J Family Med Prim Care 2024; 13:2741-2745. [PMID: 39070992 PMCID: PMC11272019 DOI: 10.4103/jfmpc.jfmpc_1896_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/13/2024] [Accepted: 02/23/2024] [Indexed: 07/30/2024] Open
Abstract
Background The correlation of adiponectin and serum tumor necrosis factor alpha (TNFα) with glucometabolic parameters in diabetes mellitus (DM) needs further studies. We aimed in this study to evaluate the relationship between adiponectin and TNFα with glucometabolic parameters in patients with type 2 DM (T2DM). Methods We conducted a cross-sectional study in the Department of Physiology, College of Medicine, King Saud University, Saudi Arabia. The sample size was 117 from the diabetes clinic of King Abdul-Aziz University hospital through the convenience sampling technique. Subjects were grouped into control (healthy) subjects (53) with no chronic diseases and the diabetic group (64) with confirmed T2DM. Socio-demographic data were collected along with the serum blood sample to analyze the variables. Results Adiponectin was significantly high in healthy subjects compared to the diabetic group (control: 14.4 ± 4.3, T2DM: 11.0 ± 4.1, P = 0.000), while TNFα was higher in the T2DM group (7.8 ± 2.7) than in the control group (6.6 ± 2.9, P = 0.024). TNFα was negatively correlated with adiponectin in the control group (-0.279) and in diabetic subjects (-0.311) and positively correlated with HbA1c in the diabetic group (0.319) and triglycerides (0.252). Adiponectin was positively correlated with HDL in the control group (0.252) and in diabetic subjects (0.326). There was an inverse correlation between TNFα and adiponectin. Conclusion Adiponectin is higher in healthy subjects than in diabetic patients, while TNFα is higher in diabetic patients. In addition, adiponectin is positively correlated with HDL in healthy as well as diabetic patients. TNFα is positively correlated with HbA1c and triglycerides.
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Affiliation(s)
- Syed Shahid Habib
- Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Thamir Al-khlaiwi
- Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Huthayfah Al-khliwi
- Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Syed Mohammad Habib
- College of Medicine, Sulaiman Al Rajhi University, Al Bukayriah, Saudi Arabia
| | - Syed Abubakar Habib
- College of Medicine, Sulaiman Al Rajhi University, Al Bukayriah, Saudi Arabia
| | - Syed Hamid Habib
- Department of Basic Sciences, Khyber Medical University, Peshawar, Pakistan
| | - Adeena Khan
- Department of Radiology, King Saud University, Riyadh, Saudi Arabia
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Fawaz S, Martin Alonso A, Qiu Y, Ramnath R, Stowell-Connolly H, Gamez M, May C, Down C, Coward RJ, Butler MJ, Welsh GI, Satchell SC, Foster RR. Adiponectin Reduces Glomerular Endothelial Glycocalyx Disruption and Restores Glomerular Barrier Function in a Mouse Model of Type 2 Diabetes. Diabetes 2024; 73:964-976. [PMID: 38530908 DOI: 10.2337/db23-0455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 02/26/2024] [Indexed: 03/28/2024]
Abstract
Adiponectin has vascular anti-inflammatory and protective effects. Although adiponectin protects against the development of albuminuria, historically, the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnCs). In diabetes, eGlx dysfunction occurs before podocyte damage; hence, we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD). Globular adiponectin (gAd) activated AMPK signaling in human GEnCs through AdipoR1. It significantly reduced eGlx shedding and the tumor necrosis factor-α (TNF-α)-mediated increase in syndecan-4 (SDC4) and MMP2 mRNA expression in GEnCs in vitro. It protected against increased TNF-α mRNA expression in glomeruli isolated from db/db mice and against expression of genes associated with glycocalyx shedding (namely, SDC4, MMP2, and MMP9). In addition, gAd protected against increased glomerular albumin permeability (Ps'alb) in glomeruli isolated from db/db mice when administered intraperitoneally and when applied directly to glomeruli (ex vivo). Ps'alb was inversely correlated with eGlx depth in vivo. In summary, adiponectin restored eGlx depth, which was correlated with improved glomerular barrier function, in diabetes. ARTICLE HIGHLIGHTS
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Affiliation(s)
- Sarah Fawaz
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Aldara Martin Alonso
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Yan Qiu
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Raina Ramnath
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Holly Stowell-Connolly
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Monica Gamez
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Carl May
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Colin Down
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Richard J Coward
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Matthew J Butler
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Gavin I Welsh
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Simon C Satchell
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
| | - Rebecca R Foster
- Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K
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Idrizaj E, Nistri S, Nardini P, Baccari MC. Adiponectin affects ileal contractility of mouse preparations. Am J Physiol Gastrointest Liver Physiol 2024; 326:G187-G194. [PMID: 38111974 DOI: 10.1152/ajpgi.00203.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/20/2023]
Abstract
Adiponectin (ADPN) has been reported to induce inhibitory effects on gastric motor activity, which, being a source of peripheral satiety signals, would contribute to the central anorexigenic effects of the hormone in rodents. However, peripheral satiety signals can also originate from the small intestine. Since there are no data on the effects of ADPN in this gut region, the present study aimed to investigate whether ADPN affects murine ileal contractility. Immunofluorescence experiments and Western blot were also performed to reveal the expression of ADPN receptors. Mechanical responses of ileal preparations were recorded in vitro via force-displacement transducers. Preparations showed a tetrodotoxin- and atropine-insensitive spontaneous contractile activity. Electrical field stimulation (EFS) induced tetrodotoxin- and atropine-sensitive contractile responses. ADPN induced a decay of the basal tension and decreased the amplitude of either the spontaneous contractility or the EFS-induced excitatory responses. All ADPN effects were abolished by the nitric oxide (NO) synthesis inhibitor NG-nitro l-arginine. The expression of the ADPN receptor, AdipoR1, but not AdipoR2, was also revealed in enteric glial cells. The present results offer the first evidence that ADPN acts on ileal preparations. The hormone exerts inhibitory effects, likely involving AdipoR1 on enteric glial cells and NO. From a physiological point of view, it could be hypothesized that the depressant action of ADPN on ileal contractility represents an additional peripheral satiety signal which, as also described for the ileal brake, could contribute to the central anorexigenic effects of the hormone.NEW & NOTEWORTHY This study provides the first evidence that adiponectin (ADPN) is able to act on ileal preparations. Functional results demonstrate that the hormone, other than causing a slight decay of the basal tension, depresses the amplitude of both spontaneous contractility and neurally induced excitatory responses of the mouse ileum through the involvement of nitric oxide. The expression of the ADPN receptor AdipoR1 and its localization on glial cells was revealed by Western blot and immunofluorescence analysis.
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Affiliation(s)
- Eglantina Idrizaj
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Firenze, Italy
| | - Silvia Nistri
- Department of Experimental and Clinical Medicine, Imaging Platform, University of Florence, Firenze, Italy
| | - Patrizia Nardini
- Department of Experimental and Clinical Medicine, Imaging Platform, University of Florence, Firenze, Italy
| | - Maria Caterina Baccari
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Firenze, Italy
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Tan L, Yan W, Yang W, Kamionka A, Lipowski M, Zhao Z, Zhao G. Effect of exercise on inflammatory markers in postmenopausal women with overweight and obesity: A systematic review and meta-analysis. Exp Gerontol 2023; 183:112310. [PMID: 37844768 DOI: 10.1016/j.exger.2023.112310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 10/10/2023] [Accepted: 10/13/2023] [Indexed: 10/18/2023]
Abstract
IMPORTANCE Postmenopausal women affected by overweight and obesity are susceptible to a variety of diseases due to inflammation. Exercise may reduce the risk of disease by attenuating low-grade chronic inflammation. OBJECTIVE We conducted a systematic review and meta-analysis to investigate the effects of exercise on inflammatory markers in postmenopausal women struggling with overweight and obesity. METHOD Literature as of May 2023 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO and English-language randomized controlled trials (RCTs) that meet the inclusion criteria were selected. Studies were included based on the following criteria: (A) Written in English; (B) RCTs; (C) Postmenopausal women impacted by overweight and obesity as research objects; (D) Outcome measurements include CRP, TNF-α, IL-6, and adiponectin; (E) Duration of the exercise intervention is eight weeks. RESULTS A total of 34 articles and 2229 participants were included. Exercise can significantly reduce the level of C-reactive protein (CRP) (MD: -0.59, 95 % CI: -0.87 to -0.31, p < 0.00001), tumor necrosis factor-α (TNF-α) (MD: -0.65, 95 % CI: -0.94 to -0.35, p < 0.00001), interleukin-6 (IL-6) (MD: -0.48, 95 % CI: -0.75 to -0.21, p < 0.00001), and exercise can significantly increase the level of adiponectin (MD: 0.33, 95 % CI: 0.02 to 0.65, p = 0.04) in women impacted by overweight and obesity. CONCLUSION These results suggest that exercise may be an effective intervention for reducing pro-inflammatory markers and increasing adiponectin in postmenopausal women impacted by overweight and obesity. The findings may provide clinicians and healthcare professionals with insights into the implementation of exercise programs for postmenopausal women living with overweight and obesity.
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Affiliation(s)
- Liang Tan
- Faculty of Physical Culture, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland; Changsha Commerce & Tourism College, 410116, Changsha, China.
| | - Weihua Yan
- School of Management, Beijing Sport University, 100084, Beijing, China.
| | - Weilin Yang
- Faculty of Physical Culture, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland.
| | - Agata Kamionka
- Faculty of Physical Culture, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland.
| | - Mariusz Lipowski
- Faculty of Social and Humanities, University WSB Merito, 80-266 Gdansk, Poland.
| | - Zijian Zhao
- Physical Education Institute (Main Campus), Zhengzhou University, 450001, Zhengzhou, China.
| | - Gang Zhao
- Changsha Commerce & Tourism College, 410116, Changsha, China.
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10
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Peng J, Chen Q, Wu C. The role of adiponectin in cardiovascular disease. Cardiovasc Pathol 2023; 64:107514. [PMID: 36634790 DOI: 10.1016/j.carpath.2022.107514] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 01/11/2023] Open
Abstract
Cardiovascular disease (CVD) is a common disease that seriously threatens the health of human beings, especially middle-aged and elderly people over 50 years old. It has the characteristics of high prevalence, high disability rate and high mortality rate. Previous studies have shown that adiponectin has therapeutic effects on a variety of CVDs. As a key adipokine, adiponectin, is an abundant peptide-regulated hormone that is mainly released by adipocytes and cardiomyocytes, as well as endothelial and skeletal cells. Adiponectin can protect against CVD by improving lipid metabolism, protecting vascular endothelial cells and inhibiting foam cell formation and vascular smooth muscle cell proliferation. Further investigation of the molecular and cellular mechanisms underlying the adiponectin system may provide new ideas for the treatment of CVD. Herein, this review aims to describe the structure and function of adiponectin and adiponectin receptors, introduce the function of adiponectin in the protection of cardiovascular disease and analyze the potential use and clinical significance of this hormone in the protection and treatment of cardiovascular disease, which shows that adiponectin can be expected to become a new therapeutic target and biomarker for the diagnosis and treatment of CVD.
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Affiliation(s)
- Jin Peng
- Clinical Medical Research Center, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Qian Chen
- Clinical Medical Research Center, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Chuncao Wu
- Insititution of Chinese Materia Medica Preparation, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
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11
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Scott SR, Millwood SN, Manczak EM. Adipocytokine correlates of childhood and adolescent mental health: A systematic review. Dev Psychobiol 2023; 65:e22379. [PMID: 36946681 DOI: 10.1002/dev.22379] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 11/13/2022] [Accepted: 01/17/2023] [Indexed: 03/14/2023]
Abstract
The objective of this systematic review was to determine the current state of the literature regarding how adipocytokines associate with mental health symptoms/disorders in youth. Findings summarized in this review suggested that in neurodevelopmental disorders, higher levels of leptin, ghrelin, resistin, and visfatin as well as lower levels of adiponectin, retinol-binding protein 4, and progranulin predicted increased risk for or were conflated with autism spectrum disorder. Adipocytokine correlates of attention-deficit hyperactivity disorder and related symptoms included higher apelin, higher leptin-to-adiponectin ratio, and lower adiponectin. Evidence from studies examining anxiety symptoms evinced mixed results regarding leptin, and one study suggested higher levels of ghrelin. Depressive symptoms correlated with higher leptin and ghrelin. Research examining posttraumatic stress symptoms found higher levels of ghrelin. In research examining broadband symptoms, conflicting results emerged for associations between internalizing symptoms (i.e., symptoms of emotional stress) and leptin in youth. Low levels of adiponectin and high levels of leptin predicted externalizing symptoms. Total symptom difficulties were associated with a higher leptin-to-adiponectin ratio. Our findings suggest that adipocytokines may be an important set of biomarkers to consider as underlying mechanisms contributing to developmental psychopathology.
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Affiliation(s)
- Samantha R Scott
- Biology, Environments, and Mood Studies Lab, Department of Psychology, University of Denver, Denver, Colorado, USA
| | - Summer N Millwood
- Biology, Environments, and Mood Studies Lab, Department of Psychology, University of Denver, Denver, Colorado, USA
| | - Erika M Manczak
- Biology, Environments, and Mood Studies Lab, Department of Psychology, University of Denver, Denver, Colorado, USA
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12
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Yang NI, Kuo LT, Lee CC, Ting MK, Wu IW, Chen SW, Hsu KH. Associations of Three-Dimensional Anthropometric Body Surface Scanning Measurements and Coronary Artery Disease. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:570. [PMID: 36984571 PMCID: PMC10056801 DOI: 10.3390/medicina59030570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 03/01/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023]
Abstract
Background and Objectives: The relationship between three-dimensional (3D) scanning-derived body surface measurements and biomarkers in patients with coronary artery disease (CAD) were assessed. Methods and Methods: The recruitment of 98 patients with CAD confirmed by cardiac catheterization and 98 non-CAD patients were performed between March 2016 and December 2017. A health questionnaire on basic information, life style variables, and past medical and family history was completed. 3D body surface measurements and biomarkers were obtained. Differences between the two groups were assessed and multivariable analysis performed. Results: It was found that chest width (odds ratio [OR] 0.761, 95% confidence interval [CI] = 0.586-0.987, p = 0.0399), right arm length (OR 0.743, 95% CI = 0.632-0.875, p = 0.0004), waist circumference (OR 1.119, 95% CI = 1.035-1.21, p = 0.0048), leptin (OR 1.443, 95% CI = 1.184-1.76, p = 0.0003), adiponectin (OR 0.978, 95% CI = 0.963-0.994, p = 0.006), and interleukin 6 (OR 1.181, 95% CI = 1.021-1.366, p = 0.0254) were significantly associated with CAD. The combination of biomarker scores and body measurement scores had the greatest area under the curve and best association with CAD (area under the curve of 0.8049 and 95% CI = 0.7440-0.8657). Conclusions: Our study suggests that 3D derived body surface measurements in combination with leptin, adiponectin, and interleukin 6 levels may direct us to those at risk of CAD, allowing a non-invasive approach to identifying high-risk patients.
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Affiliation(s)
- Ning-I Yang
- Division of Cardiology, Department of Internal Medicine, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Li-Tang Kuo
- Division of Cardiology, Department of Internal Medicine, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Chin-Chan Lee
- Division of Nephrology, Department of Internal Medicine, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Ming-Kuo Ting
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - I-Wen Wu
- Division of Nephrology, Department of Internal Medicine, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Shuo-Wei Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Kuang-Hung Hsu
- Laboratory for Epidemiology, Department of Health Care Management, Chang Gung University, Taoyuan 333, Taiwan
- Department of Health Care Management, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of Safety, Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 243, Taiwan
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13
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Marstein HS, Witczak BN, Godang K, Olarescu NC, Schwartz T, Flatø B, Molberg Ø, Bollerslev J, Sjaastad I, Sanner H. Adipokine profile in long-term juvenile dermatomyositis, and associations with adipose tissue distribution and cardiac function: a cross-sectional study. RMD Open 2023; 9:rmdopen-2022-002815. [PMID: 36828644 PMCID: PMC9972436 DOI: 10.1136/rmdopen-2022-002815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 02/02/2023] [Indexed: 02/26/2023] Open
Abstract
OBJECTIVES In long-term juvenile dermatomyositis (JDM), altered adipose tissue distribution and subclinical cardiac dysfunction have been described. Our aims were to compare adipokine levels in patients with JDM after long-term disease with controls, and explore associations between adipokines and (1) adipose tissue distribution and (2) cardiac function. METHODS The study cohort included 59 patients with JDM (60% female, mean age 25.2 years, mean disease duration 16.9 years), and 59 age/sex-matched controls. Updated Pediatric Rheumatology International Trials Organization criteria for clinically inactive JDM were used to stratify patients into active (JDM-active) or inactive (JDM-inactive) disease groups. Lipodystrophy was clinically assessed in all patients. In all study participants, we measured adipose tissue distribution by dual-energy X-ray absorptiometry and cardiac function by echocardiography. Serum adipokines (adiponectin, apelin-12, lipocalin-2, leptin, visfatin and resistin) were analysed using ELISA. RESULTS Patients with JDM had higher leptin levels compared with controls (p≤0.01). In JDM-active, apelin-12 and visfatin were higher compared with JDM-inactive (p≤0.05). In JDM-total and JDM-active, lower adiponectin correlated with lipodystrophy and total fat mass. Also, systolic dysfunction correlated with: lower adiponectin in JDM-total, JDM-inactive and JDM-active, and with lower apelin-12 in JDM-total and JDM-active and resistin in JDM-active (all p≤0.05). Lower adiponectin correlated with diastolic dysfunction in JDM-total and JDM-active. CONCLUSION After long-term disease, leptin levels were unfavourably regulated in patients with JDM compared with controls, and apelin-12 and visfatin in JDM-active versus JDM-inactive. We found associations between adipokines and both adipose tissue distribution and cardiac systolic function in all patients with JDM, which was most prominent in patients with active disease.
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Affiliation(s)
- Henriette Schermacher Marstein
- Institute of Experimental Medical Research, Oslo University Hospital Ullevaal, Oslo, Norway .,Department of Health Sciences, Oslo New University College, Oslo, Norway.,KG Jebsen Center for Cardiac Research, Oslo University Hospital, Oslo, Norway
| | - Birgit Nomeland Witczak
- Institute of Experimental Medical Research, Oslo University Hospital Ullevaal, Oslo, Norway,KG Jebsen Center for Cardiac Research, Oslo University Hospital, Oslo, Norway
| | - Kristin Godang
- Section of Specialized Endocrinology, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Medical Clinic, Oslo University Hospital, Oslo, Norway
| | - Nicoleta Christina Olarescu
- Section of Specialized Endocrinology, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Medical Clinic, Oslo University Hospital, Oslo, Norway,Institute for Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
| | - Thomas Schwartz
- Institute of Experimental Medical Research, Oslo University Hospital Ullevaal, Oslo, Norway,KG Jebsen Center for Cardiac Research, Oslo University Hospital, Oslo, Norway
| | - Berit Flatø
- Institute for Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway,Department of Rheumatology, Oslo University Hospital, Oslo, Norway
| | - Øyvind Molberg
- Department of Rheumatology, Oslo University Hospital, Oslo, Norway,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Jens Bollerslev
- Section of Specialized Endocrinology, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Medical Clinic, Oslo University Hospital, Oslo, Norway,Institute for Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
| | - Ivar Sjaastad
- Institute of Experimental Medical Research, Oslo University Hospital Ullevaal, Oslo, Norway,KG Jebsen Center for Cardiac Research, Oslo University Hospital, Oslo, Norway,Department of Cardiology, Oslo University Hospital, Oslo, Norway
| | - Helga Sanner
- Department of Health Sciences, Oslo New University College, Oslo, Norway,Department of Rheumatology, Oslo University Hospital, Oslo, Norway
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14
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Guan Y, Zuo F, Zhao J, Nian X, Shi L, Xu Y, Huang J, Kazumi T, Wu B. Relationships of adiponectin to regional adiposity, insulin sensitivity, serum lipids, and inflammatory markers in sedentary and endurance-trained Japanese young women. Front Endocrinol (Lausanne) 2023; 14:1097034. [PMID: 36761190 PMCID: PMC9902352 DOI: 10.3389/fendo.2023.1097034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 01/09/2023] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION This study aims to compare the differences in circulating adiponectin levels and their relationships to regional adiposity, insulin resistance, serum lipid, and inflammatory factors in young, healthy Japanese women with different physical activity statuses. METHODS Adipokines (adiponectin and leptin), full serum lipid, and inflammatory factors [white blood cell counts, C-reactive protein, tumor necrosis factor-α, tissue plasminogen activator inhibitor-1 (PAI-1)] were measured in 101 sedentary and 100 endurance-trained healthy Japanese women (aged 18-23 years). Insulin sensitivity was obtained through a quantitative insulin-sensitivity check index (QUICKI). Regional adiposity [trunk fat mass (TFM), lower-body fat mass (LFM), and arm fat mass (AFM)] was evaluated using the dual-energy X-ray absorptiometry method. RESULTS No significant difference was observed between the sedentary and trained women in terms of adiponectin levels. The LFM-to-TFM ratio and the high-density lipoprotein cholesterol (HDL-C) were the strong positive determinants for adiponectin in both groups. Triglyceride in the sedentary women was closely and negatively associated with adiponectin, as well as PAI-1 in the trained women. The QUICKI level was higher in the trained than sedentary women. However, no significant correlation between adiponectin and insulin sensitivity was detected in both groups. Furthermore, LFM was associated with a favorable lipid profile against cardiovascular diseases (CVDs) in the whole study cohort, but this association became insignificant when adiponectin was taken into account. CONCLUSIONS These findings suggest that adiponectin is primarily associated with regional adiposity and HDL-C regardless of insulin sensitivity and physical activity status in young, healthy women. The associations among adiponectin, lipid, and inflammatory factors are likely different in women with different physical activity statuses. The correlation of LFM and a favorable lipid profile against CVD and adiponectin is likely involved in this association.
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Affiliation(s)
- Yaxin Guan
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
| | - Fan Zuo
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
| | - Juan Zhao
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
| | - Xin Nian
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
| | - Li Shi
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
| | - Yushan Xu
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
| | - Jingshan Huang
- School of Computing, University of South Alabama, Mobile, AL, United States
| | - Tsutomu Kazumi
- Open Research Center for Studying of Lifestyle-Related Diseases, Mukogawa Women’s University, Nishinomiya, Japan
- Department of Food Sciences and Nutrition, School of Human Environmental Science, Mukogawa Women’s University, Nishinomiya, Japan
- Research Institute for Nutrition Sciences, Mukogawa Women’s University, Nishinomiya, Japan
| | - Bin Wu
- Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Medical Center for Endocrine and Metabolic Diseases, Kunming, Yunnan, China
- Open Research Center for Studying of Lifestyle-Related Diseases, Mukogawa Women’s University, Nishinomiya, Japan
- *Correspondence: Bin Wu,
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15
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Yoshida K, Morishima Y, Ano S, Sakurai H, Kuramoto K, Tsunoda Y, Yazaki K, Nakajima M, Sherpa MT, Matsuyama M, Kiwamoto T, Matsuno Y, Ishii Y, Hayashi A, Matsuzaka T, Shimano H, Hizawa N. ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice. J Allergy Clin Immunol 2022; 151:1067-1080.e9. [PMID: 36592705 DOI: 10.1016/j.jaci.2022.12.808] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 11/30/2022] [Accepted: 12/06/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12 to C16 to those with C18, has been recently indicated to affect various immune and inflammatory responses; however, the precise process by which ELOVL6-related lipid dysregulation affects allergic airway inflammation is unclear. OBJECTIVES This study sought to evaluate the biological roles of ELOVL6 in allergic airway responses and investigate whether regulating lipid composition in the airways could be an alternative treatment for asthma. METHODS Expressions of ELOVL6 and other isoforms were examined in the airways of patients who are severely asthmatic and in mouse models of asthma. Wild-type and ELOVL6-deficient (Elovl6-/-) mice were analyzed for ovalbumin-induced, and also for house dust mite-induced, allergic airway inflammation by cell biological and biochemical approaches. RESULTS ELOVL6 expression was downregulated in the bronchial epithelium of patients who are severely asthmatic compared with controls. In asthmatic mice, ELOVL6 deficiency led to enhanced airway inflammation in which lymphocyte egress from lymph nodes was increased, and both type 2 and non-type 2 immune responses were upregulated. Lipidomic profiling revealed that the levels of palmitic acid, ceramides, and sphingosine-1-phosphate were higher in the lungs of ovalbumin-immunized Elovl6-/- mice compared with those of wild-type mice, while the aggravated airway inflammation was ameliorated by treatment with fumonisin B1 or DL-threo-dihydrosphingosine, inhibitors of ceramide synthase and sphingosine kinase, respectively. CONCLUSIONS This study illustrates a crucial role for ELOVL6 in controlling allergic airway inflammation via regulation of fatty acid composition and ceramide-sphingosine-1-phosphate biosynthesis and indicates that ELOVL6 may be a novel therapeutic target for asthma.
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Affiliation(s)
- Kazufumi Yoshida
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Yuko Morishima
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
| | - Satoshi Ano
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Respiratory Medicine, National Hospital Organization Kasumigaura Medical Center, Tsuchiura, Ibaraki, Japan
| | - Hirofumi Sakurai
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kenya Kuramoto
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Yoshiya Tsunoda
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kai Yazaki
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Masayuki Nakajima
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Mingma Thering Sherpa
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Masashi Matsuyama
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Takumi Kiwamoto
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Yosuke Matsuno
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Yukio Ishii
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Akio Hayashi
- Exploratory Research Laboratories, Minase Research Institute, Ono Pharmaceutical Co Ltd, Mishima, Osaka, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Chiyoda, Tokyo, Japan
| | - Takashi Matsuzaka
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Chiyoda, Tokyo, Japan
| | - Hitoshi Shimano
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Chiyoda, Tokyo, Japan
| | - Nobuyuki Hizawa
- Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
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16
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Zahradka P, Taylor CG, Tworek L, Perrault R, M’Seffar S, Murali M, Loader T, Wigle JT. Thrombin-Mediated Formation of Globular Adiponectin Promotes an Increase in Adipose Tissue Mass. Biomolecules 2022; 13:biom13010030. [PMID: 36671414 PMCID: PMC9855379 DOI: 10.3390/biom13010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/15/2022] [Accepted: 11/23/2022] [Indexed: 12/24/2022] Open
Abstract
A decrease in the circulating levels of adiponectin in obesity increases the risk of metabolic complications, but the role of globular adiponectin, a truncated form produced by proteolytic cleavage, has not been defined. The objective of this investigation was to determine how globular adiponectin is generated and to determine whether this process impacts obesity. The cleavage of recombinant full-length adiponectin into globular adiponectin by plasma in vitro was used to identify Gly-93 as the N-terminal residue after proteolytic processing. The amino acid sequence of the cleavage site suggested thrombin was the protease responsible for cleavage, and inhibitors confirmed its likely involvement. The proteolytic site was modified, and this thrombin-resistant mutant protein was infused for 4 weeks into obese adiponectin-knockout mice that had been on a high-fat diet for 8 weeks. The mutation of the cleavage site ensured that globular adiponectin was not generated, and thus did not confound the actions of the full-length adiponectin. Mice infused with the mutant adiponectin accumulated less fat and had smaller adipocytes compared to mice treated with globular adiponectin, and concurrently had elevated fasting glucose. The data demonstrate that generation of globular adiponectin through the action of thrombin increases both adipose tissue mass and adipocyte size, but it has no effect on fasting glucose levels in the context of obesity.
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Affiliation(s)
- Peter Zahradka
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
- Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
- Correspondence: ; Tel.: +1-204-235-3507
| | - Carla G. Taylor
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
- Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Leslee Tworek
- Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Raissa Perrault
- Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Sofia M’Seffar
- Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Megha Murali
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Tara Loader
- Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Jeffrey T. Wigle
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
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17
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Wong SK, Ramli FF, Ali A, Ibrahim N‘I. Genetics of Cholesterol-Related Genes in Metabolic Syndrome: A Review of Current Evidence. Biomedicines 2022; 10:biomedicines10123239. [PMID: 36551995 PMCID: PMC9775320 DOI: 10.3390/biomedicines10123239] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022] Open
Abstract
Metabolic syndrome (MetS) refers to a cluster of metabolic dysregulations, which include insulin resistance, obesity, atherogenic dyslipidemia and hypertension. The complex pathogenesis of MetS encompasses the interplay between environmental and genetic factors. Environmental factors such as excessive nutrients and sedentary lifestyle are modifiable and could be improved by lifestyle modification. However, genetic susceptibility to MetS, a non-modifiable factor, has attracted the attention of researchers, which could act as the basis for future diagnosis, prognosis, and therapy for MetS. Several cholesterol-related genes associated with each characteristic of MetS have been identified, such as apolipoprotein, lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and adiponectin. This review aims to summarize the genetic information of cholesterol-related genes in MetS, which may potentially serve as biomarkers for early prevention and management of MetS.
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Affiliation(s)
- Sok Kuan Wong
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia
| | - Fitri Fareez Ramli
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia
- Clinical Psychopharmacology Research Unit, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK
| | - Adli Ali
- Department of Pediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia
| | - Nurul ‘Izzah Ibrahim
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia
- Correspondence: ; Tel.: +60-39145-9545
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18
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Iioka M, Fukuda S, Maeda N, Natsukawa T, Kita S, Fujishima Y, Sawano H, Nishizawa H, Shimomura I. Time-Series Change of Serum Soluble T-Cadherin Concentrations and Its Association with Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction. J Atheroscler Thromb 2022; 29:1823-1834. [PMID: 35228485 PMCID: PMC9881537 DOI: 10.5551/jat.63305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
AIMS T-cadherin (T-cad) is a specific binding partner of adiponectin (APN), adipocyte-specific secretory protein. APN exhibits organ protection via the T-cad-dependent accumulation onto several tissues such as the aorta, heart, and muscle. Recently, for the first time, we showed that three forms (130, 100, and 30 kDa) of soluble T-cad existed in human serum and correlated with several clinical parameters in patients with type 2 diabetes. Nevertheless, the significance of soluble T-cad has not been elucidated in the acute stage of cardiovascular diseases. We herein examined soluble T-cad concentrations and investigated their clinical significance in patients with emergency hospital admission due to ST-segment elevation myocardial infarction (STEMI). METHODS This observational study enrolled 47 patients with STEMI who were treated via primary percutaneous coronary intervention (PCI). Soluble T-cad and APN concentrations were measured by using an enzyme-linked immunosorbent assay. This study is registered with the University Hospital Medical Information Network (Number: UMIN 000014418). RESULTS Serum concentrations of soluble 130 and 100 kDa T-cad rapidly and significantly decreased after hospitalization and reached the bottom at 72 h after admission (p＜0.001 and p＜0.001, respectively). The patients with high soluble T-cad and low APN concentrations on admission showed a significantly higher area under the curve of serum creatine kinase-MB (p＜0.01). CONCLUSION Serum soluble T-cad concentration changed dramatically in patients with STEMI, and the high T-cad and low APN concentrations on admission were associated with the myocardial infarction size. Further study is needed to investigate the usefulness of categorizing patients with STEMI by serum T-cad and APN for the prediction of severe prognoses.
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Affiliation(s)
- Masahito Iioka
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shiro Fukuda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Norikazu Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan,Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tomoaki Natsukawa
- Department of Emergency and Intensive care, Yodogawa Christian Hospital, Osaka, Japan
| | - Shunbun Kita
- Department of Adipose Management, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yuya Fujishima
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hirotaka Sawano
- Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital, Osaka, Japan
| | - Hitoshi Nishizawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
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19
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Zuo L, Chen X, Liu M, Chen L, Xu W, Chen H, Dong S, Wei Y, Li L, Peng S, Hao G. Road Traffic Noise, Obesity, and the Risk of Incident Type 2 Diabetes: A Cohort Study in UK Biobank. Int J Public Health 2022; 67:1605256. [PMID: 36312318 PMCID: PMC9596764 DOI: 10.3389/ijph.2022.1605256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 09/26/2022] [Indexed: 08/03/2023] Open
Abstract
Objectives: To assess the association of road traffic noise exposure with Type 2 Diabetes (T2D) risk, and to explore the potential moderation effect of obesity. Methods: A total of 305,969 participants from the UK Biobank Cohort - an open access cohort of 500,000 participants recruited in the United Kingdom (UK) between 2006 and 2010 - were included in the study. A Cox proportional hazard model was fitted to assess the association between road traffic noise exposure and T2D. Results: A total of 19,303 participants were diagnosed with T2D during the 11.9-year median follow-up period. For every 10 dB increase in road traffic noise, there was a 4% increase in T2D risk (HR = 1.04, 95%CI: 1.01, 1.07). Besides, a significant positive interaction was observed between obesity and road traffic noise (P interaction <0.001) for the risk of T2D. The association of road traffic noise with T2D was stronger in overweight and obese participants (HR = 1.04, 95% CI: 1.01-1.08), but not significant among lean ones (HR = 0.96, 95% CI: 0.86-1.07). Conclusion: Our study observed a longitudinal association of road traffic noise exposure with T2D risk, which was stronger among overweight and obese individuals than the lean ones.
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Affiliation(s)
- Lei Zuo
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Xia Chen
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Mingliang Liu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Li Chen
- Department of Medicine, Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, GA, United States
| | - Wenbin Xu
- School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou, Guangdong, China
| | - Haiyan Chen
- Department of Parasitic Disease and Endemic Disease Control and Prevention, Guangzhou Center for Disease Control and Prevention, Guangzhou, China
| | - Shan Dong
- Guangzhou First People’s Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, China
| | - Yuan Wei
- Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China
| | - Liangming Li
- Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China
- School of Sport and Health Sciences, Guangzhou Sport University, Guangzhou, China
| | - Shuang Peng
- Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China
- School of Sport and Health Sciences, Guangzhou Sport University, Guangzhou, China
| | - Guang Hao
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
- Guangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, China
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20
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Kim D, Justice AE, Chittoor G, Blanco E, Burrows R, Graff M, Howard AG, Wang Y, Rohde R, Buchanan VL, Voruganti VS, Almeida M, Peralta J, Lehman DM, Curran JE, Comuzzie AG, Duggirala R, Blangero J, Albala C, Santos JL, Angel B, Lozoff B, Gahagan S, North KE. Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents. Pediatr Res 2022; 92:563-571. [PMID: 34645953 PMCID: PMC9005573 DOI: 10.1038/s41390-021-01729-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/08/2021] [Accepted: 08/17/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.
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Affiliation(s)
- Daeeun Kim
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Anne E Justice
- Department of Population Health Sciences, Geisinger, Danville, PA, USA
| | - Geetha Chittoor
- Department of Population Health Sciences, Geisinger, Danville, PA, USA
| | - Estela Blanco
- Division of Academic General Pediatrics, Child Development and Community Health at the Center for Community Health, University of California at San Diego, San Diego, CA, USA
- Department of Public Health, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Raquel Burrows
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile
| | - Mariaelisa Graff
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Annie Green Howard
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Yujie Wang
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Rebecca Rohde
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Victoria L Buchanan
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - V Saroja Voruganti
- Department of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA
| | - Marcio Almeida
- Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Juan Peralta
- Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Donna M Lehman
- Departments of Medicine and Epidemiology and Biostatistics, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Joanne E Curran
- Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | | | - Ravindranath Duggirala
- Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - John Blangero
- Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Cecilia Albala
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile
| | - José L Santos
- Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Bárbara Angel
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile
| | - Betsy Lozoff
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Sheila Gahagan
- Division of Academic General Pediatrics, Child Development and Community Health at the Center for Community Health, University of California at San Diego, San Diego, CA, USA
| | - Kari E North
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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21
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Zhou J, Yin P, Zhao Q, Hu Z, Wang Y, Ma G, Wu X, Lu L, Shi Y. Electroacupuncture improves follicular development and metabolism and regulates the expression of adiponectin, AMPK and ACC in an obese rat model of polycystic ovary syndrome. Acupunct Med 2022:9645284221107690. [PMID: 35831955 DOI: 10.1177/09645284221107690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and follicular arrest. Electroacupuncture (EA) has been shown to be effective at improving hyperandrogenism and follicular arrest in PCOS; however, its mechanism of action remains to be deciphered. OBJECTIVE In this study, we investigated whether EA improved follicular development in an obese rat model of PCOS and regulated the expression of adiponectin, AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). METHODS EA was administered at CV3, CV4 and ST40. Changes in body weight, paraovarian fat, estrus cycle, ovarian morphology, levels of related hormones, and glucose and lipid metabolism were evaluated. In addition, protein and mRNA expression of adiponectin, AMPK and ACC was measured. RESULTS The body weight and paraovarian fat of rats in the EA group were reduced, while estrus cyclicity and ovarian morphology improved. Levels of free fatty acids, triglycerides, total cholesterol and low-density lipoprotein cholesterol were significantly reduced in the EA group, as well as blood glucose levels. Furthermore, levels of testosterone and luteinizing hormone were reduced in the EA group, while estradiol levels were increased. Protein and mRNA expression of adiponectin, AMPKα1 and liver kinase B1 (LKB1) was found to be increased in the EA group, while protein and mRNA expression of ACC were significantly reduced.Conclusion: Our findings suggest that EA improved follicular development and metabolism and regulated expression levels of adiponectin, AMPKα1, LKB1 and ACC in our obese rat model of PCOS.
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Affiliation(s)
- Jing Zhou
- Department of Acupuncture and Moxibustion, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ping Yin
- Reproduction Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qingyi Zhao
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhihai Hu
- Department of Acupuncture and Moxibustion, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yi Wang
- Department of Acupuncture and Moxibustion, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guizhi Ma
- Department of Acupuncture and Moxibustion, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinyi Wu
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lu Lu
- Reproduction Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yin Shi
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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22
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Wu M, Huang Y, Zhu Q, Zhu X, Xue L, Xiong J, Chen Y, Wu C, Guo Y, Li Y, Wu M, Wang S. Adipose tissue and ovarian aging: Potential mechanism and protective strategies. Ageing Res Rev 2022; 80:101683. [PMID: 35817297 DOI: 10.1016/j.arr.2022.101683] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/29/2022] [Accepted: 07/05/2022] [Indexed: 11/01/2022]
Abstract
Ovarian aging occurs approximately 10 years prior to the natural age-associated functional decline of other organ systems. With the increase of life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Therefore, understanding the causes and molecular mechanisms of ovarian aging is very essential for the inhibition of age-related diseases and the promotion of health and longevity in women. Recently, studies have revealed an association between adipose tissue (AT) and ovarian aging. Alterations in the function and quantity of AT have profound consequences on ovarian function because AT is central for follicular development, lipid metabolism, and hormonal regulation. Moreover, the interplay between AT and the ovary is bidirectional, with ovary-derived signals directly affecting AT biology. In this review, we summarize the current knowledge of the complex molecular mechanisms controlling the crosstalk between the AT and ovarian aging, and further discuss how therapeutic targeting of the AT can delay ovarian aging.
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Affiliation(s)
- Meng Wu
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Yibao Huang
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Qingqing Zhu
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Xiaoran Zhu
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Liru Xue
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Jiaqiang Xiong
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Ying Chen
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Chuqing Wu
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Yican Guo
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Yinuo Li
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China
| | - Mingfu Wu
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China.
| | - Shixuan Wang
- National Clinical Research Center for Obstetrical and Gynecological Diseases; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei 430030, China; Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, Hubei 430030, China.
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23
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Chen P, Jia R, Liu Y, Cao M, Zhou L, Zhao Z. Progress of Adipokines in the Female Reproductive System: A Focus on Polycystic Ovary Syndrome. Front Endocrinol (Lausanne) 2022; 13:881684. [PMID: 35692386 PMCID: PMC9178087 DOI: 10.3389/fendo.2022.881684] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 04/19/2022] [Indexed: 12/16/2022] Open
Abstract
Adipose tissue, one type of loose connective tissue in the human body, maintains the primary task of energy storage. Adipose tissue is not only an energy reservoir but also plays a vital role as the largest endocrine organ of the whole body via releasing a variety of adipokines, which participate in many pathophysiological processes, such as energy metabolism regulation, glucose and lipid metabolism, and inflammation. Polycystic ovary syndrome (PCOS) is a disorder that mainly involves the female reproductive system, affecting women of childbearing age particularly. Insulin resistance (IR) and hyperandrogenemia (HA) have been implicated as a critical link involving the etiology and outcome of PCOS. A great deal of studies has bridged the gap between adipokines (such as Adiponectin, Chemerin, Metrnl, Apelin, Resistin, Visfatin, Leptin, Vaspin, Lipocalin 2, and Omentin) and reproductive fitness. In this review, we will focus on the adipokines' functions on PCOS and come up with some points of view on the basis of current research.
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Affiliation(s)
| | | | | | | | | | - Zhiming Zhao
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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24
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Scott SR, Manczak EM. Metabolic proteins at birth predict early childhood mental health symptoms. Dev Psychobiol 2022; 64:e22248. [PMID: 35191530 DOI: 10.1002/dev.22248] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 11/09/2021] [Accepted: 01/03/2022] [Indexed: 11/09/2022]
Abstract
Child mental health disorders are the leading cause of disability in children and adolescents worldwide. Biological correlates predict psychosocial outcomes throughout human development; however, less is known about metabolic proteins. Drawing from a longitudinal birth cohort study, Born in Bradford (BiB), we examined the role of infant metabolic proteins at birth in predicting early childhood mental health symptoms at 3 and 5 years. We found that higher leptin predicted more prosocial behavior at age 3. Additionally, a higher leptin-to-adiponectin ratio predicted increased total symptom difficulties. At age 5, we found that higher adiponectin predicted a decreased likelihood of being rated by teachers as meeting or exceeding expectations in the domain of "managing feelings and behaviors" and marginally predicted lower competency in "making relationships" on national developmental milestone evaluations. To our knowledge, this is among the first few studies to prospectively predict mental health symptoms from cord blood metabolic proteins, and the first examining this association with a leptin-to-adiponectin ratio. Our results provide support for the possibility that metabolic proteins at birth forecast risk for mental health symptoms in early childhood.
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Affiliation(s)
- Samantha R Scott
- Department of Psychology, University of Denver, Denver, Colorado, USA
| | - Erika M Manczak
- Department of Psychology, University of Denver, Denver, Colorado, USA
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25
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Adiponectin in Osteoarthritis: Pathophysiology, Relationship with Obesity and Presumptive Diagnostic Biomarker Potential. Diagnostics (Basel) 2022; 12:diagnostics12020455. [PMID: 35204546 PMCID: PMC8871474 DOI: 10.3390/diagnostics12020455] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/06/2022] [Accepted: 02/07/2022] [Indexed: 02/01/2023] Open
Abstract
Osteoarthritis (OA) is a multifactorial, irreversible age- and obesity-induced joint degenerative disease, with an increasing incidence in developed countries. With a pathophysiology and etiology that are currently under-investigated, the only available disease-modifying treatment relies solely on total joint arthroplasty, which entails major economic burdens. Recently, the research focus has shifted towards the evaluation of metabolically active mediators secreted by the adipose tissue, which could be potential targets for a better understanding of the mechanisms involved in OA onset and development. Of note, adiponectin has drawn a great deal of attention, since it is the most abundant type of circulating adipokine and has been highly associated with OA occurrence. Thus far, studies have been controversial in establishing whether adiponectin possesses a destructive or protective role in OA development. Therefore, we critically and systematically reviewed, herein, the roles of adiponectin in the pathophysiology of OA, the link between obesity, adiponectin expression and the progression of OA, as well as its potential role as a future biomarker for a more optimized and reliable diagnosis of this degenerative disorder.
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26
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Zhu Y, Wei Y, Duan J, Li J, Zhang R, Sun J, Wang P, Liu Z, Lv J, Wei S, Jiang X, Wang F, Tang Y. The role of leptin in indirectly mediating "somatic anxiety" symptoms in major depressive disorder. Front Psychiatry 2022; 13:757958. [PMID: 35911226 PMCID: PMC9337242 DOI: 10.3389/fpsyt.2022.757958] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 06/28/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Leptin is a multifunctional hormone secreted from adipose tissue, which plays a core role in regulating energy intake and expenditure. Evidence has demonstrated that leptin receptors are located in brain areas involved in emotional processing, and major depressive disorder (MDD) is characterized by dysfunction of emotional processing. Taken together, these features suggest that leptin may play a potential role in the pathophysiology of MDD. However, the precise roles of leptin in modulating depressive symptoms in MDD remain unclear. METHODS Participants [18 drug-naïve MDD patients, 15 unaffected first-degree relatives of MDD patients (FDR-MDD), and 40 healthy controls] completed clinical assessments and provided blood samples for measurement of leptin levels. We evaluated the effect of leptin on clinical status (MDD or FDR-MDD) and symptomatic dimensionalities of MDD using mediation analysis. RESULTS We found that leptin was increased in MDD patients and this only predicted "somatic anxiety" symptoms. Furthermore, leptin was a significant and indirect mediator of the association between clinical status (MDD or FDR-MDD) and "somatic anxiety" symptoms. CONCLUSION Our finding that leptin was a significant and indirect mediator of clinical status (MDD or FDR-MDD) and "somatic anxiety" symptoms suggests that leptin may indirectly affect somatic depressive symptoms in MDD. Our findings may provide a theoretical basis for novel clinical interventions in MDD.
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Affiliation(s)
- Yue Zhu
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yange Wei
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jia Duan
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jianing Li
- China Medical University and Queen's University of Belfast Joint College, China Medical University, Shenyang, China
| | - Ran Zhang
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jiaze Sun
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Pengshuo Wang
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhuang Liu
- School of Public Health, China Medical University, Shenyang, China
| | - Jing Lv
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Psychiatry, Corning Hospital, Shenzhen, China
| | - Shengnan Wei
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiaowei Jiang
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Fei Wang
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yanqing Tang
- Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.,Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Gerontology, The First Affiliated Hospital of China Medical University, Shenyang, China
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27
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Wang Y, Wu L, Yang Z, Xu R, Duan Y, Lin J, Cui X, Fan C, Zhou Y, Bao W, Jin L, Liu Y. Association of body mass index with serum anti-Müllerian hormone and inhibin B levels among 8323 women attending a reproductive medical center: a cross-sectional study. Endocrine 2022; 75:284-292. [PMID: 34363585 DOI: 10.1007/s12020-021-02839-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 07/26/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE To assess the association of body mass index (BMI) with serum anti-Müllerian hormone (AMH) and inhibin B (InB) levels among women attending a reproductive medical center. METHODS We conducted a cross-sectional study of 8323 women (96.4% were Han race) without polycystic ovary syndrome (PCOS) from the reproductive medical center of Tongji Hospital in Wuhan, China for assisted reproductive technology treatment between January 2016 and May 2018. For each participant, BMI and levels of serum AMH and InB were measured at entry by trained clinical technicians. Multivariate linear regression models were used to quantitatively estimate the associations of continuous and categorical BMI with serum AMH and InB levels. RESULTS Each 1 kg/m2 increase in BMI was significantly associated with a 1.02% (95% CI: 0.40, 1.65%) and 3.59% (3.11, 4.06%) reduction in AMH and InB levels, respectively. No departure from linearity was observed for either AMH or InB (both P for nonlinear trend >0.05). Overweight and obesity were significantly associated with a 6.01% (0.70, 11.04%) and 18.64% (2.29, 32.26%) reduction in AMH level, and were significantly associated with a 18.80% (15.23, 22.23%) and a 35.44% (25.47, 44.08%) reduction in InB level, respectively. In addition, the association between BMI and AMH level was significantly stronger among women ≥32 years. CONCLUSIONS BMI was linearly and inversely associated with AMH and InB levels among women without PCOS. Both overweight and obesity were significantly associated with lower AMH and InB levels.
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Affiliation(s)
- Yaqi Wang
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, Guangdong, 510080, China
| | - Li Wu
- Reproductive Medical Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China
| | - Zhengyu Yang
- Melbourne School of Population & Global Health, The University of Melbourne, 207 Bouverie Street, Melbourne, Victoria, 3010, Australia
| | - Ruijun Xu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, Guangdong, 510080, China
| | - Yonggang Duan
- Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, 1 Haiyuan First Road, Shenzhen, Guangdong, 518053, China
| | - Jiajia Lin
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, Guangdong, 510080, China
| | - Xiuqing Cui
- Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Center for Disease Control and Prevention, 35 Zhuodaoquan North Road, Wuhan, Hubei, 430079, China
| | - Chuangang Fan
- Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Center for Disease Control and Prevention, 35 Zhuodaoquan North Road, Wuhan, Hubei, 430079, China
| | - Yun Zhou
- State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, 510120, China
- School of Public Health, Guangzhou Medical University, 1 Xinzao Road, Guangzhou, Guangdong, 511436, China
| | - Wei Bao
- Department of Epidemiology, College of Public Health, University of Iowa, 145 North Riverside Drive, Iowa City, Iowa, 52242, USA
| | - Lei Jin
- Reproductive Medical Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.
| | - Yuewei Liu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, Guangdong, 510080, China.
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28
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Zuo Q, Band S, Kesavadas M, Madak Erdogan Z. Obesity and Postmenopausal Hormone Receptor-positive Breast Cancer: Epidemiology and Mechanisms. Endocrinology 2021; 162:6370080. [PMID: 34519778 DOI: 10.1210/endocr/bqab195] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Indexed: 12/11/2022]
Abstract
Obesity is a potential risk for several cancers, including postmenopausal, hormone dependent breast cancers. In this review, we summarize recent studies on the impact of obesity on postmenopausal women's health and discuss several mechanisms that were proposed to increase the risk of breast carcinogenesis.
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Affiliation(s)
- Qianying Zuo
- Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL, USA
| | - Shoham Band
- Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL, USA
| | - Mrinali Kesavadas
- Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL, USA
| | - Zeynep Madak Erdogan
- Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL, USA
- Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL, USA
- Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL, USA
- Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Urbana, IL, USA
- Department of Biomedical and Translational Sciences, Carle Illinois, College of Medicine, University of Illinois, Urbana-Champaign, Urbana, IL, USA
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T-Cadherin and the Ratio of Its Ligands as Predictors of Carotid Atherosclerosis: A Pilot Study. Biomedicines 2021; 9:biomedicines9101398. [PMID: 34680515 PMCID: PMC8533356 DOI: 10.3390/biomedicines9101398] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 12/27/2022] Open
Abstract
In the cardiovascular system, atherogenic low-density lipoproteins (LDL) and the protective hormone adiponectin bind to the same receptor, T-cadherin. In this study, we tested the hypothesis that the ratio of circulating LDL to high-molecular weight (HMW) adiponectin could predict the development of atherosclerosis. Using enzyme-linked immunosorbent assay, we measured the level of circulating HMW adiponectin in the blood of donors together with ultrasound measuring of intima-media thickness (IMT) of carotid arteries. Single-nucleotide polymorphisms in the T-cadherin gene were identified using polymerase chain reaction. We found that carotid artery IMT is inversely correlated with the level of HMW in male subjects. We also found that the G allele of rs12444338 SNP in the T-cadherin gene correlates with a lower level of circulating T-cadherin and thinner IMT and therefore could be considered as an atheroprotective genotype. Despite our data, we could not provide direct evidence for the initial study hypothesis. However, we did uncover an important correlation between circulating T-cadherin and thinner carotid IMT.
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30
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Prenatal maternal mental health symptoms predict infant leptin at birth. Brain Behav Immun Health 2021; 16:100317. [PMID: 34589807 PMCID: PMC8474689 DOI: 10.1016/j.bbih.2021.100317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 01/03/2023] Open
Abstract
Childhood obesity can be predicted by metabolic signaling at birth. Understanding what exposure factors, such as prenatal mental health, predict metabolic signaling at birth are important for understanding the etiology of childhood metabolic dysregulation. Drawing on data from the Born in Bradford (BiB) multi-ethnic birth cohort in the United Kingdom (N = 2962 dyads), this study examined associations between maternal prenatal mental health symptoms and infant leptin and adiponectin. We tested whether total maternal prenatal symptoms as well as specific symptom subscales forecasted infant cord blood levels of leptin and adiponectin. We found that higher total maternal mental health symptoms and somatic symptoms, specifically, predicted lower infant cord blood leptin. We did not find evidence that maternal prenatal mental health symptoms predicted adiponectin. Together, our findings suggest that maternal mental health symptoms may become biologically embedded through infant metabolic changes via leptin.
Maternal prenatal mental health symptoms predict infant cord blood leptin at birth. Somatic maternal prenatal mental health symptoms predict infant cord blood leptin at birth. Maternal prenatal mental health symptoms do not predict infant cord blood adiponectin at birth. Maternal prenatal mental health may become biologically embedded in infants via leptin.
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31
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The Controversial Role of Adiponectin in Appetite Regulation of Animals. Nutrients 2021; 13:nu13103387. [PMID: 34684387 PMCID: PMC8539471 DOI: 10.3390/nu13103387] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/05/2021] [Accepted: 09/23/2021] [Indexed: 12/20/2022] Open
Abstract
Eating disorders and obesity are important health problems with a widespread global epidemic. Adiponectin (AdipoQ), the most abundant adipokine in the plasma, plays important roles in the regulation of energy homeostasis, glucose metabolism and lipid metabolism. Plasma adiponectin concentration is negatively associated with obesity and binge eating disorder. There is a growing interest in the appetite regulation function of adiponectin. However, the effect of AdipoQ on feeding behavior is controversial and closely related to nutritional status and food composition. In this review, we summarize the literatures about the discovery, structure, tissue distribution, receptors and regulation of nutritional status, and focus on the biological function of adiponectin in the regulation of food intake in the central and peripheral system.
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Kanduc D. From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry. Antibodies (Basel) 2021; 10:36. [PMID: 34698069 PMCID: PMC8544210 DOI: 10.3390/antib10040036] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 08/20/2021] [Accepted: 09/08/2021] [Indexed: 02/07/2023] Open
Abstract
The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike glycoprotein (gp) using public databases. It was found that the SARS-CoV-2 spike gp shares numerous pentapeptides with anti-inflammatory proteins that, when altered, can lead to cytokine storms characterized by diverse disorders such as systemic multiorgan hyperinflammation, macrophage activation syndrome, ferritinemia, endothelial dysfunction, and acute respiratory syndrome. Immunologically, many shared peptides are part of experimentally validated epitopes and are also present in pathogens to which individuals may have been exposed following infections or vaccinal routes and of which the immune system has stored memory. Such an immunologic imprint might trigger powerful anamnestic secondary cross-reactive responses, thus explaining the raging of the cytokine storm that can occur following exposure to SARS-CoV-2. In conclusion, the results support molecular mimicry and the consequent cross-reactivity as a potential mechanism in SARS-CoV-2-induced cytokine storms, and highlight the role of immunological imprinting in determining high-affinity, high-avidity, autoimmune cross-reactions as a pathogenic sequela associated with anti-SARS-CoV-2 vaccines.
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Affiliation(s)
- Darja Kanduc
- Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70125 Bari, Italy
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33
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Ghafoor L, Entezari V, Fallah A, Hajian A. Lipoabdominoplasty and the leptin hormone. Ann Med Surg (Lond) 2021; 68:102633. [PMID: 34386225 PMCID: PMC8346541 DOI: 10.1016/j.amsu.2021.102633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/26/2021] [Accepted: 07/26/2021] [Indexed: 11/28/2022] Open
Abstract
Background Obesity contributes to a chronic disease with lethal complications. Leptin as an adiponectin interacts with fat metabolism. Surgical extra fat resection is an interventional approach to control obesity. We aimed to evaluate how body contouring surgery would influence on leptin plasma level. Methods Females candidate for body contouring surgery were allocated in to two groups included abdominal wall liposuction alone and in combination with abdominoplasty from 2018 to 2020. Demographic data was registered. Serum plasma level of leptin with the ELISA method was measured on the day before the operation and also after 3, 6, and 12 months after surgery with 8 h fasting prior to blood sampling. Finally the amounts of resected fat, type of surgical approach, and plasma level of leptin were analyzed. Results Total 124 females with mean age of 37 ± 10.1 years underwent abdominal wall liposuction (58%) and liposuction + abdominoplasty (42%) respectively. Mean weight and BMI significantly decreased postoperatively for both groups (p < 0.01). Although in both groups leptin concentration was higher in all triple blood sampling following operation in compared to preoperative measurement, changes were not significantly considerable (p = 0.6). Coefficient of correlation between amounts of resected fat and plasma level of leptin was directly positive and calculated 0.4 (p = 0.03). Conclusion Leptin interacts independently from abdominal wall contouring surgery. However it could be a marker for amounts of resected fat after operation.
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Affiliation(s)
- Leila Ghafoor
- Department of General Surgery, Kashan University of Medical Sciences, Kashan, Iran
| | - Vahid Entezari
- Department of General Surgery, Kashan University of Medical Sciences, Kashan, Iran
| | - Atefe Fallah
- Kashan University of Medical Sciences, Kashan, Iran
| | - Abbas Hajian
- Department of General Surgery, Kashan University of Medical Sciences, Kashan, Iran
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Kabalyk MA, Nevzorova VA. Molecular and Cellular Mechanisms of Osteoarthritis in Experimental Arterial Hypertension and Hyperlipidemia. ADVANCES IN GERONTOLOGY 2021. [DOI: 10.1134/s2079057021020065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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35
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Sasaki T, Abe Y, Takayama M, Adachi T, Okano H, Hirose N, Arai Y. Association among extracellular superoxide dismutase genotype, plasma concentration, and comorbidity in the very old and centenarians. Sci Rep 2021; 11:8539. [PMID: 33879836 PMCID: PMC8058336 DOI: 10.1038/s41598-021-87982-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 04/07/2021] [Indexed: 12/30/2022] Open
Abstract
Superoxide dismutase 3 (SOD3), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85–99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98–3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39–0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.
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Affiliation(s)
- Takashi Sasaki
- Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Yukiko Abe
- Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Michiyo Takayama
- Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.,Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tetsuo Adachi
- Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
| | - Hideyuki Okano
- Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.,Department of Physiology, Keio University School of Medicine, Tokyo, Japan
| | - Nobuyoshi Hirose
- Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yasumichi Arai
- Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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36
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Zhou Y, Yang Y, Zhou T, Li B, Wang Z. Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity. Aging Dis 2021; 12:597-613. [PMID: 33815885 PMCID: PMC7990371 DOI: 10.14336/ad.2020.0919] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 09/13/2020] [Indexed: 12/14/2022] Open
Abstract
In recent decades, the incidence and diagnosis of thyroid cancer have risen dramatically, and thyroid cancer has now become the most common endocrine cancer in the world. The onset of thyroid cancer is insidious, and its progression is slow and difficult to detect. Therefore, early prevention and treatment have important strategic significance. Moreover, an in-depth exploration of the pathogenesis of thyroid cancer is key to early prevention and treatment. Substantial evidence supports obesity as an independent risk factor for thyroid cancer. Adipose tissue dysfunction in the obese state is accompanied by dysregulation of a variety of adipocytokines. Adiponectin (APN) is one of the most pivotal adipocytokines, and its connection with obesity and obesity-related disease has gradually become a hot topic in research. Recently, the association between APN and thyroid cancer has received increasing attention. The purpose of this review is to systematically review previous studies, give prominence to APN, focus on the relationship between APN, obesity and thyroid cancer, and uncover the underlying pathogenic mechanisms.
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Affiliation(s)
- Yuanyuan Zhou
- 1Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, China.,2Department of Endocrinology and Metabolism, Sixth Affiliated Hospital of Kunming Medical University, The People's Hospital of Yuxi City, Yuxi, China
| | - Ying Yang
- 1Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Taicheng Zhou
- 1Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Bai Li
- 3School of Medicine, Yunnan University, Kunming, China
| | - Zhanjian Wang
- 4Department of Endocrinology and Metabolism, The Third Hospital of Hebei Medical University, Shijiazhuang, China
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Luo L, Li J, Wu Y, Qiao J, Fang H. Adiponectin, but Not TGF-β1, CTGF, IL-6 or TNF-α, May Be a Potential Anti-Inflammation and Anti-Fibrosis Factor in Keloid. J Inflamm Res 2021; 14:907-916. [PMID: 33758530 PMCID: PMC7981148 DOI: 10.2147/jir.s301971] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 02/25/2021] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Numerous studies have elucidated adiponectin as a negative impact on inflammation and tissue fibrosis. However, little is known about the relevance between adiponectin and inflammatory factors in keloid. METHODS To clarify whether adiponectin plays a role in the inflammation and fibrosis of keloid, 50 patients with keloid and 50 healthy subjects were enrolled, We examined the serum and mRNA expression levels of adiponectin, TGF-β1, CTGF, IL-6 and TNF-α in normal skin tissues and keloid tissues by ELISA and qPCR, respectively. Correlation analysis between serum concentration of adiponectin with Vancouver Scar Scale (VSS) scores and the age of patients with keloid was evaluated, and the adiponectin concentrations in patients with keloid between different genders were measured. We further examined the effects of adiponectin on TGF-β1 mediated expression of collagen I, FN and MMP-1 in normal fibroblasts (NFs) and keloid fibroblasts (KFs). RESULTS We discovered that lower serum concentration and mRNA expression of adiponectin, but higher TGF-β1, CTGF, IL-6 and TNF-α levels were measured in patients with keloid compared with those in normal controls. Furthermore, there was a strong inverse correlation between the serum adiponectin levels and VSS scores in patients with keloid, but not in ages, and there was no statistically difference between different genders. Moreover, adiponectin attenuated TGF-β1 mediated expression of collagen I and FN, and upregulated the expression level of MMP-1 in KFs, but not in NFs. In addition, the inhibitory effect of adiponectin on TGF-β1 was attenuated by AMPK inhibitor Compound C, but not PI3K/Akt inhibitor LY294002. DISCUSSION Adiponectin may exert an anti-inflammation and anti-fibrosis role in the development of keloid. One of the underlying mechanisms may be the activation of the AMPK signaling pathway.
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Affiliation(s)
- Limin Luo
- Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China
| | - Jun Li
- Department of Cardiology, The First Affiliated Hospital of Zhejiang University, Hangzhou, 310003, People’s Republic of China
| | - Yuran Wu
- Department of Dermatology, Dongfeng General Hospital, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China
| | - Jianjun Qiao
- Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China
| | - Hong Fang
- Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China
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Thappa DM, Chandrashekar L, Rajappa M, Usha R, Muthupandi K, Mohanraj PS, Munisamy M, Singh N. Assessment of Patients with Periorbital Melanosis for Hyperinsulinemia and Insulin Resistance. Indian Dermatol Online J 2021; 12:244-249. [PMID: 33959520 PMCID: PMC8088194 DOI: 10.4103/idoj.idoj_491_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 09/02/2020] [Accepted: 10/21/2020] [Indexed: 11/12/2022] Open
Abstract
Background: Periorbital melanosis (PM) is one of the most common dermatological condition seen in routine practice. Several cutaneous markers such as acanthosis nigricans have been associated with insulin resistance (IR). However, the association of PM with IR needs to be substantiated. Objective: The objective of the study is to evaluate the association of circulating adipokines and IR with PM. Materials and Methods: In this cross-sectional study, we recruited 100 patients with PM and 100 age- and gender-matched healthy controls. The serum levels of leptin, adiponectin, fasting glucose, fasting insulin, insulin-like growth factor-1 (IGF-1), homeostatic model assessment of insulin resistance (HOMA-IR), and leptin: adiponectin ratio (L/A ratio) were assayed. Results: The serum levels of leptin, fasting glucose, fasting insulin, HOMA-IR, L/A ratio were significantly higher in patients with PM as compared to controls. The serum levels of adiponectin were significantly lower in cases as compared to controls. On multivariate regression analysis, leptin, adiponectin, and HOMA-IR were found to be significant, even after adjusting for BMI, blood pressure and LDL and HDL cholesterol. Conclusion: Our findings suggest that patients with PM have hyperinsulinemia, IR, and elevated L/A ratio. PM as a marker of IR in adults may help in identifying patients early and thus aid in the early prevention and management of the disease.
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Affiliation(s)
- Devinder M Thappa
- Department of Dermatology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - Laxmisha Chandrashekar
- Department of Dermatology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - Medha Rajappa
- Department of Biochemistry, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - R Usha
- Department of Dermatology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - K Muthupandi
- Department of Biochemistry, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - Palani S Mohanraj
- Department of Biochemistry, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - Malathi Munisamy
- Department of Dermatology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - Nidhi Singh
- Department of Dermatology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
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Uddin MS, Rahman MM, Sufian MA, Jeandet P, Ashraf GM, Bin-Jumah MN, Mousa SA, Abdel-Daim MM, Akhtar MF, Saleem A, Amran MS. Exploring the New Horizon of AdipoQ in Obesity-Related Alzheimer's Dementia. Front Physiol 2021; 11:567678. [PMID: 33584324 PMCID: PMC7873563 DOI: 10.3389/fphys.2020.567678] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022] Open
Abstract
Alzheimer's disease (AD) is the most common form of dementia, which causes abnormalities in learning, thinking, memory, as well as behavior. Generally, symptoms of AD develop gradually and aggravate over time, and consequently severely interfere with daily activities. Furthermore, obesity is one of the common risk factors for dementia. Dysregulation of adipokine and adipocyte dysfunction are assumed to be accountable for the high risk of obesity in people that develop many related disorders such as AD. Moreover, it has been observed that the dysfunction of adipose is connected with changes in brain metabolism, brain atrophy, cognitive decline, impaired mood, neuroinflammation, impaired insulin signaling, and neuronal dysfunction in people with obesity. Conversely, the pathological mechanisms, as well as the molecular players which are involved in this association, have been unclear until now. In this article, we discuss the impact of adiponectin (AdipoQ) on obesity-related Alzheimer's dementia.
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Affiliation(s)
- Md. Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
| | - Md. Motiar Rahman
- Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China
| | - Mohammad Abu Sufian
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
| | - Philippe Jeandet
- Research Unit, Induced Resistance and Plant Bioprotection, EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, Reims Cedex, France
| | - Ghulam Md. Ashraf
- Pre-clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - May N. Bin-Jumah
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Shaker A. Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, New York, NY, United States
| | - Mohamed M. Abdel-Daim
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan
| | - Ammara Saleem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Md. Shah Amran
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
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Sodhi RK, Singh R, Bansal Y, Bishnoi M, Parhar I, Kuhad A, Soga T. Intersections in Neuropsychiatric and Metabolic Disorders: Possible Role of TRPA1 Channels. Front Endocrinol (Lausanne) 2021; 12:771575. [PMID: 34912298 PMCID: PMC8666658 DOI: 10.3389/fendo.2021.771575] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 11/04/2021] [Indexed: 11/25/2022] Open
Abstract
Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients' monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs.
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Affiliation(s)
- Rupinder Kaur Sodhi
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, University Grants Commission, Center of Advanced Studies (UGC-CAS), Panjab University, Chandigarh, India
| | - Raghunath Singh
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Yashika Bansal
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Mahendra Bishnoi
- TR(i)P for Health Laboratory, Centre of Excellence in Functional Foods, Department of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute (NABI), Punjab, India
| | - Ishwar Parhar
- Brain Research Institute Monash Sunway (BRIMS), Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Anurag Kuhad
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, University Grants Commission, Center of Advanced Studies (UGC-CAS), Panjab University, Chandigarh, India
- *Correspondence: Anurag Kuhad, ; Tomoko Soga,
| | - Tomoko Soga
- Brain Research Institute Monash Sunway (BRIMS), Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Bandar Sunway, Malaysia
- *Correspondence: Anurag Kuhad, ; Tomoko Soga,
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Bluher A, Kawai K, Wang A, Stiles D, Licameli G. Obesity as a Possible Risk Factor for Pediatric Sensorineural Hearing Loss. Laryngoscope 2020; 131:1416-1419. [PMID: 33264432 DOI: 10.1002/lary.29289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/12/2020] [Accepted: 11/16/2020] [Indexed: 11/10/2022]
Abstract
OBJECTIVES/HYPOTHESIS Childhood hearing loss impacts linguistic, academic, social, and psychologic development, and may have lasting implications for future workforce performance. Current evidence for obesity as a pediatric sensorineural hearing loss (SNHL) risk factor is intriguing but equivocal. We hypothesized that obesity is associated with a higher risk of SNHL. We additionally examined whether underweight is associated with a higher risk of SNHL. STUDY DESIGN Retrospective database review. METHODS A single-institution audiologic database from 2015 to 2020 was queried for audiograms with type-A tympanograms from children aged 5 to 18 years old. Comorbidities known to be associated with hearing loss were excluded. We then examined both for sub-clinical (≥15 dB) high- or low-frequency hearing loss, and for clinical (≥21 dB) hearing loss, with the aim of examining the association between obesity and SNHL. Multivariable logistic regression was performed to adjust for age, gender, diabetes mellitus, attention deficit hyperactivity disorder, and autism. RESULTS A total of 3,142 children were included. Obesity was not associated with risk of SNHL (adjusted OR 0.82; 95% CI: 0.60, 1.12). Underweight children had a higher risk of SNHL than normal weight children (adjusted OR 1.78; 95% CI: 1.08, 2.95). Autism was significantly associated with increased risk of sub-clinical SNHL only (adjusted OR 2.00; 95% CI 1.34, 2.98). CONCLUSIONS No association was found between obesity and pediatric SNHL. Underweight children may represent a higher-risk population for SNHL. There appears to be an increasing risk of SNHL as children approach adolescence. Further study of systemic risk factors for SNHL is indicated. LEVEL OF EVIDENCE 3 Laryngoscope, 131:1416-1419, 2021.
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Affiliation(s)
- Andrew Bluher
- Department of Otolaryngology and Communication Enhancement, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts, U.S.A
| | - Kosuke Kawai
- Department of Otolaryngology and Communication Enhancement, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts, U.S.A
| | - Alicia Wang
- Department of Otolaryngology and Communication Enhancement, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts, U.S.A
| | - Derek Stiles
- Department of Otolaryngology and Communication Enhancement, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts, U.S.A
| | - Greg Licameli
- Department of Otolaryngology and Communication Enhancement, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts, U.S.A
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Recinella L, Orlando G, Ferrante C, Chiavaroli A, Brunetti L, Leone S. Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases. Front Physiol 2020; 11:578966. [PMID: 33192583 PMCID: PMC7662468 DOI: 10.3389/fphys.2020.578966] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/14/2020] [Indexed: 12/11/2022] Open
Abstract
Besides its role as an energy storage organ, adipose tissue can be viewed as a dynamic and complex endocrine organ, which produces and secretes several adipokines, including hormones, cytokines, extracellular matrix (ECM) proteins, and growth and vasoactive factors. A wide body of evidence showed that adipokines play a critical role in various biological and physiological functions, among which feeding modulation, inflammatory and immune function, glucose and lipid metabolism, and blood pressure control. The aim of this review is to summarize the effects of several adipokines, including leptin, diponectin, resistin, chemerin, lipocalin-2 (LCN2), vaspin, omentin, follistatin-like 1 (FSTL1), secreted protein acidic and rich in cysteine (SPARC), secreted frizzled-related protein 5 (SFRP5), C1q/TNF-related proteins (CTRPs), family with sequence similarity to 19 member A5 (FAM19A5), wingless-type inducible signaling pathway protein-1 (WISP1), progranulin (PGRN), nesfatin-1 (nesfatin), visfatin/PBEF/NAMPT, apelin, retinol binding protein 4 (RPB4), and plasminogen activator inhibitor-1 (PAI-1) in the regulation of insulin resistance and vascular function, as well as many aspects of inflammation and immunity and their potential role in managing obesity-associated diseases, including metabolic, osteoarticular, and cardiovascular diseases.
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Affiliation(s)
| | | | | | | | - Luigi Brunetti
- Department of Pharmacy, Gabriele d’Annunzio University, Chieti, Italy
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Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute? Nutrients 2020; 12:nu12113310. [PMID: 33137934 PMCID: PMC7692749 DOI: 10.3390/nu12113310] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/23/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023] Open
Abstract
The evolution of obesity and its resulting comorbidities differs depending upon the age of the subject. The dramatic rise in childhood obesity has resulted in specific needs in defining obesity-associated entities with this disease. Indeed, even the definition of obesity differs for pediatric patients from that employed in adults. Regardless of age, one of the earliest metabolic complications observed in obesity involves perturbations in glucose metabolism that can eventually lead to type 2 diabetes. In children, the incidence of type 2 diabetes is infrequent compared to that observed in adults, even with the same degree of obesity. In contrast, insulin resistance is reported to be frequently observed in children and adolescents with obesity. As this condition can be prerequisite to further metabolic complications, identification of biological markers as predictive risk factors would be of tremendous clinical utility. Analysis of obesity-induced modifications of the adipokine profile has been one classic approach in the identification of biomarkers. Recent studies emphasize the utility of metabolomics in the analysis of metabolic characteristics in children with obesity with or without insulin resistance. These studies have been performed with targeted or untargeted approaches, employing different methodologies. This review summarizes some of the advances in this field while emphasizing the importance of the different techniques employed.
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Effects of the CB1 Receptor Antagonists AM6545 and AM4113 on Insulin Resistance in a High-Fructose High-Salt Rat Model of Metabolic Syndrome. ACTA ACUST UNITED AC 2020; 56:medicina56110573. [PMID: 33138155 PMCID: PMC7692885 DOI: 10.3390/medicina56110573] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 10/22/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023]
Abstract
Background and Objectives: Insulin resistance (IR) is a serious condition leading to development of diabetes and cardiovascular complications. Hyper-activation of cannabinoid receptors-1 (CB1) has been linked to the development of metabolic disorders such as IR. Therefore, the effect of blocking CB1 on the development of IR was investigated in the present study. Materials and Methods: A 12-week high-fructose/high-salt feeding model of metabolic syndrome was used to induce IR in male Wistar rats. For this purpose, two different CB1-antagonists were synthesized and administered to the rats during the final four weeks of the study, AM6545, the peripheral neutral antagonist and AM4113, the central neutral antagonist. Results: High-fructose/salt feeding for 12 weeks led to development of IR while both AM6545 and AM4113, administered in the last 4 weeks, significantly inhibited IR. This was correlated with increased animal body weight wherein both AM6545 and AM4113 decreased body weight in IR animals but with loss of IR/body weight correlation. While IR animals showed significant elevations in serum cholesterol and triglycerides with no direct correlation with IR, both AM6545 and AM4113 inhibited these elevations, with direct IR/cholesterol correlation in case of AM6545. IR animals had elevated serum uric acid, which was reduced by both AM6545 and AM4113. In addition, IR animals had decreased adiponectin levels and elevated liver TNFα content with strong IR/adiponectin and IR/TNFα correlations. AM6545 inhibited the decreased adiponectin and the increased TNFα levels and retained the strong IR/adiponectin correlation. However, AM4113 inhibited the decreased adiponectin and the increased TNFα levels, but with loss of IR/adiponectin and IR/TNFα correlations. Conclusions: Both CB1 neutral antagonists alleviated IR peripherally, and exerted similar effects on rats with metabolic syndrome. They also displayed anti-dyslipidemic, anti-hyperurecemic and anti-inflammatory effects. Overall, these results should assist in the development of CB1 neutral antagonists with improved safety profiles for managing metabolic disorders.
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Wei R, Han C, Deng D, Ye F, Gan X, Liu H, Li L, Xu H, Wei S. Research progress into the physiological changes in metabolic pathways in waterfowl with hepatic steatosis. Br Poult Sci 2020; 62:118-124. [DOI: 10.1080/00071668.2020.1812527] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- R. Wei
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - C. Han
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - D. Deng
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - F. Ye
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - X. Gan
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - H. Liu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - L. Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - H. Xu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
| | - S. Wei
- College of Life Science, Sichuan Agricultural University, Ya’an, Sichuan, P.R. China
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Jaswa EG, Rios JS, Cedars MI, Santoro NF, Pavone MEG, Legro RS, Huddleston HG. Increased Body Mass Index Is Associated With A Nondilutional Reduction in Antimüllerian Hormone. J Clin Endocrinol Metab 2020; 105:dgaa436. [PMID: 32756952 PMCID: PMC7448935 DOI: 10.1210/clinem/dgaa436] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 07/02/2020] [Indexed: 12/15/2022]
Abstract
CONTEXT Controversy exists regarding if and how body mass index (BMI) impacts antimüllerian hormone (AMH) in women with and without polycystic ovary syndrome (PCOS). Understanding the BMI-AMH relationship has critical implications for clinical interpretation of laboratory values and could illuminate underlying ovarian physiology. OBJECTIVE To test the hypotheses that (1) BMI is associated with reduced AMH in PCOS and ovulatory controls (OVAs) and (2) the reduction in AMH is not accounted for by dilutional effects. DESIGN/SETTING Multicenter cohort. PARTICIPANTS Women aged 25 to 40 years from 2 clinical populations: 640 with PCOS, 921 women as OVAs. MAIN OUTCOME MEASURES Ovarian reserve indices: AMH, antral follicle count (AFC), and AMH to AFC ratio (AMH/AFC) as a marker of per-follicle AMH production. RESULTS In both cohorts, increasing BMI and waist circumference were associated with reductions in AMH and AMH/AFC, after adjusting for age, race, smoking, and site in multivariate regression models. Increasing BMI was associated with reduced AFC in PCOS but not OVAs. Body surface area (BSA), which unlike BMI is strongly proportional to plasma volume, was added to investigate a potential dilutive effect of body size on AMH concentrations. After controlling for BSA, BMI retained independent associations with AMH in both cohorts; BSA no longer associated with AMH. CONCLUSIONS In an adjusted analysis, BMI, but not BSA, was associated with reduced AMH; these data do not support a role for hemodilution in mediating the relationship between increased body size and reduced AMH. Decreased AMH production by the follicle unit may be responsible for reduced AMH with increasing BMI.
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Affiliation(s)
- Eleni Greenwood Jaswa
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, California
| | - Julie S Rios
- Department of Obstetrics & Gynecology, University of Cincinnati, Cincinnati, Ohio
| | - Marcelle I Cedars
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, California
| | - Nanette F Santoro
- Department of Obstetrics & Gynecology, University of Colorado, Denver, Colorado
| | - Mary Ellen G Pavone
- Department of Obstetrics & Gynecology, Northwestern University, Chicago, Illinois
| | - Richard S Legro
- Department of Obstetrics & Gynecology, Pennsylvania State University, Hershey, Pennsylvania
| | - Heather G Huddleston
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, California
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Brunetti G, Faienza MF, Piacente L, Storlino G, Oranger A, D’Amato G, De Filippo G, Colucci S, Grano M. Shedding "LIGHT" on the Link between Bone and Fat in Obese Children and Adolescents. Int J Mol Sci 2020; 21:E4739. [PMID: 32635185 PMCID: PMC7370129 DOI: 10.3390/ijms21134739] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 06/30/2020] [Accepted: 07/01/2020] [Indexed: 12/15/2022] Open
Abstract
Obesity may affect bone health, but literature reports are contradictory about the correlation of body mass index (BMI) and bone markers. LIGHT, one of the immunostimulatory cytokines regulating the homeostasis of bone and adipose tissue, could be involved in obesity. The study involved 111 obese subjects (12.21 ± 3.71 years) and 45 controls. Patients underwent the evaluation of bone status by quantitative ultrasonography (QUS). LIGHT amounts were evaluated in sera by ELISA, whereas its expression on peripheral blood cells was evaluated by flow cytometry. Osteoclastogenesis was performed by culturing peripheral blood mononuclear cells (PBMCs) with or without anti-LIGHT antibodies. Obese patients showed significant high BMI-standard deviation score (SDS), weight-SDS, and Homeostatic model assessment for insulin resistance (HOMA-IR) that negatively correlated with the reduced Amplitude Dependent Speed of Sound (AD-SoS)-Z-score and Bone Transmission Time (BTT-Z)-score. They displayed significantly higher serum levels of LIGHT compared with controls (497.30 ± 363.45 pg/mL vs. 186.06 ± 101.41 pg/mL, p < 0.001). LIGHT expression on monocytes, CD3+-T-cells, and neutrophils was also higher in obese patients than in the controls. Finally, in PBMC cultures, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition. Our study highlighted the high serum levels of LIGHT in obese children and adolescents, and its relationship with both the grade of obesity and bone impairment.
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Affiliation(s)
- Giacomina Brunetti
- Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy;
| | - Maria Felicia Faienza
- Department of Biomedical Science and Human Oncology, Paediatric Unit, University of Bari, 70100 Bari, Italy; (M.F.F.); (L.P.)
| | - Laura Piacente
- Department of Biomedical Science and Human Oncology, Paediatric Unit, University of Bari, 70100 Bari, Italy; (M.F.F.); (L.P.)
| | - Giuseppina Storlino
- Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy; (G.S.); (A.O.); (M.G.)
| | - Angela Oranger
- Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy; (G.S.); (A.O.); (M.G.)
| | - Gabriele D’Amato
- Neonatal Intensive Care Unit, Di Venere Hospital, 70131 Bari, Italy;
| | - Gianpaolo De Filippo
- Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique, 75019 Paris, France;
| | - Silvia Colucci
- Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy;
| | - Maria Grano
- Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy; (G.S.); (A.O.); (M.G.)
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Pathak MP, Das A, Patowary P, Chattopadhyay P. Contentious role of 'Good Adiponectin' in pulmonary and cardiovascular diseases: Is adiponectin directed therapy a boon or a bane? Biochimie 2020; 175:106-119. [PMID: 32473183 DOI: 10.1016/j.biochi.2020.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/27/2020] [Accepted: 05/12/2020] [Indexed: 11/24/2022]
Abstract
After two decades of its discovery, numerous facts of adiponectin (APN) biology has been uncovered, yet, APN remains an elusive adipokine. Findings from clinical studies and animal models established APN's ameliorative role in cardiovascular disease (CVD) and pulmonary disease (PD) but the same condition is prognostic for mortality in the same set of patients which cornered APN towards a dubious state. A repertoire of mechanisms associated with the positive association of APN in both lean/cachectic or obese CVD and PD patients from past publications are evaluated. Newer pharmacological agent may be explored to regulate elevated blood APN concentration in COPD or CHF patients whereas administration of recombinant APN as well as growth hormone may augment blood APN concentration in obese subjects associated with low blood and intracellular APN concentration. However, some APN directed therapy in clinical as well as in pre-clinical setup has pronounced some contentious effects. After reviewing the mechanisms of the contentious role of APN functioning in pathologic conditions of CVD and PD in both lean and obese conditions, the authors came to conclusion that APN directed therapy may be utilized with caution keeping in mind the different age group, sex and the different CVD as well as pulmonary diseases they are suffering from.
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Affiliation(s)
- Manash Pratim Pathak
- Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, India; Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
| | - Aparoop Das
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
| | - Pompy Patowary
- Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, India; Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
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Zhu J, Liu C, Jia J, Zhang C, Yuan W, Leng H, Xu Y, Song C. Short-term caloric restriction induced bone loss in both axial and appendicular bones by increasing adiponectin. Ann N Y Acad Sci 2020; 1474:47-60. [PMID: 32469430 DOI: 10.1111/nyas.14380] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/30/2020] [Accepted: 05/05/2020] [Indexed: 12/13/2022]
Abstract
Caloric restriction (CR) is well described and has received extensive attention for its multiple benefits, including longevity and stress resistance. However, some studies have shown that CR negatively influences bone, although a mechanism hasn't been provided. Adiponectin, an adipocyte-derived hormone, can affect bone metabolism by various pathways. To explore the role of adiponectin in short-term CR on bone, we tested the effect of short-term CR on limb bones (tibia and femur) and lumbar vertebral bodies of young C57BL/6 wild-type (WT) and adiponectin-deficient (Apn-/- ) mice. Two dietary regimes, ad libitum (AL) and CR (70% of the AL diet), were used. Dietary restriction led to increased serum adiponectin in WT mice, while bone mineral density, bone microarchitecture, and biomechanical outcomes of limb bone and vertebrae were decreased. In contrast, bone length, microarchitecture, and biomechanical outcomes were not impaired after CR in Apn-/- mice. Furthermore, CR increased adiponectin expression both in white adipose tissue and bone marrow adipose tissue in young WT mice. Histology analysis showed that expansion of bone marrow adipose tissue after CR in Apn-/- mice was impaired compared with WT mice. These results suggest that increased adiponectin induced by short-term CR may negatively influence bones.
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Affiliation(s)
- Junxiong Zhu
- Department of Orthopedics, Peking University Third Hospital, Beijing, China
| | - Can Liu
- Department of Orthopedics, Peking University Third Hospital, Beijing, China
| | - Jialin Jia
- Department of Orthopedics, Peking University Third Hospital, Beijing, China
| | - Chenggui Zhang
- Department of Orthopedics, Peking University Third Hospital, Beijing, China
| | - Wanqiong Yuan
- Department of Orthopedics, Peking University Third Hospital, Beijing, China
| | - Huijie Leng
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.,Beijing Key Laboratory of Spinal Diseases, Beijing, China
| | - Yingsheng Xu
- Department of Neurology, Peking University Third Hospital, Beijing, China
| | - Chunli Song
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.,Beijing Key Laboratory of Spinal Diseases, Beijing, China
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Song SH, Oh TR, Choi HS, Kim CS, Ma SK, Oh KH, Ahn C, Kim SW, Bae EH. High serum adiponectin as a biomarker of renal dysfunction: Results from the KNOW-CKD study. Sci Rep 2020; 10:5598. [PMID: 32221363 PMCID: PMC7101406 DOI: 10.1038/s41598-020-62465-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 03/05/2020] [Indexed: 02/08/2023] Open
Abstract
High serum adiponectin is noted in several conditions of chronic kidney disease (CKD) and is a predictor for end stage renal disease. However, the relationship between adiponectin level and renal disease progression is not well established. This study aimed to determine the relationship between serum adiponectin levels and CKD progression. This prospective longitudinal study included 2238 patients from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease. Patients were divided into quartiles according to their serum adiponectin level. Composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate (eGFR) during the follow-up period. A cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and serum adiponectin levels. Serum adiponectin level was inversely associated with eGFR (p < 0.001) and positively correlated with urine albumin-creatinine ratio. The highest quartile of serum adiponectin was associated with an increased risk of adverse renal outomes (HR, 1.39; 95%CI, 1.05-1.84; p=0.021). On time-dependent receiver operating characteristic curve analysis, predictive ability of adiponectin for renal outcomes disappeared after adjusting for eGFR. Therefore, serum adiponectin may be a biomarker of renal dysfunction rather than a true risk factor in CKD progression.
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Affiliation(s)
- Su Hyun Song
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Tae Ryom Oh
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hong Sang Choi
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Chang Seong Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Seong Kwon Ma
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Kook Hwan Oh
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Soo Wan Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
| | - Eun Hui Bae
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
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