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Chiu YH, Chou WL, Ko MC, Liao JC, Huang TH. Curcumin mitigates obesity-driven dysbiosis and liver steatosis while promoting browning and thermogenesis in white adipose tissue of high-fat diet-fed mice. J Nutr Biochem 2025; 143:109920. [PMID: 40239823 DOI: 10.1016/j.jnutbio.2025.109920] [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: 11/10/2024] [Revised: 04/02/2025] [Accepted: 04/09/2025] [Indexed: 04/18/2025]
Abstract
Curcumin, recognized for its antioxidant and anti-inflammatory properties, is a promising dietary supplement for liver protection. However, its role in preventing obesity-induced hepatic steatosis is not fully understood. This study aims to show that curcumin mitigates hepatic steatosis and promotes browning and thermogenesis in white adipose tissue (WAT) under obesity. Male C57BL/6 mice were assigned to four groups: standard diet (STD), STD supplemented with 100 mg/kg curcumin, high-fat diet (HFD), or HFD supplemented with 100 mg/kg curcumin, administered for 4 weeks. Compared to STD mice, HFD-fed mice exhibited significantly greater body weight, epididymal fat mass, liver weight, postprandial blood glucose (PBG), insulin, and plasma/hepatic alanine aminotransferase (ALT) and triglyceride (TG) levels, alongside an inflammatory response and macrophage infiltration. Additionally, HFD-fed mice showed reduced adiponectin, adiponectin receptor-1, and PI3K/AKT phosphorylation in liver tissue. Except for liver weight, these effects were reversed in curcumin-treated HFD mice. Curcumin inhibited adipocyte hypertrophy and elevated the expression of PGC-1α, PPARγ, and UCP-1 proteins, as well as Zic1, Prdm16, Tnfrsf9, and Tmem26 genes in epididymal fat pads (EFPs). It also significantly altered gut microbiota composition, reducing pro-inflammatory bacteria such as Helicobacter, Oscillospira, Parabacteroides, and Alistipes, thereby alleviating intestinal dysbiosis and improving obesity-related metabolic parameters. In conclusion, curcumin's protective effects against hepatic steatosis and adiposity in HFD-fed mice stem from its ability to upregulate adiponectin, enhance insulin signaling, promote WAT browning, increase thermogenesis, and modulate intestinal dysbiosis.
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Affiliation(s)
- Yi-Han Chiu
- Department of Microbiology, Soochow University, Taipei, Taiwan
| | - Wei-Ling Chou
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Min-Chi Ko
- Department of Microbiology, Soochow University, Taipei, Taiwan
| | - Jun-Cheng Liao
- Department of Microbiology, Soochow University, Taipei, Taiwan
| | - Tse-Hung Huang
- Department of Traditional Chinese Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Chemical Engineering and Graduate Institute of Biochemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan; Department of Traditional Chinese Medicine, Xiamen Chang Gung Hospital, Xiamen, China.
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Menzies‐Gow NJ, Knowles EJ. Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. J Vet Pharmacol Ther 2025; 48 Suppl 1:31-40. [PMID: 38984777 PMCID: PMC11736997 DOI: 10.1111/jvp.13470] [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: 03/01/2024] [Revised: 05/28/2024] [Accepted: 06/26/2024] [Indexed: 07/11/2024]
Abstract
Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.
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Affiliation(s)
| | - Edward J. Knowles
- Department of Clinical Science and ServicesRoyal Veterinary CollegeHertfordshireUK
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Takahashi F, Okada H, Hashimoto Y, Kurogi K, Murata H, Ito M, Fukui M. Association between alcohol consumption and incidence of type 2 diabetes in middle-aged Japanese from Panasonic cohort study 12. Sci Rep 2024; 14:20315. [PMID: 39223288 PMCID: PMC11369267 DOI: 10.1038/s41598-024-71383-6] [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: 01/22/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open
Abstract
This retrospective cohort study aimed to investigate the association between alcohol consumption and the onset of type 2 diabetes in middle-aged Japanese individuals. Participants were aged 40 and above from Panasonic Corporation, Osaka, Japan's medical health checkup program from 2008 to 2021. Alcohol consumption was calculated by converting the quantity consumed into daily ethanol consumption. We assessed the association between alcohol consumption and the onset of type 2 diabetes using Cox regression analysis. The total and median follow-up duration was 13 years and 7 (3-13) years (748,090 person-years). Among 102,802 participants, 7,510 participants (7.3%) developed type 2 diabetes during the study period. Alcohol consumption at the level of 0 < to < 22 g/day and 22 to < 39 g/day were negatively associated with developing type 2 diabetes compared to complete alcohol abstainers. Alcohol consumption at levels of 39 to < 66 g/day and at levels of ≥ 66 g/day were positively associated with developing type 2 diabetes in participants with BMI < 25 kg/m2. All levels of alcohol consumption were negatively associated with developing type 2 diabetes in participants with BMI ≥ 25 kg/m2. Moderate-to-heavy alcohol consumption were positively associated with developing type 2 diabetes for participants with BMI < 25 kg/m2, whereas alcohol intake was negatively associated with developing type 2 diabetes among participants with BMI ≥ 25 kg/m2.
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Affiliation(s)
- Fuyuko Takahashi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Hiroshi Okada
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan
- Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, 5-55 Sotojima-Cho, Moriguchi, 570-8540, Japan
| | - Kazushiro Kurogi
- Department of Health Care Center, Panasonic Health Insurance Organization, 5-55 Sotojima-Cho, Moriguchi, 570-8540, Japan
| | - Hiroaki Murata
- Department of Orthopaedic Surgery, Matsushita Memorial Hospital, 5-55 Sotojima-Cho, Moriguchi, 570-8540, Japan
| | - Masato Ito
- Department of Health Care Center, Panasonic Health Insurance Organization, 5-55 Sotojima-Cho, Moriguchi, 570-8540, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan
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Lone AH, Tang J, Pignalosa A, Hsu HH, Abdul-Sater AA, Sweeney G. A novel blood-based bioassay to monitor adiponectin signaling. Int Immunopharmacol 2024; 132:111890. [PMID: 38547772 DOI: 10.1016/j.intimp.2024.111890] [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: 12/02/2023] [Revised: 03/07/2024] [Accepted: 03/14/2024] [Indexed: 05/01/2024]
Abstract
The diverse beneficial effects of adiponectin-receptor signaling, including its impact on the regulation of inflammatory processes in vivo, have resulted in development of adiponectin receptor agonists as a treatment for metabolic disorders. However, there are no established non-invasive bioassays for detection of adiponectin target engagement in humans or animal models. Here, we designed an assay using small amounts of blood to assess adiponectin action. Specifically, we tested effects of the small 10-amino acid peptide adiponectin receptor agonist, ALY688, in a sublethal LPS endotoxemia model in mice. LPS-induced pro-inflammatory cytokine levels in serum were significantly reduced in mice treated with ALY688, assessed via multiplex ELISA in flow cytometry. Furthermore, ALY688 alone significantly induced TGF-β release in serum 1 h after treatment and was elevated for up to 24 h. Additionally, using a flow-cytometry panel for detection of changes in circulating immune cell phenotypes, we observed a significant increase in absolute T cell counts in mice after ALY688 treatment. To assess changes in intracellular signaling effectors downstream of adiponectin, phospho-flow cytometry was conducted. There was a significant increase in phosphorylation of AMPK and p38-MAPK in mice after ALY688 treatment. We then used human donor immune cells (PBMCs) treated with ALY688 ex vivo and observed elevation of AMPK and p38-MAPK phosphorylation from baseline in response to ALY688. Together, these results indicate we can detect adiponectin action on immune cells in vivo by assessing adiponectin signaling pathway for AMPK and p38-MAPK, as well as pro-inflammatory cytokine levels. This new approach provides a blood-based bioassay for screening adiponectin action.
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Affiliation(s)
| | - Jialing Tang
- Department of Biology, York University, Toronto, ON, Canada
| | | | - Henry H Hsu
- Allysta Pharmaceuticals Inc., Bellevue, WA, USA
| | - Ali A Abdul-Sater
- School of Kinesiology and Health Science, York University, Toronto, ON, Canada.
| | - Gary Sweeney
- Department of Biology, York University, Toronto, ON, Canada.
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Mohammedsaeed W, Ahmed A, Alharbi N, Aljohani A, Alruwaithi R, Alharbi R, Alahmadi S. Evaluation of Adiponectin and ANGPTL8 in Women With Metabolic Syndrome in the Madinah Region of Saudi Arabia. Cureus 2023; 15:e44219. [PMID: 37767256 PMCID: PMC10522362 DOI: 10.7759/cureus.44219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2023] [Indexed: 09/29/2023] Open
Abstract
OBJECTIVE "Metabolic syndrome" (MetS) is a set of abnormalities that may be risk factors for cardiovascular disease (CVD) and diabetes. The current study sought to (1) determine MetS prevalence and (2) examine Adiponectin and ANGPTL8 levels in connection to MetS components and CVDs and diabetes risk in females with MetS. METHODS A total of 350, 20-35-year-old Saudi females were studied. Waist circumference (WC), body mass index (BMI), glucose, HbA1c, insulin, lipid profiles, and blood pressure (BP) were examined for MetS. ANGPTL8 and Adiponectin were also measured. RESULTS The patients were classified into two groups, namely MetS and non-MetS, according to the criteria established by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). We examined biomarker and anthropometric results between these groups. One hundred forty-four of 350 female participants (41.2%) had MetS, with a mean age of 30.5 years. Fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), ANGPTL8, adiponectin, and insulin resistance (IR) were statistically significant differences observed between the two groups. BP, BMI, WC, and Atherogenic Index of Plasma (AIP) all changed significantly (P ≤0.05). Correlation studies linked MetS components to higher ANGPTL-8 and reduced adiponectin. The levels of ANGPTL8 were shown to be influenced by the increase in FBG, TG, BP, IR, and AIP (P < 0.05). Factors such as FBG, BMI, WC, and IR have been found to have an inverse relationship with adiponectin levels. CONCLUSION 41.2% out of 350 Saudi females at Taibah University in the Madinah region had MetS, medium CVD risk, and slightly elevated BMI, TG, WC, and BP. To lower their risk of CVD and diabetes later in life, overweight young women should be evaluated for MetS. FBG and TG were substantially associated with ANGPTL8 while reducing adiponectin was associated with elevated TG and BP. Our findings may lead to ANGPTL8 and adiponectin's possible predictive function for CVD in early MetS in females.
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Affiliation(s)
- Walaa Mohammedsaeed
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Ahmed Ahmed
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Nada Alharbi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Amjaad Aljohani
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Razan Alruwaithi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Reem Alharbi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Shatha Alahmadi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
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Raghupathy R, McLean RR, Kiel DP, Hannan MT, Sahni S. Higher abdominal adiposity is associated with higher lean muscle mass but lower muscle quality in middle-aged and older men and women: the Framingham Heart Study. Aging Clin Exp Res 2023; 35:1477-1485. [PMID: 37166563 PMCID: PMC10450777 DOI: 10.1007/s40520-023-02427-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 04/26/2023] [Indexed: 05/12/2023]
Abstract
BACKGROUND The objective was to determine if abdominal fat is related to poor muscle health. METHODS This cross-sectional study included 428 males and 534 females with appendicular lean mass (ALM, kg) from dual-energy X-ray absorptiometry (DXA), grip strength (kg), and upper extremity muscle "quality" (grip strength/arm lean mass) measured (1996-2001) in the Framingham Offspring Study. Sex-specific linear regressions associated adiposity measures [waist circumference (WC, cm) and visceral adipose tissue (VAT, cm3), and subcutaneous adipose tissue (SAT, cm3)] as Z-scores with each measure of muscle, adjusting for covariates. Models were further stratified by body mass index (BMI, < 30, ≥ 30 kg/m2). RESULTS Mean (± SD) age was 60 ± 9 years and BMI was 28.9 ± 4.6 kg/m2 (men) and 27.7 ± 5.8 kg/m2, (women). In men, the BMI-stratified analyses showed higher WC was associated with higher ALM (P < 0.0001 each) but with lower muscle quality (P < 0.02) in both BMI groups. Higher SAT was also associated with higher ALM (P = 0.0002) and lower muscle quality (P = 0.0002) in men with BMI < 30, but not in obese men. In women, higher WC, SAT, and VAT were each associated with higher ALM but lower muscle quality, particularly in obese women. Higher SAT (P = 0.05) and VAT (P = 0.04) were associated with higher quadriceps strength in women with BMI < 30 kg/m2 but not in obese women. CONCLUSIONS Higher abdominal fat may be associated with greater lean mass but poorer muscle quality, particularly in obese women. This suggests that adipose tissue may have endocrine influences on muscle, which should be confirmed in longitudinal studies.
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Affiliation(s)
- Rachana Raghupathy
- Washington University School of Medicine in St. Louis, St. Louis, MO, USA
- Northeast Ohio Medical University, Rootstown, OH, USA
| | - Robert R McLean
- CorEvitas, LLC, Boston, MA, USA
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, MA, USA
| | - Douglas P Kiel
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, MA, USA
| | - Marian T Hannan
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, MA, USA
| | - Shivani Sahni
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, MA, USA.
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Martínez-Fernández L, Burgos M, Sáinz N, Laiglesia LM, Arbones-Mainar JM, González-Muniesa P, Moreno-Aliaga MJ. Maresin 1 Exerts a Tissue-Specific Regulation of Adipo-Hepato-Myokines in Diet-Induced Obese Mice and Modulates Adipokine Expression in Cultured Human Adipocytes in Basal and Inflammatory Conditions. Biomolecules 2023; 13:919. [PMID: 37371501 DOI: 10.3390/biom13060919] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
This study analyses the effects of Maresin 1 (MaR1), a docosahexaenoic acid (DHA)-derived specialized proresolving lipid mediator with anti-inflammatory and insulin-sensitizing actions, on the expression of adipokines, including adiponectin, leptin, dipeptidyl peptidase 4 (DPP-4), cardiotrophin-1 (CT-1), and irisin (FNDC5), both in vitro and in in vivo models of obesity. The in vivo effects of MaR1 (50 μg/kg, 10 days, oral gavage) were evaluated in epididymal adipose tissue (eWAT), liver and muscle of diet-induced obese (DIO) mice. Moreover, two models of human differentiated primary adipocytes were incubated with MaR1 (1 and 10 nM, 24 h) or with a combination of tumor necrosis factor-α (TNF-α, 100 ng/mL) and MaR1 (1-200 nM, 24 h) and the expression and secretion of adipokines were measured in both models. MaR1-treated DIO mice exhibited an increased expression of adiponectin and Ct-1 in eWAT, increased expression of Fndc5 and Ct-1 in muscle and a decreased expression of hepatic Dpp-4. In human differentiated adipocytes, MaR1 increased the expression of ADIPONECTIN, LEPTIN, DPP4, CT-1 and FNDC5. Moreover, MaR1 counteracted the downregulation of ADIPONECTIN and the upregulation of DPP-4 and LEPTIN observed in adipocytes treated with TNF-α. Differential effects for TNF-α and MaR1 on the expression of CT-1 and FNDC5 were observed between both models of human adipocytes. In conclusion, MaR1 reverses the expression of specific adipomyokines and hepatokines altered in obese mice in a tissue-dependent manner. Moreover, MaR1 regulates the basal expression of adipokines in human adipocytes and counteracts the alterations of adipokines expression induced by TNF-α in vitro. These actions could contribute to the metabolic benefits of this lipid mediator.
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Affiliation(s)
- Leyre Martínez-Fernández
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
| | - Miguel Burgos
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
- IDISNA-Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Neira Sáinz
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
| | - Laura M Laiglesia
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
| | - José Miguel Arbones-Mainar
- Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Instituto de Investigación Sanitaria (IIS) Aragón, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Pedro González-Muniesa
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
- IDISNA-Navarra Institute for Health Research, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - María J Moreno-Aliaga
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
- IDISNA-Navarra Institute for Health Research, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
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Lee SH, Shin C, Ko YH, Lee MS, Park MH, Pae CU, Yoon HK, Han C. Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2023; 21:147-161. [PMID: 36700321 PMCID: PMC9889913 DOI: 10.9758/cpn.2023.21.1.147] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 01/27/2023]
Abstract
Objective Although several previous studies have examined the association between late-life depression and blood adipokine levels, a marker of chronic inflammation, no studies have comprehensively considered the effects of metabolic syndrome, which is known to affect blood adipokine levels. This study examined blood adipokine levels in geriatric depression after adjusting for the effects of metabolic syndrome. Methods Participants were selected from the Ansan Geriatric Study (depression group [n = 76] and control group [n = 76]). Blood concentrations of four adipokines (adiponectin, resistin, neutrophil-gelatinase-associated lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) were measured using immunoassays. The effects of blood adipokine concentration on the diagnosis of depression were analyzed using multivariate logistic regression to adjust for the effects of metabolic syndrome and potential confounding factors. Results When the effects of metabolic syndrome and potential confounding factors were adjusted, only PAI-1 could explain the diagnosis of depression among all the adipokines. The depression group showed a lower blood PAI-1 level than the control group. Adiponectin, resistin, and NGAL could not explain the diagnosis of depression when the effects of metabolic syndrome and potential confounding factors were adjusted. Conclusion This study suggests the possibility that the blood PAI-1 levels in clinically pathological late-life depression may show contrasting results to those with subclinical depressive symptoms. Additionally, considering that most previous studies have been conducted with pre-geriatric populations, the study suggests the possibility that geriatric depression may show inflammatory changes with patterns that are different from those of depression in the pre-geriatric population.
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Affiliation(s)
- Seung-Hoon Lee
- Department of Psychiatry, Veterans Health Service Medical Center, Seoul, Korea
| | - Cheolmin Shin
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Young-Hoon Ko
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Moon-Soo Lee
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Moon Ho Park
- Department of Neurology, Korea University College of Medicine, Seoul, Korea
| | - Chi-Un Pae
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ho-Kyoung Yoon
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Changsu Han
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea,Address for correspondence: Changsu Han Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea, E-mail: , ORCID: https://orcid.org/0000-0002-4021-8907
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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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10
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Kamalumpundi V, Shams E, Tucker C, Cheng L, Peterson J, Thangavel S, Ofori O, Correia M. Mechanisms and pharmacotherapy of hypertension associated with type 2 diabetes. Biochem Pharmacol 2022; 206:115304. [DOI: 10.1016/j.bcp.2022.115304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 10/09/2022] [Accepted: 10/11/2022] [Indexed: 11/28/2022]
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11
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Reiterer M, Gilani A, Lo JC. Pancreatic Islets as a Target of Adipokines. Compr Physiol 2022; 12:4039-4065. [PMID: 35950650 DOI: 10.1002/cphy.c210044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Rising rates of obesity are intricately tied to the type 2 diabetes epidemic. The adipose tissues can play a central role in protection against or triggering metabolic diseases through the secretion of adipokines. Many adipokines may improve peripheral insulin sensitivity through a variety of mechanisms, thereby indirectly reducing the strain on beta cells and thus improving their viability and functionality. Such effects will not be the focus of this article. Rather, we will focus on adipocyte-secreted molecules that have a direct effect on pancreatic islets. By their nature, adipokines represent potential druggable targets that can reach the islets and improve beta-cell function or preserve beta cells in the face of metabolic stress. © 2022 American Physiological Society. Compr Physiol 12:1-27, 2022.
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Affiliation(s)
- Moritz Reiterer
- Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA
| | - Ankit Gilani
- Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA
| | - James C Lo
- Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA
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12
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Luo L, Liu M. Adiponectin: friend or foe in obesity and inflammation. MEDICAL REVIEW (2021) 2022; 2:349-362. [PMID: 37724325 PMCID: PMC10388816 DOI: 10.1515/mr-2022-0002] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/27/2022] [Indexed: 09/20/2023]
Abstract
Adiponectin is an adipokine predominantly produced by fat cells, circulates and exerts insulin-sensitizing, cardioprotective and anti-inflammatory effects. Dysregulation of adiponectin and/or adiponectin signaling is implicated in a number of metabolic diseases such as obesity, insulin resistance, diabetes, and cardiovascular diseases. However, while the insulin-sensitizing and cardioprotective effects of adiponectin have been widely appreciated in the field, the obesogenic and anti-inflammatory effects of adiponectin are still of much debate. Understanding the physiological function of adiponectin is critical for adiponectin-based therapeutics for the treatment of metabolic diseases.
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Affiliation(s)
- Liping Luo
- Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Meilian Liu
- Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
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13
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Essential Amino Acids-Rich Diet Decreased Adipose Tissue Storage in Adult Mice: A Preliminary Histopathological Study. Nutrients 2022; 14:nu14142915. [PMID: 35889872 PMCID: PMC9316883 DOI: 10.3390/nu14142915] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/11/2022] [Accepted: 07/13/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Excess body adipose tissue accumulation is a common and growing health problem caused by an unbalanced diet and/or junk food. Although the effects of dietary fat and glucose on lipid metabolism regulation are well known, those of essential amino acids (EAAs) have been poorly investigated. Our aim was to study the influence of a special diet containing all EAAs on retroperitoneal white adipose tissue (rpWAT) and interscapular brown adipose tissue (BAT) of mice. Methods: Two groups of male Balb/C mice were used. The first was fed with a standard diet. The second was fed with an EAAs-rich diet (EAARD). After 3 weeks, rpWAT and BAT were removed and prepared for subsequent immunohistochemical analysis. Results: EAARD, although consumed significantly less, moderately reduced body weight and BAT, but caused a massive reduction in rpWAT. Conversely, the triceps muscle increased in mass. In rpWAT, the size of adipocytes was very small, with increases in leptin, adiponectin and IL-6 immunostaining. In BAT, there was a reduction in lipid droplet size and a simultaneous increase in UCP-1 and SIRT-3. Conclusions: A diet containing a balanced mixture of free EAA may modulate body adiposity in mice, promoting increased thermogenesis.
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14
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Poman DS, Motwani L, Asif N, Patel A, Vedantam D. Pancreatic Cancer and the Obesity Epidemic: A Narrative Review. Cureus 2022; 14:e26654. [PMID: 35959181 PMCID: PMC9360631 DOI: 10.7759/cureus.26654] [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] [Accepted: 07/07/2022] [Indexed: 11/05/2022] Open
Abstract
Pancreatic cancer (PC) is one of the most frequent causes of death. It usually affects older individuals with incidence closely approaching mortality due to its early asymptomatic feature and highly metastatic nature. Multiple risk factors such as family history, smoking, and germline mutations are associated with PC development, with obesity being one of the controllable factors. This review article focuses on the compilation of various studies to help establish a correlation between obesity or an increased body mass index and PC development. Hence, in this review, we have summarised multiple biological mechanisms of PC development induced by obesity, including insulin resistance, inflammation, beta-cell dysfunction, and oxidative stress, to prove that their correlation when combined with other factors, such as smoking, alcohol and chronic pancreatitis, may increase its risk. We have also reviewed potential diagnostic and screening techniques, such as evaluating precancerous lesions in high-risk patients and management plans discussing upcoming advances in treatment tactics such as neoadjuvant therapy, to reduce post-operative complications.
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Affiliation(s)
| | - Lakshya Motwani
- Research and Development, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Nailah Asif
- Research, Ras Al Khaimah (RAK) College of Medical Sciences, Ras Al Khaimah, ARE
| | - Apurva Patel
- Research, Gujarat Medical Education & Research Society (GMERS) Medical College, Gotri, Vadodara, IND
| | - Deepanjali Vedantam
- Internal Medicine, Kamineni Academy of Medical Sciences and Research Center, Hyderabad, IND
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15
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Sabaratnam R, Skov V, Paulsen SK, Juhl S, Kruse R, Hansen T, Halkier C, Kristensen JM, Vind BF, Richelsen B, Knudsen S, Dahlgaard J, Beck-Nielsen H, Kruse TA, Højlund K. A Signature of Exaggerated Adipose Tissue Dysfunction in Type 2 Diabetes Is Linked to Low Plasma Adiponectin and Increased Transcriptional Activation of Proteasomal Degradation in Muscle. Cells 2022; 11:cells11132005. [PMID: 35805088 PMCID: PMC9265693 DOI: 10.3390/cells11132005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 06/12/2022] [Accepted: 06/21/2022] [Indexed: 01/27/2023] Open
Abstract
Insulin resistance in skeletal muscle in type 2 diabetes (T2D) is characterized by more pronounced metabolic and molecular defects than in obesity per se. There is increasing evidence that adipose tissue dysfunction contributes to obesity-induced insulin resistance in skeletal muscle. Here, we used an unbiased approach to examine if adipose tissue dysfunction is exaggerated in T2D and linked to diabetes-related mechanisms of insulin resistance in skeletal muscle. Transcriptional profiling and biological pathways analysis were performed in subcutaneous adipose tissue (SAT) and skeletal muscle biopsies from 17 patients with T2D and 19 glucose-tolerant, age and weight-matched obese controls. Findings were validated by qRT-PCR and western blotting of selected genes and proteins. Patients with T2D were more insulin resistant and had lower plasma adiponectin than obese controls. Transcriptional profiling showed downregulation of genes involved in mitochondrial oxidative phosphorylation and the tricarboxylic-acid cycle and increased expression of extracellular matrix (ECM) genes in SAT in T2D, whereas genes involved in proteasomal degradation were upregulated in the skeletal muscle in T2D. qRT-PCR confirmed most of these findings and showed lower expression of adiponectin in SAT and higher expression of myostatin in muscle in T2D. Interestingly, muscle expression of proteasomal genes correlated positively with SAT expression of ECM genes but inversely with the expression of ADIPOQ in SAT and plasma adiponectin. Protein content of proteasomal subunits and major ubiquitin ligases were unaltered in the skeletal muscle of patients with T2D. A transcriptional signature of exaggerated adipose tissue dysfunction in T2D, compared with obesity alone, is linked to low plasma adiponectin and increased transcriptional activation of proteasomal degradation in skeletal muscle.
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Affiliation(s)
- Rugivan Sabaratnam
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
- Department of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark; (T.H.); (C.H.)
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
| | - Vibe Skov
- Department of Hematology, Zealand University Hospital, DK-4000 Roskilde, Denmark;
| | - Søren K. Paulsen
- Department of Pathology, Viborg Regional Hospital, DK-8800 Viborg, Denmark;
| | - Stine Juhl
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
- Department of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark; (T.H.); (C.H.)
| | - Rikke Kruse
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
- Department of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark; (T.H.); (C.H.)
| | - Thea Hansen
- Department of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark; (T.H.); (C.H.)
| | - Cecilie Halkier
- Department of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark; (T.H.); (C.H.)
| | - Jonas M. Kristensen
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, University of Copenhagen, DK-2100 Copenhagen, Denmark
| | - Birgitte F. Vind
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
| | - Bjørn Richelsen
- Steno Diabetes Center Aarhus, Aarhus University Hospital, DK-8200 Aarhus N, Denmark;
| | - Steen Knudsen
- Allarity Therapeutics Europe, DK-2970 Hørsholm, Denmark;
| | - Jesper Dahlgaard
- Program for Mind and Body in Mental Health, Research Centre for Health and Welfare Technology, VIA University College, DK-8200 Aarhus, Denmark;
- Department of Clinical Medicine, Aarhus University, DK-8200 Aarhus, Denmark
| | - Henning Beck-Nielsen
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
| | - Torben A. Kruse
- Department of Clinical Genetics, Odense University Hospital, DK-5000 Odense C, Denmark;
| | - Kurt Højlund
- Steno Diabetes Center Odense, Odense University Hospital, DK-5000 Odense C, Denmark; (R.S.); (S.J.); (R.K.); (J.M.K.); (B.F.V.); (H.B.-N.)
- Department of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark; (T.H.); (C.H.)
- Correspondence: ; Tel.: +45-2532-0648
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16
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Qian Y, Xia F, Zuo Y, Zhong M, Yang L, Jiang Y, Zou C. Do patients with Prader-Willi syndrome have favorable glucose metabolism? Orphanet J Rare Dis 2022; 17:187. [PMID: 35525976 PMCID: PMC9077846 DOI: 10.1186/s13023-022-02344-3] [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: 01/08/2022] [Accepted: 04/26/2022] [Indexed: 11/26/2022] Open
Abstract
Background In recent years, more studies have observed that patients with Prader–Willi syndrome have lower insulin levels and lower insulin resistance than body mass index-matched controls, which may suggest protected glucose metabolism. Method The PubMed and Web of Science online databases were searched to identify relevant studies published in the English language using the terms “Prader–Willi syndrome” with “glucose”, “insulin”, “diabetes mellitus”, “fat”, “adipo*”, “ghrelin”, “oxytocin”, “irisin” or “autonomic nervous system”. Results The prevalence of impaired glucose intolerance, type 2 diabetes mellitus and some other obesity-associated complications in patients with Prader–Willi syndrome tends to be lower when compared to that in general obesity, which is consistent with the hypothetically protected glucose metabolism. Factors including adipose tissue, adiponectin, ghrelin, oxytocin, irisin, growth hormone and the autonomic nervous system possibly modulate insulin sensitivity in patients with Prader–Willi syndrome. Conclusion Although lower insulin levels, lower IR and protected glucose metabolism are widely reported in PWS patients, the causes are still mysterious. Based on existing knowledge, we cannot determine which factor is of utmost importance and what are the underlying mechanisms, and further research is in urgent need.
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Affiliation(s)
- Yanjie Qian
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Fangling Xia
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Yiming Zuo
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Mianling Zhong
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Lili Yang
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Yonghui Jiang
- Department of Genetics, Yale University School of Medicine, New Haven, USA
| | - Chaochun Zou
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China.
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Effect of Parathyroidectomy on Metabolic Homeostasis in Primary Hyperparathyroidism. J Clin Med 2022; 11:jcm11051373. [PMID: 35268464 PMCID: PMC8911089 DOI: 10.3390/jcm11051373] [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: 01/13/2022] [Revised: 02/20/2022] [Accepted: 02/28/2022] [Indexed: 12/10/2022] Open
Abstract
Background: The benefits of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism (PHPT) are controversial. This monocentric, observational, prospective study aimed to assess the effects of parathyroidectomy on glucose and lipid metabolism in classic or mild PHPT. Methods: Patients who underwent parathyroidectomy for classic (calcemia >2.85 mmol/L) or mild PHPT (calcemia ≤2.85 mmol/L) between 2016 and 2019 were included. A metabolic assessment was performed before and 1 year after parathyroidectomy. Patients with a history of diabetes were excluded. Results: Nineteen patients had classic and 120 had mild PHPT. Ninety-five percent were normocalcemic 6 months after surgery. Fasting plasma glucose and insulin levels decreased after parathyroidectomy in patients with mild PHPT (p < 0.001). HOMA-IR decreased after surgery in the overall population (p < 0.001), while plasma adiponectin concentrations increased in patients with both classic (p = 0.005) and mild PHPT (p < 0.001). Plasma triglyceride levels decreased significantly only in patients with classic PHPT (p = 0.021). Plasma PCSK9 levels decreased in patients with mild PHPT (p < 0.001). Conclusions: Parathyroidectomy for PHPT improves insulin resistance and decreases plasma triglyceride levels in classic PHPT and plasma PCSK9 levels in mild PHPT. Further studies are needed to better characterize the consequences of such metabolic risk factors’ improvements on cardiovascular events.
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18
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Giudici KV, de França NAG, Peters BSE, Fisberg RM, Martini LA. Associations between markers of glucose metabolism and bone measures among diabetic and non-diabetic adults. J Diabetes Metab Disord 2021; 20:1247-1255. [PMID: 34900776 DOI: 10.1007/s40200-021-00849-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 07/03/2021] [Indexed: 11/18/2022]
Abstract
Purpose To investigate the relationships between bone measures, vitamin D status and markers of glucose metabolism among diabetic and non-diabetic adults. Methods Cross sectional study with 298 adults (mean age 57.5 years, SD = 14.8; 44.3% male, 16.9% diabetic) participants of the Health Survey-São Paulo (ISA-Capital) 2014-2015. Blood samples were collected to assess serum glucose, insulin and 25 hydroxyvitamin D [25(OH)D] concentrations. Dual-energy x-ray absorptiometry (DXA) was performed to determine total body fat; total lean mass; full body bone mineral density (BMD); lumbar spine BMD and bone mineral content (BMC); and femur BMD and BMC. Fat mass index (FMI), lean mass index (LMI), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and of β-pancreatic cell function (HOMA-β) were calculated. Linear regression analysis were performed. Results Multiple bone measures were associated with markers of glucose metabolism in analyses adjusted by age and sex. However, after additional adjustments by LMI, FMI and serum 25(OH)D, only associations of lumbar spine BMC with HOMA-IR (β = 0.167; p = 0.035) and QUICKI (β = -1.879; p = 0.027) persisted, in the subgroup of diabetic participants. Analysis restricted to diabetic subjects revealed stronger correlations between bone parameters and markers of glucose metabolism. Conclusions Our study observed positive associations between BMD and markers of insulin resistance among a sample of adults. Correlations were stronger among diabetic subjects, and some associations between bone and glucose metabolism were independent of adiposity. Findings reinforce the need of further research for better understanding the bidirectional and multifactorial crosstalk between glucose homeostasis and bone metabolism.
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Affiliation(s)
- Kelly Virecoulon Giudici
- Nutrition Department, School of Public Health, University of São Paulo, Avenida Doutor Arnaldo, 715, Cerqueira César, São Paulo, SP Zip Code 01246-904 Brazil.,Present Address: Institute of Aging (Gerontopole), Toulouse University Hospital (CHU), Université Toulouse III Paul Sabatier, Toulouse, France
| | - Natasha Aparecida Grande de França
- Nutrition Department, School of Public Health, University of São Paulo, Avenida Doutor Arnaldo, 715, Cerqueira César, São Paulo, SP Zip Code 01246-904 Brazil
| | - Bárbara Santarosa Emo Peters
- Nutrition Department, School of Public Health, University of São Paulo, Avenida Doutor Arnaldo, 715, Cerqueira César, São Paulo, SP Zip Code 01246-904 Brazil
| | - Regina Mara Fisberg
- Nutrition Department, School of Public Health, University of São Paulo, Avenida Doutor Arnaldo, 715, Cerqueira César, São Paulo, SP Zip Code 01246-904 Brazil
| | - Lígia Araújo Martini
- Nutrition Department, School of Public Health, University of São Paulo, Avenida Doutor Arnaldo, 715, Cerqueira César, São Paulo, SP Zip Code 01246-904 Brazil
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Abstract
Obesity is a major risk factor for the development of comorbidities such as type 2 diabetes, neurodegenerative disorders, osteoarthritis, cancer, cardiovascular and renal diseases. The onset of obesity is linked to an increase of senescent cells within adipose tissue and other organs. Cellular senescence is a stress response that has been shown to be causally linked to aging and development of various age-related diseases such as obesity. The senescence-associated-secretory phenotype of senescent cells creates a chronic inflammatory milieu that leads to local and systemic dysfunction. The elimination of senescent cells using pharmacological approaches (i.e., senolytics) has been shown to delay, prevent, or alleviate obesity-related organ dysfunction.
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Affiliation(s)
- Selim Chaib
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
| | - Tamara Tchkonia
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
| | - James L Kirkland
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
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20
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Strzałkowska B, Dawidowicz M, Ochman B, Świętochowska E. The role of adipokines in leiomyomas development. Exp Mol Pathol 2021; 123:104693. [PMID: 34637783 DOI: 10.1016/j.yexmp.2021.104693] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 09/06/2021] [Accepted: 09/28/2021] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Many women of premenopausal age suffer from uterine leiomyomas, which are benign tumors of the uterus. Despite the high prevalence of uterine leiomyomas underlying pathogenesis mechanisms are not fully elucidated. Early data showed a positive correlation between increased levels of adipose tissue and leiomyomas prevalence. Adipose tissue cells-adipocytes can play a potential role in leiomyomas formation by producing and secreting adipokines. AIM The aim of this study is to summarize the current knowledge on the potential relation between adipokines and leiomyomas basing on current data analyze, and justify future research directions. METHODOLOGY This review is based on pertinent articles searched using PubMed, encompassing all available literature. The key search words were as follows: adipokines, leiomyoma, TNFα, leptin, adiponectin, visfatin, resistin, omentin, lipocalin, apelin, adipsin, chemerin. Time was not an exclusion criterium due to few available studies on this subject. SUMMARY The results of the studies are inconclusive, but the vast majority indicates a significant connection between the adipokines and the leiomyomas. According to the majority of studies, TNFα contributes to the development of leiomyomas by inhibiting apoptosis, increasing migration of leiomyomas, and increasing fibrosis of leiomyomas. Most of the studies on the effects of leptin also indicate the relation between leptin and leiomyomas development. In the case of adiponectin released from mast cells' granularity, it is possible that adiponectin increases angiogenesis in leiomyomas. Under physiological conditions, adiponectin has the potential to inhibit the development of leiomyomas. The authors suggested that adiponectin affects leiomyomas via an insulin-dependent pathway or via an estrogen-dependent pathway. Most probably leptin contributes to the formation of myomas and adiponectin prevents this. More research is needed to understand better the influence of these molecules on the pathogenesis of leiomyomas.
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Affiliation(s)
- Bogumiła Strzałkowska
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland.
| | - Miriam Dawidowicz
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Błażej Ochman
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Elżbieta Świętochowska
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland
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21
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Frey S, Mirallié É, Cariou B, Blanchard C. Impact of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism: A narrative review. Nutr Metab Cardiovasc Dis 2021; 31:981-996. [PMID: 33612382 DOI: 10.1016/j.numecd.2020.12.029] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 11/23/2020] [Accepted: 12/27/2020] [Indexed: 12/22/2022]
Abstract
AIMS Primary hyperparathyroidism (PHPT), one of the most frequent endocrine disorders, is not only associated with bone and kidney disorders but also with increased cardiovascular risk. This cardiovascular risk is not part of the indication for surgery owing to discordant evidence of the effects of parathyroidectomy (PTX), especially in mild PHPT which is the most common presentation of PHPT. This literature review focuses on the effects of PTX on the cardiovascular risk in PHPT. The MEDLINE database was searched via the PubMed interface, selecting relevant articles published after 1990 in English. DATA SYNTHESIS In the most recent series, PTX appeared to have a positive impact on cardiovascular morbidity and mortality. Surgery improves arterial hypertension, markers of glucose homeostasis, vascular and cardiac remodeling and electrocardiographic impairments due to classical PHPT. However, the results of surgery on mild PHPT are conflicting. CONCLUSIONS PTX seems to improve cardiovascular risk in patients presenting the classical form of PHPT. This improvement is correlated with preoperative serum calcium and/or PTH level, depending on the cardiovascular risk factor. However, many aspects of this improvement are not fully understood. Future studies should assess the effects of PTX on nocturnal hypertension, cardiac morphology and functions. The results for mild PHPT are conflicting owing to the limited size of the cohorts included in studies and the lack of randomized trials. Surgery is not currently recommended for patients presenting mild PHPT based on the cardiovascular risk and more studies are needed to better understand the interest of PTX on cardiovascular outcomes.
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Affiliation(s)
- Samuel Frey
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l'Appareil Digestif, CHU de Nantes, Nantes, France; Université de Nantes, Quai de Tourville, 44000, Nantes, France
| | - Éric Mirallié
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l'Appareil Digestif, CHU de Nantes, Nantes, France; Université de Nantes, Quai de Tourville, 44000, Nantes, France
| | - Bertrand Cariou
- Université de Nantes, Quai de Tourville, 44000, Nantes, France; L'institut du Thorax, UNIV NANTES, CNRS, INSERM, CHU de Nantes, Nantes, France; Service d'Endocrinologie et Maladies Métaboliques, l'Institut du Thorax, CHU de Nantes, Nantes, France.
| | - Claire Blanchard
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l'Appareil Digestif, CHU de Nantes, Nantes, France; Université de Nantes, Quai de Tourville, 44000, Nantes, France; L'institut du Thorax, UNIV NANTES, CNRS, INSERM, CHU de Nantes, Nantes, France.
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He Q, Bo J, Shen R, Li Y, Zhang Y, Zhang J, Yang J, Liu Y. S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes. J Diabetes Res 2021; 2021:1341750. [PMID: 34751249 PMCID: PMC8571914 DOI: 10.1155/2021/1341750] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 12/24/2020] [Accepted: 01/04/2021] [Indexed: 02/06/2023] Open
Abstract
The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the "Ominous Octet" theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting β cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.
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Affiliation(s)
- Qiong He
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Jiaqi Bo
- Department of Second Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ruihua Shen
- Department of Second Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Yan Li
- Department of Second Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Yi Zhang
- Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Jiaxin Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Jing Yang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Yunfeng Liu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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The Influence of Physical Activity on the Bioactive Lipids Metabolism in Obesity-Induced Muscle Insulin Resistance. Biomolecules 2020; 10:biom10121665. [PMID: 33322719 PMCID: PMC7764345 DOI: 10.3390/biom10121665] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 12/14/2022] Open
Abstract
High-fat diet consumption and lack of physical activity are important risk factors for metabolic disorders such as insulin resistance and cardiovascular diseases. Insulin resistance is a state of a weakened response of tissues such as skeletal muscle, adipose tissue, and liver to insulin, which causes an increase in blood glucose levels. This condition is the result of inhibition of the intracellular insulin signaling pathway. Skeletal muscle is an important insulin-sensitive tissue that accounts for about 80% of insulin-dependent glucose uptake. Although the exact mechanism by which insulin resistance is induced has not been thoroughly understood, it is known that insulin resistance is most commonly associated with obesity. Therefore, it is believed that lipids may play an important role in inducing insulin resistance. Among lipids, researchers’ attention is mainly focused on biologically active lipids: diacylglycerols (DAG) and ceramides. These lipids are able to regulate the activity of intracellular enzymes, including those involved in insulin signaling. Available data indicate that physical activity affects lipid metabolism and has a positive effect on insulin sensitivity in skeletal muscles. In this review, we have presented the current state of knowledge about the impact of physical activity on insulin resistance and metabolism of biologically active lipids.
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Santiprabhob J, Chokephaibulkit K, Khantee P, Maleesatharn A, Phonrat B, Phongsamart W, Lapphra K, Wittawatmongkol O, Rungmaitree S, Tanchaweng S, Maturapat S, Lermankul W, Tungtrongchitr R. Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors. Cytokine 2020; 136:155145. [PMID: 32920318 DOI: 10.1016/j.cyto.2020.155145] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/30/2020] [Accepted: 05/23/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (β = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (β = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.
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Affiliation(s)
- Jeerunda Santiprabhob
- Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Kulkanya Chokephaibulkit
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Puttichart Khantee
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Alan Maleesatharn
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Benjaluck Phonrat
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
| | - Wanatpreeya Phongsamart
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Keswadee Lapphra
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Orasri Wittawatmongkol
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Supattra Rungmaitree
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Surapong Tanchaweng
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Sirinoot Maturapat
- Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Watcharee Lermankul
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Rungsunn Tungtrongchitr
- Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Pretz D, Le Foll C, Rizwan MZ, Lutz TA, Tups A. Hyperleptinemia as a contributing factor for the impairment of glucose intolerance in obesity. FASEB J 2020; 35:e21216. [PMID: 33230896 DOI: 10.1096/fj.202001147r] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 10/20/2020] [Accepted: 11/10/2020] [Indexed: 12/21/2022]
Abstract
Obesity has emerged as a major risk factor for insulin resistance leading to the development of type 2 diabetes (T2D). The condition is characterized by high circulating levels of the adipose-derived hormone leptin and a state of chronic low-grade inflammation. Pro-inflammatory signaling in the hypothalamus is associated with a decrease of central leptin- and insulin action leading to impaired systemic glucose tolerance. Intriguingly, leptin not only regulates body weight and glucose homeostasis but also acts as a pro-inflammatory cytokine. Here we demonstrate that increasing leptin levels (62,5 µg/kg/d, PEGylated leptin) in mice fed a high-fat diet (HFD) exacerbated body weight gain and aggravated hypothalamic micro- as well as astrogliosis. In contrast, administration of a predetermined dose of a long-acting leptin antagonist (100 µg/kg/d, PESLAN) chosen to block excessive leptin signaling during diet-induced obesity (DIO) showed the opposite effect and significantly improved glucose tolerance as well as decreased the total number of microglia and astrocytes in the hypothalamus of mice fed HFD. These results suggest that high levels of leptin, such as in obesity, worsen HFD-induced micro-and astrogliosis, whereas the partial reduction of hyperleptinemia in DIO mice may have beneficial metabolic effects and improves hypothalamic gliosis.
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Affiliation(s)
- Dominik Pretz
- Centre for Neuroendocrinology, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.,Department of Animal Physiology, Faculty of Biology, Philipps-University Marburg, Marburg, Germany
| | - Christelle Le Foll
- Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland
| | - Mohammed Z Rizwan
- Centre for Neuroendocrinology, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand
| | - Thomas A Lutz
- Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland
| | - Alexander Tups
- Centre for Neuroendocrinology, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.,Department of Animal Physiology, Faculty of Biology, Philipps-University Marburg, Marburg, Germany
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Berezin AE, Berezin AA, Lichtenauer M. Emerging Role of Adipocyte Dysfunction in Inducing Heart Failure Among Obese Patients With Prediabetes and Known Diabetes Mellitus. Front Cardiovasc Med 2020; 7:583175. [PMID: 33240938 PMCID: PMC7667132 DOI: 10.3389/fcvm.2020.583175] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 10/05/2020] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue dysfunction is a predictor for cardiovascular (CV) events and heart failure (HF) in patient population with obesity, metabolic syndrome, and known type 2 diabetes mellitus. Previous preclinical and clinical studies have yielded controversial findings regarding the role of accumulation of adipose tissue various types in CV risk and HF-related clinical outcomes in obese patients. There is evidence for direct impact of infiltration of epicardial adipocytes into the underlying myocardium to induce adverse cardiac remodeling and mediate HF development and atrial fibrillation. Additionally, perivascular adipocytes accumulation is responsible for release of proinflammatory adipocytokines (adiponectin, leptin, resistin), stimulation of oxidative stress, macrophage phenotype switching, and worsening vascular reparation, which all lead to microvascular inflammation, endothelial dysfunction, atherosclerosis acceleration, and finally to increase in CV mortality. However, systemic effects of white and brown adipose tissue can be different, and adipogenesis including browning of adipose tissue and deficiency of anti-inflammatory adipocytokines (visfatin, omentin, zinc-α2-glycoprotein, glypican-4) was frequently associated with adipose triglyceride lipase augmentation, altered glucose homeostasis, resistance to insulin of skeletal muscles, increased cardiomyocyte apoptosis, lowered survival, and weak function of progenitor endothelial cells, which could significantly influence on HF development, as well as end-organ fibrosis and multiple comorbidities. The exact underlying mechanisms for these effects are not fully understood, while they are essential to help develop improved treatment strategies. The aim of the review is to summarize the evidence showing that adipocyte dysfunction may induce the onset of HF and support advance of HF through different biological mechanisms involving inflammation, pericardial, and perivascular adipose tissue accumulation, adverse and electrical cardiac remodeling, and skeletal muscle dysfunction. The unbalancing effects of natriuretic peptides, neprilysin, and components of renin-angiotensin system, as exacerbating cause of altered adipocytokine signaling on myocardium and vasculature, in obesity patients at high risk of HF are disputed. The profile of proinflammatory and anti-inflammatory adipocytokines as promising biomarker for HF risk stratification is discussed in the review.
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Affiliation(s)
- Alexander E. Berezin
- Internal Medicine Department, State Medical University, Ministry of Health of Ukraine, Zaporozhye, Ukraine
| | - Alexander A. Berezin
- Internal Medicine Department, Medical Academy of Post-Graduate Education, Ministry of Health of Ukraine, Zaporozhye, Ukraine
| | - Michael Lichtenauer
- Division of Cardiology, Department of Internal Medicine II, Paracelsus Medical University Salzburg, Salzburg, Austria
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Hosseinzadeh M, Razmpoosh E, Elham shareghfarid, Hosseinzadeh E, Hadinedoushan H, Salami MA, Khosravi M, Amini M, Mozaffari-Khosravi H. The effect of a single mega dose injection of vitamin D on serum adiponectin concentration at first gestational diabetes mellitus: A randomized controlled clinical trial. CLINICAL NUTRITION EXPERIMENTAL 2020. [DOI: 10.1016/j.yclnex.2020.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Francischetti EA, Dezonne RS, Pereira CM, de Moraes Martins CJ, Celoria BMJ, de Oliveira PAC, de Abreu VG. Insights Into the Controversial Aspects of Adiponectin in Cardiometabolic Disorders. Horm Metab Res 2020; 52:695-707. [PMID: 32927496 DOI: 10.1055/a-1239-4349] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have reported high circulating adiponectin levels positively associated with cardiovascular mortality and all-cause mortality. These results are biologically intriguing and counterintuitive, and came to be termed "the adiponectin paradox". Adiponectin paradox is frequently associated with adiponectin resistance, a concept related with the downregulation of adiponectin receptors in insulin-resistant states. We review this contradiction between the apparent role of adiponectin as a health promoter and the recent evidence from Mendelian randomization studies indicating that circulating adiponectin levels are an unexpected predictor of increased morbidity and mortality rates in several clinical conditions. We also critically review the therapeutic perspective of synthetic peptide adiponectin receptors agonist that has been postulated as a promising alternative for the treatment of metabolic syndrome and type 2 diabetes mellitus.
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Affiliation(s)
- Emilio Antonio Francischetti
- Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Rômulo Sperduto Dezonne
- Postgraduate Program in Translational Biomedicine, Grande Rio University, Duque de Caxias, Brazil
| | - Cláudia Maria Pereira
- Postgraduate Program in Translational Biomedicine, Grande Rio University, Duque de Caxias, Brazil
| | - Cyro José de Moraes Martins
- Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | | | | | - Virgínia Genelhu de Abreu
- Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
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Development of an Immune-Related Risk Signature in Patients with Bladder Urothelial Carcinoma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5848493. [PMID: 32884943 PMCID: PMC7455840 DOI: 10.1155/2020/5848493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/20/2020] [Accepted: 08/04/2020] [Indexed: 02/02/2023]
Abstract
With recent advances in immunooncology and tumor microenvironment, the treatment landscape of bladder urothelial carcinoma has been changing dramatically. We aim to construct an immune gene-related signature which can predict BLCA patients' overall survival. Transcriptomic data of BLCA patients was downloaded from The Cancer Genome Atlas database, and immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Prognostic immune-related genes were identified. We then constructed and validated an immune gene-related signature. Tumor-related transcription factors were downloaded from the Cistrome database, and a network between them and prognostic immune-related genes was generated. Cox's proportional hazards model and the Kaplan–Meier survival analysis were performed to assess our signature's prognostic ability. Relationship between the signature and patients' clinicopathologic features was then explored to validate its clinical value. We further downloaded concentration of six types of immune cells from the Tumor Immune Estimation Resource database to explore immune-related potential mechanisms of the signature.
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30
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Adipokines as key players in β cell function and failure. Clin Sci (Lond) 2020; 133:2317-2327. [PMID: 31769478 DOI: 10.1042/cs20190523] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 11/11/2019] [Accepted: 11/13/2019] [Indexed: 12/13/2022]
Abstract
The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the "classic" adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose-pancreatic β cell axis.
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O’Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA, Fink YA, Kapuria D, Cassimatis TM, Kelsey N, Cero C, Sater ZA, Piccinini F, Baskin AS, Leitner BP, Cai H, Millo CM, Dieckmann W, Walter M, Javitt NB, Rotman Y, Walter PJ, Ader M, Bergman RN, Herscovitch P, Chen KY, Cypess AM. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J Clin Invest 2020; 130:2209-2219. [PMID: 31961826 PMCID: PMC7190915 DOI: 10.1172/jci131126] [Citation(s) in RCA: 246] [Impact Index Per Article: 49.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 01/14/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).
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Affiliation(s)
- Alana E. O’Mara
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - James W. Johnson
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Joyce D. Linderman
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Robert J. Brychta
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Suzanne McGehee
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Laura A. Fletcher
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Yael A. Fink
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Devika Kapuria
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA
| | - Thomas M. Cassimatis
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Nathan Kelsey
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Cheryl Cero
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Zahraa Abdul Sater
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Francesca Piccinini
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Alison S. Baskin
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Brooks P. Leitner
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Hongyi Cai
- Clinical Mass Spectrometry Core, NIDDK, NIH, Bethesda, Maryland, USA
| | - Corina M. Millo
- Positron Emission Tomography Department, NIH, Bethesda, Maryland, USA
| | - William Dieckmann
- Positron Emission Tomography Department, NIH, Bethesda, Maryland, USA
| | - Mary Walter
- Clinical Laboratory Core, NIDDK, NIH, Bethesda, Maryland, USA
| | - Norman B. Javitt
- Departments of Medicine and Pediatrics, NYU School of Medicine, New York, New York, USA
| | - Yaron Rotman
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA
| | - Peter J. Walter
- Clinical Mass Spectrometry Core, NIDDK, NIH, Bethesda, Maryland, USA
| | - Marilyn Ader
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Richard N. Bergman
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Peter Herscovitch
- Positron Emission Tomography Department, NIH, Bethesda, Maryland, USA
| | - Kong Y. Chen
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
| | - Aaron M. Cypess
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA
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Naimo GD, Gelsomino L, Catalano S, Mauro L, Andò S. Interfering Role of ERα on Adiponectin Action in Breast Cancer. Front Endocrinol (Lausanne) 2020; 11:66. [PMID: 32132979 PMCID: PMC7041409 DOI: 10.3389/fendo.2020.00066] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 01/31/2020] [Indexed: 12/17/2022] Open
Abstract
Obesity is characterized by an excess of adipose tissue, due to adipocyte hypertrophy and hyperplasia. Adipose tissue is an endocrine organ producing many bioactive molecules, called adipokines. During obesity, dysfunctional adipocytes alter adipokine secretion, contributing to pathophysiology of obesity-associated diseases, including metabolic syndrome, type 2-diabetes, cardiovascular diseases and many types of malignancies. Circulating adiponectin levels are inversely correlated with BMI, thus adiponectin concentrations are lower in obese than normal-weight subjects. Many clinical investigations highlight that low adiponectin levels represent a serious risk factor in breast carcinogenesis, and are associated with the development of more aggressive phenotype. A large-scale meta-analysis suggests that BMI was positively associated with breast cancer mortality in women with ERα-positive disease, regardless menopausal status. This suggests the importance of estrogen signaling contribution in breast tumorigenesis of obese patients. It has been largely demonstrated that adiponectin exerts a protective role in ERα-negative cells, promoting anti-proliferative and pro-apoptotic effects, while controversial data have been reported in ERα-positive cells. Indeed, emerging data provide evidences that adiponectin in obese patients behave as growth factor in ERα-positive breast cancer cells. This addresses how ERα signaling interference may enhance the potential inhibitory threshold of adiponectin in ERα-positive cells. Thus, we may reasonably speculate that the relatively low adiponectin concentrations could be still not adequate to elicit, in ERα-positive breast cancer cells, the same inhibitory effects observed in ERα-negative cells. In the present review we will focus on the molecular mechanisms through which adiponectin affects breast cancer cell behavior in relationship to ERα expression.
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Affiliation(s)
- Giuseppina Daniela Naimo
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
| | - Luca Gelsomino
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
| | - Stefania Catalano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
| | - Loredana Mauro
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
- *Correspondence: Loredana Mauro
| | - Sebastiano Andò
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata, Italy
- Health Center, University of Calabria, Arcavacata, Italy
- Sebastiano Andò
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Adiyaman SC, Ozer M, Saydam BO, Akinci B. The Role of Adiponectin in Maintaining Metabolic Homeostasis. Curr Diabetes Rev 2020; 16:95-103. [PMID: 31267874 DOI: 10.2174/1573399815666190702155733] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 03/22/2019] [Accepted: 06/20/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Adiponectin is an adipocyte-derived cytokine closely associated with obesity, altered body adipose tissue distribution, insulin resistance, and cardiovascular diseases. INTRODUCTION Evidence from animal and human studies demonstrate that adiponectin plays an important role in the regulation of glucose and lipid metabolism. Adiponectin increases insulin sensitivity and improves systemic lipid metabolism. Although research efforts on adiponectin mostly aim towards its endocrine functions, this adipocyte-derived molecule also has profound autocrine and paracrine functions. CONCLUSION In this review, our aim is to discuss the role of adiponectin in maintaining metabolic homeostasis and its association with cardiovascular health. The proper identification of these roles is of great importance, which has the potential to identify a wealth of novel targets for the treatment of diabetes and related cardio-metabolic diseases.
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Affiliation(s)
| | - Muhammet Ozer
- Department of Internal Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Basak Ozgen Saydam
- Division of Endocrinology and Metabolism, Dokuz Eylul University, Izmir, Turkey
| | - Baris Akinci
- Division of Endocrinology and Metabolism, Dokuz Eylul University, Izmir, Turkey
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Pincombe NL, Pearson MJ, Smart NA, King N, Dieberg G. Effect of vitamin D supplementation on endothelial function - An updated systematic review with meta-analysis and meta-regression. Nutr Metab Cardiovasc Dis 2019; 29:1261-1272. [PMID: 31653512 DOI: 10.1016/j.numecd.2019.08.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 08/06/2019] [Accepted: 08/06/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Atherogenesis and endothelial dysfunction contribute to cardiovascular risk and vitamin D has been implemented in endothelial repair. This systematic review, meta-analysis and meta-regression aims to establish the effect of vitamin D supplementation on endothelial function. METHODS AND RESULTS To conduct the systematic review we searched the Cochrane Library of Controlled Trials, PubMed, ProQuest and EMBASE for randomized controlled trials that investigated the effects of vitamin D supplementation on flow-mediated dilation (FMD%), pulse wave velocity (PWV), and central augmentation index (AIx). Meta-analysis was based on a random effects model and inverse-variance methods to calculate either mean difference (MD) or standardized mean difference (SMD) as effects sizes. This was followed by meta-regression investigating the effect of baseline vitamin D concentrations, vitamin D dosing and study duration. Risk of bias was assessed using the JADAD scale and funnel plots. We identified 1056 studies of which 26 studies met inclusion criteria for quantitative analysis. Forty-two percent of the 2808 participants had either deficient or insufficient levels of vitamin D. FMD% (MD 1.17% (95% CI -0.20, 2.54), p = 0.095), PWV (SMD -0.09 m/s (95% CI -0.24, 0.07), p = 0.275) and AIx (SMD 0.05% (95% CI -0.1, 0.19), p = 0.52) showed no improvement with vitamin D supplementation. Sub-analysis and meta-regression revealed a tendency for AIx and FMD% to increase as weekly vitamin doses increased; no other significant relationships were identified. CONCLUSIONS Vitamin D supplementation showed no improvement in endothelial function. More evidence is required before recommendations for management of endothelial dysfunction can be made.
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Affiliation(s)
- Nick L Pincombe
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
| | - Melissa J Pearson
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
| | - Neil A Smart
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
| | - Nicola King
- School of Biomedical Sciences, Faculty of Medicine and Dentistry, University of Plymouth, Drake's Circus, Plymouth, PL4 8AA, UK
| | - Gudrun Dieberg
- School of Science and Technology, University of New England, Armidale, NSW 2351, Australia.
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Zhang C, Yang C, Li N, Liu X, He J, Chen X, Ding Y, Tong C, Peng C, Yin H, Wang Y, Gao R. Elevated insulin levels compromise endometrial decidualization in mice with decrease in uterine apoptosis in early-stage pregnancy. Arch Toxicol 2019; 93:3601-3615. [PMID: 31642978 DOI: 10.1007/s00204-019-02601-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 10/15/2019] [Indexed: 01/21/2023]
Abstract
Women with hyperinsulinism and insulin resistance have reduced fertility, but the underlying mechanism is still poorly understood. Aberrant endometrial decidualization in early pregnancy was linked to pregnancy complications. In this study, we aimed to test whether elevated insulin levels compromise decidualization in early-stage pregnancy. C57BL/6J mice in high insulin-exposed group were given a subcutaneous injection of recombinant insulin at a concentration of 0.05 IU daily. During decidualization in early pregnancy, serum levels of insulin, E2, P4, LH, FSH and blood glucose were significantly altered in mice treated with high insulin levels. The number of embryo implantation sites and endometrial decidual markers BMP2, ER, PR was significantly decreased by high insulin levels in vivo. Artificial decidual induction in primary mouse endometrial stromal cells and immortal human endometrial stromal cells line were all compromised after treated with 100 nmol/L insulin levels. All these results on flow cytometry, transmission electron microscopy and western blotting of Bax, Bcl2, cleaved Caspase3, cleaved PARP proteins level showed that decidual cells apoptosis was significantly decreased. Mitochondrial transmembrane potential also significantly increased by the influence of high insulin levels. PI3K and p-Akt were much higher after insulin exposure and the compromised decidualization by high insulin treatment was rescued by PI3K/Akt inhibitor LY294002 both in vitro and in vivo. In conclusion, we demonstrated that elevated insulin levels could compromise mice decidualization in early-stage pregnancy and PI3K/p-Akt-regulated apoptosis was essential for this role. It provides a clue for future investigation on compromised reproduction in women with hyperinsulinemia.
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Affiliation(s)
- Chen Zhang
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China.,Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Chengshun Yang
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Na Li
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Xueqing Liu
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Junlin He
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Xuemei Chen
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Yubin Ding
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Chao Tong
- Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China.,Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Chuan Peng
- Laboratory of Maternal and Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hubin Yin
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yingxiong Wang
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China
| | - Rufei Gao
- Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China. .,Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, 400016, China.
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Tan P, Mitra S, Amini F. Lifestyle Interventions for Weight Control Modified by Genetic Variation: A Review of the Evidence. Public Health Genomics 2019; 21:169-185. [DOI: 10.1159/000499854] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 03/23/2019] [Indexed: 11/19/2022] Open
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Hovland IH, Leikanger IS, Stokkeland O, Waage KH, Mjøs SA, Brokstad KA, McCann A, Ueland PM, Slizyte R, Carvajal A, Mellgren G, Remman T, Høgøy I, Gudbrandsen OA. Effects of low doses of fish and milk proteins on glucose regulation and markers of insulin sensitivity in overweight adults: a randomised, double blind study. Eur J Nutr 2019; 59:1013-1029. [DOI: 10.1007/s00394-019-01963-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 04/02/2019] [Indexed: 12/11/2022]
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Jhuo SJ, Tsai WC, Lee HC, Lin TH, Lee KT, Lai WT. Association between adiponectin T94G polymorphism and resistant hypertension in young-onset Taiwanese patients. Gene 2019; 689:161-165. [PMID: 30529101 DOI: 10.1016/j.gene.2018.11.094] [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: 08/15/2018] [Revised: 10/18/2018] [Accepted: 11/22/2018] [Indexed: 11/18/2022]
Abstract
Young-onset hypertensives (YOHs) with resistant hypertension (RH) have a greater long-term cardiovascular risk. The present study examined whether a functional adiponectin T94G polymorphism (rs2241766) is associated with RH in YOHs. We analyzed data from the Academia Sinica Collaborative Study on Hypertension Genetics in Taiwanese subjects to compare rs2241766 between YOHs with and without RH (≤50 years of age). RH was defined as the need for at least 3 drugs, including a diuretic to control blood pressure. Genotyping of rs2241766 was performed using TaqMan allelic discrimination. A total of 861 YOHs were enrolled and 54 had RH in enrolled population. For the rs2241766 in the allelic model, the odds ratio (OR) of RH allele frequency was 2.45 (p = 0.008), and there was a linear relationship between allele numbers and the presence of RH (p = 0.005). In multivariate analysis, the rs2241766 (OR = 2.766, p = 0.002), age (OR = 1.103, p = 0.001), uric acid (OR = 1.322, p = 0.001), high-sensitivity C-reactive protein (OR = 2.769, p = 0.001) and aldosterone (OR = 1.004, p = 0.001) were independently associated with the presence of RH. In the Taiwanese population, the adiponectin T94G polymorphism (rs2241766) is associated with RH in YOHs.
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Affiliation(s)
- Shih-Jie Jhuo
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chung Tsai
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Chun Lee
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hsien Lin
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Kun-Tai Lee
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Ter Lai
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Wrzosek M, Sawicka A, Wrzosek M, Piątkiewicz P, Tałałaj M, Nowicka G. Age at onset of obesity, transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism, adiponectin levels and the risk of type 2 diabetes in obese patients. Arch Med Sci 2019; 15:321-329. [PMID: 30899283 PMCID: PMC6425208 DOI: 10.5114/aoms.2017.69638] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 02/13/2017] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Interaction between obesity and genetic factors involved in the regulatory pathways of glucose homeostasis may play a significant role in diabetes development in the obese. The aim of this study was to investigate the associations between the TCF7L2 rs7903146 polymorphism, adiponectin levels, age at onset of obesity and the occurrence of type 2 diabetes (T2D) in a sample of obese Polish adults. MATERIAL AND METHODS A total of 474 unrelated obese subjects were included in this study. Real-time PCR was used to detect the TCF7L2 rs7903146 polymorphism. Serum level of adiponectin was determined by the ELISA method. Standard assays were used to measure total cholesterol, HDL cholesterol, triglycerides, glucose and HbA1c concentrations. We used multiple logistic regression to identify factors associated with type 2 diabetes. RESULTS We found that the T allele of rs7903146 was significantly associated with T2D risk (odds ratio of 1.59 for T allele, p = 0.005). This association persisted after adjusting for confounders in the recessive model (odds ratio of 3.54 for TT genotype, p = 0.011). Serum adiponectin levels were significantly lower in diabetic subjects than in nondiabetic individuals (3.6 vs. 5.6 µg/ml, p < 0.001). Participants who were obese at age ≥ 20 years had significantly higher odds of having T2D (OR = 4.94) than those with the onset of obesity before 20 years (p < 0.001). CONCLUSIONS Our study highlights the significance of the relationship between the TCF7L2 polymorphism, a person's age at onset of obesity and the prevalence of T2D, and confirms lower adiponectin levels in obese diabetics in comparison to obese nondiabetics.
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Affiliation(s)
- Małgorzata Wrzosek
- Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy and Center for Preclinical Studies, Medical University of Warsaw, Warsaw, Poland
| | - Ada Sawicka
- Department of Geriatrics, Internal Medicine and Metabolic Bone Diseases, Medical Centre of Postgraduate Education, Orlowski Hospital, Warsaw, Poland
| | - Michał Wrzosek
- Department of Internal Medicine and Diabetology, Medical University of Warsaw, Warsaw, Poland
| | - Paweł Piątkiewicz
- Department of Internal Medicine and Diabetology, Medical University of Warsaw, Warsaw, Poland
| | - Marek Tałałaj
- Department of Geriatrics, Internal Medicine and Metabolic Bone Diseases, Medical Centre of Postgraduate Education, Orlowski Hospital, Warsaw, Poland
| | - Grażyna Nowicka
- Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy and Center for Preclinical Studies, Medical University of Warsaw, Warsaw, Poland
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Khosravi-Largani M, Nojomi M, Aghili R, Otaghvar HA, Tanha K, Seyedi SHS, Mottaghi A. Evaluation of all Types of Metabolic Bariatric Surgery and its Consequences: a Systematic Review and Meta-Analysis. Obes Surg 2018; 29:651-690. [PMID: 30443720 DOI: 10.1007/s11695-018-3550-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Zhou Q, Xiang H, Li A, Lin W, Huang Z, Guo J, Wang P, Chi Y, Xiang K, Xu Y, Zhou L, So KF, Chen X, Sun X, Ren Y. Activating Adiponectin Signaling with Exogenous AdipoRon Reduces Myelin Lipid Accumulation and Suppresses Macrophage Recruitment after Spinal Cord Injury. J Neurotrauma 2018; 36:903-918. [PMID: 30221582 DOI: 10.1089/neu.2018.5783] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Myelin-laden macrophages (mye-MΦ), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. We found that in vitro activation of adiponectin receptors (AdipoRs) by their agonist AdipoRon suppressed myelin lipid accumulation in mye-MΦ through APPL1/PPARγ/LXRα/ABCA1-mediated lipid efflux, subsequently inhibiting inflammation and restoring normal function to mye-MΦ. In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-MΦ-mediated neuroinflammation in neurological disorders involving demyelination.
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Affiliation(s)
- Qishuang Zhou
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,4 Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hongkai Xiang
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,4 Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ang Li
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China.,5 Academician Workstation for Spinal Cord Injury, Kunming Tongren Hospital, Kunming, China
| | - Wu Lin
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhaoshui Huang
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Junxiu Guo
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China
| | - Pingjie Wang
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China
| | - Yijie Chi
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ke Xiang
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China
| | - Yunsheng Xu
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Libing Zhou
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China
| | - Kwok-Fai So
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China.,5 Academician Workstation for Spinal Cord Injury, Kunming Tongren Hospital, Kunming, China
| | - Xiaoming Chen
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xin Sun
- 2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China
| | - Yi Ren
- 1 Institute of Inflammation and Diseases, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou, China.,3 Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida
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Siti Hajar MH, Zulkefli S, Juwita S, Norhayati MN, Siti Suhaila MY, Rasool AHG, Harmy MY. Metabolic, inflammatory, and oxidative stress markers in women exposed to secondhand smoke. PeerJ 2018; 6:e5758. [PMID: 30356972 PMCID: PMC6196072 DOI: 10.7717/peerj.5758] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 09/14/2018] [Indexed: 12/20/2022] Open
Abstract
Background Secondhand smoke (SHS) exposure has adverse effects on the cardiovascular system. This study aimed to determine the effects of SHS on the cardiovascular disease biomarkers, namely the metabolic, inflammatory, and oxidative stress markers in healthy adult women. Methods This comparative cross-sectional study was conducted among healthy women. The cases included those women exposed to SHS, and the controls included those women not exposed to SHS. SHS exposure was defined as being exposed to SHS for at least 15 min for 2 days per week. Venous blood was taken to measure the metabolic markers (high molecular weight adiponectin, insulin level, insulin resistance, and nonesterified fatty acids), oxidative stress markers (oxidized low density lipoprotein cholesterol and 8-isoprostane), and inflammatory markers (high-sensitivity C-reactive protein and interleukin-6). A hair nicotine analysis was also performed. An analysis of covariance and a simple linear regression analysis were conducted. Results There were 101 women in the SHS exposure group and 91 women in the non-SHS exposure group. The mean (with standard deviation) of the hair nicotine levels was significantly higher in the SHS exposure group when compared to the non-SHS exposure group [0.22 (0.62) vs. 0.04 (0.11) ng/mg; P = 0.009]. No significant differences were observed in the high molecular weight adiponectin, insulin and insulin resistance, nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein between the two groups. The serum high molecular weight adiponectin was negatively associated with the insulin level and insulin resistance in the women exposed to SHS. However, no significant relationships were seen between the high molecular weight adiponectin and nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, high-sensitivity C-reactive protein in the SHS group. Discussion There were no significant differences in the metabolic, oxidative stress, and inflammatory markers between the SHS exposure and non-SHS exposure healthy women. A low serum level of high molecular weight adiponectin was associated with an increased insulin level and resistance in the women exposed to SHS.
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Affiliation(s)
- Mohd Hanaffi Siti Hajar
- Department of Family Medicine, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
| | - Sanip Zulkefli
- Central Research Laboratory, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
| | - Shaaban Juwita
- Department of Family Medicine, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
| | - Mohd Noor Norhayati
- Department of Family Medicine, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
| | - Mohd Yusoff Siti Suhaila
- Department of Family Medicine, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia
| | - Aida Hanum Ghulam Rasool
- Pharmacology Vascular Laboratory, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Mohamed Yusoff Harmy
- Faculty of Medicine and Health Sciences, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia
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Jafarirad S, Ayoobi N, Karandish M, Jalali MT, Haghighizadeh MH, Jahanshahi A. Dark Chocolate Effect on Serum Adiponectin, Biochemical and Inflammatory Parameters in Diabetic Patients: A Randomized Clinical Trial. Int J Prev Med 2018; 9:86. [PMID: 30450169 PMCID: PMC6202779 DOI: 10.4103/ijpvm.ijpvm_339_17] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 10/30/2017] [Indexed: 12/11/2022] Open
Abstract
Background: An appropriate snack for patients with diabetes mellitus should be considered to help them in their treatment due to their hard administrative diet. This study was conducted to evaluate the effect of dark chocolate on inflammatory markers, serum adiponectin, and certain biochemical factors in patients with type 2 diabetes (T2D). Methods: This study was a randomized parallel clinical trial. Thirty grams of 84% dark chocolate, along with therapeutic lifestyle changes (TLCs) guidelines, were administrated to patients with T2D. Control group received only TLC guidelines. The intervention period was 8 weeks. Twenty-one subjects in dark chocolate and 23 subjects in control group completed the study. Fasting blood samples were collected before and after the intervention period and inflammatory markers, biochemical factors, and adiponectin levels were assessed. Results: Fasting blood sugar, hemoglobin A1C, low-density lipoprotein and triglyceride levels declined significantly in the dark chocolate group and this decrease was significant between the intervention and control groups. Tumor necrosis factor-alpha, interleukin-6, and high sensitive C-reactive protein were significantly decreased in the dark chocolate group. Adiponectin levels were not significantly different between the two groups. Conclusions: In this study subjects who received dark chocolate along with TLC guidelines had lower levels of inflammatory markers such as hs-CRP, TNF-α, and IL-6, compared with the subjects who were devoid of dark chocolate and followed only the TLC guidelines. Other studies should be conducted to evaluate the most effective and administrative dosage of dark chocolate as a snack along with the common treatment of diabetes.
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Affiliation(s)
- Sima Jafarirad
- Nutrition and Metabolic Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Nutrition, School of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nina Ayoobi
- Nutrition and Metabolic Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Nutrition, School of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Majid Karandish
- Nutrition and Metabolic Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Nutrition, School of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad-Taha Jalali
- Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Alireza Jahanshahi
- Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Lee Y, Pędziwiatr M, Major P, Brar K, Doumouras AG, Hong D. The effect of omentectomy added to bariatric surgery on metabolic outcomes: a systematic review and meta-analysis of randomized controlled trials. Surg Obes Relat Dis 2018; 14:1766-1782. [PMID: 30228082 DOI: 10.1016/j.soard.2018.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 08/02/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND Excess visceral adipose tissue has been identified as an important risk factor for obesity-related co-morbidities. Conflicting information exists on whether omentectomy added to bariatric surgery is beneficial to metabolic variables. OBJECTIVE To evaluate the impact of omentectomy added to bariatric surgery on metabolic outcomes SETTING: University Hospital, Canada. METHODS MEDLINE, EMBASE, and PubMed were searched up to May 2018. Studies were eligible for inclusion if they were randomized controlled trials comparing omentectomy added to bariatric surgery with bariatric surgery alone. Primary outcome measures were absolute change in metabolic variables (body mass index, insulin, glucose, cholesterol, lipoproteins, and triglycerides); secondary outcomes were changes in adipocytokines. Pooled mean differences (mean deviation; MD) were calculated using random effects meta-analyses, and heterogeneity was quantified using the I2 statistic. RESULTS Ten trials involving a total of 366 patients met the inclusion criteria with a median follow-up time of 1 year after surgery. Adding omentectomy to bariatric surgery demonstrated a minimal but statistically significant decrease in body mass index compared with bariatric surgery alone (MD 1.29, 95% confidence interval .35-2.23, P = .007, I2 = 0%, 10 trials). Conversely, patients who underwent bariatric surgery alone had significant increases in high-density lipoprotein (MD -2.12, 95% confidence interval -4.13 to -.11, P = .04, I2 = 0%, 6 trials). Other metabolic outcomes and adipocytokines showed no significant difference between procedures. CONCLUSION The addition of omentectomy to bariatric surgery results in minimal reduction of body mass index. Considering no overall improvement in metabolic outcomes and the time and effort required, the therapeutic use of omentectomy added to bariatric surgery is not warranted.
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Affiliation(s)
- Yung Lee
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Michał Pędziwiatr
- 2nd Department of General Surgery, Jagiellonian University, Krakow, Poland; Centre for Research, Training and Innovation in Surgery (CERTAIN Surgery), Krakow, Poland
| | - Piotr Major
- 2nd Department of General Surgery, Jagiellonian University, Krakow, Poland; Centre for Research, Training and Innovation in Surgery (CERTAIN Surgery), Krakow, Poland
| | - Karanbir Brar
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Aristithes G Doumouras
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Dennis Hong
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
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45
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Li J, Liu YP. The roles of PPARs in human diseases. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 2018; 37:361-382. [PMID: 30036119 DOI: 10.1080/15257770.2018.1475673] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Peroxisome proliferator-activated receptors (PPARs), as members of nuclear hormone receptor superfamily, can be activated by binding natural or synthetic ligands. The use of related ligands has revealed many potential roles for PPARs in the pathogenesis of some human metabolic disorders and inflammatory-related disease. Based on the previous studies, this review primarily concluded the current progress of knowledge regarding the specific biological activity of PPARs in cancers, atherosclerosis, and type 2 diabetes mellitus, providing a foundation for the potential therapeutic use of PPAR ligands in human diseases.
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Affiliation(s)
- Jingjing Li
- a Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province , Sichuan Agricultural University , Chengdu , China
| | - Yi-Ping Liu
- a Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province , Sichuan Agricultural University , Chengdu , China
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46
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Clinical Applications of Adiponectin Measurements in Type 2 Diabetes Mellitus: Screening, Diagnosis, and Marker of Diabetes Control. DISEASE MARKERS 2018; 2018:5187940. [PMID: 30069271 PMCID: PMC6057311 DOI: 10.1155/2018/5187940] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 06/02/2018] [Indexed: 12/20/2022]
Abstract
Background Adipose tissue-derived adiponectin has pleiotropic protective effects with suppression of inflammatory and metabolic derangements that may result in insulin resistance, metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The aim of this study was to evaluate adiponectin as a diagnostic marker of T2DM and diabetes control. Methods Fasting adiponectin, insulin, glucose, and HbA1c were determined in 376 patients with known T2DM and 575 subjects with undiagnosed diabetes but with family history of T2DM. Clinical and anthropometric data were recorded. Subjects were classified on the basis of degree of adiposity, insulin resistance (IR), and achievement of target HbA1c levels. Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance for undiagnosed DM. Results In undiagnosed subjects, adiponectin was significantly lower in subjects with IR and diabetic subjects compared with those without. The area under the adiponectin ROC curve for diagnosis of DM was 0.740. In known T2DM subjects, those with good control had significantly higher adiponectin (8.6 versus 7.4 μg/mL) compared to subjects with poor control. Conclusions Adiponectin levels are associated with better glycemic control and could be a useful adjunct for screening for IR and T2DM. Therapeutic measures that increase adiponectin levels might be valuable targets for improving diabetes control and decreasing complications.
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47
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Kashiwagi R, Yamada Y, Ito Y, Mitsui Y, Sakaue T, Iwamoto R, Saisho K, Tamba S, Yamamoto K, Watanabe T, Fujimoto T, Iwahashi H, Matsuzawa Y. Increase in Adiponectin Level Prevents the Development of Type 2 Diabetes in Japanese Men With Low Adiponectin Levels. J Endocr Soc 2018; 2:753-764. [PMID: 29978152 PMCID: PMC6030829 DOI: 10.1210/js.2018-00033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 06/11/2018] [Indexed: 11/19/2022] Open
Abstract
Context Low serum adiponectin (Ad) level is an important risk factor for the development of type 2 diabetes mellitus (T2DM). Objective To determine whether the changes in Ad in subjects with low baseline serum Ad levels can reduce the rate of development of T2DM. Design/Setting/Participants We performed a large-scale longitudinal study of 7052 healthy Japanese men who underwent general health checkups more than twice between April 2007 and May 2015 at the Physical Check up Center, Sumitomo Hospital. The participants were divided into quartile groups according to baseline Ad level. Subjects of the lowest baseline Ad group (≤5.2 μg/mL) were subdivided into quartile subgroups according to the percent change in Ad (%ΔAd) and into two subgroups according to endpoint Ad (>5.2 and ≤5.2 μg/mL). Main Outcome Measures The cumulative incidence rate of T2DM. Results The cumulative incidence rate of T2DM of the lowest baseline Ad group (≤5.2 μg/mL) was significantly higher than the other quartile groups. The cumulative incidence rates of T2DM were significantly lower in the largest (≥21.5%) and the second largest (9.3% to 21.4%) %ΔAd-increased subgroups compared with the %ΔAd-decreased subgroup (P < 0.001 and P = 0.005, respectively). The cumulative incidence rates of T2DM were significantly lower in the endpoint Ad >5.2 μg/mL subgroup than in the ≤5.2 μg/mL subgroup (P < 0.001). Conclusions Increases in serum Ad levels of at least ~10% or >5.2 μg/mL can potentially reduce the risk of development of T2DM in Japanese men with low baseline Ad levels who are at a high risk of developing T2DM.
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Affiliation(s)
- Risa Kashiwagi
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Yuya Yamada
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Yoshito Ito
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Yuto Mitsui
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Takaaki Sakaue
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Ryuya Iwamoto
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Kenji Saisho
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Sachiko Tamba
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | - Koji Yamamoto
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
| | | | | | - Hiromi Iwahashi
- Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Yuji Matsuzawa
- Department of Endocrinology and Metabolism, Sumitomo Hospital, Osaka, Japan
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48
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Menzies-Gow NJ, Knowles EJ, Rogers I, Rendle DI. Validity and application of immunoturbidimetric and enzyme-linked immunosorbent assays for the measurement of adiponectin concentration in ponies. Equine Vet J 2018; 51:33-37. [DOI: 10.1111/evj.12960] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 03/31/2018] [Indexed: 01/24/2023]
Affiliation(s)
- N. J. Menzies-Gow
- Department of Clinical Sciences and Services; Royal Veterinary College; North Mymms Hertfordshire UK
| | - E. J. Knowles
- Department of Clinical Sciences and Services; Royal Veterinary College; North Mymms Hertfordshire UK
| | - I. Rogers
- Rainbow Equine Lab; Malton North Yorkshire UK
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49
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Choe EK, Yi JW, Chai YJ, Park KJ. Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer. J Surg Oncol 2018; 117:1833-1840. [DOI: 10.1002/jso.25078] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Accepted: 03/29/2018] [Indexed: 12/22/2022]
Affiliation(s)
- Eun K. Choe
- Department of Surgery; Seoul National University College of Medicine; Seoul Korea
- Department of Surgery; Seoul National University Hospital Healthcare System Gangnam Center; Seoul Korea
| | - Jin W. Yi
- Department of Surgery; Seoul National University College of Medicine; Seoul Korea
| | - Young J. Chai
- Department of Surgery; Seoul National University Boramae Medical Center; Seoul Korea
| | - Kyu J. Park
- Department of Surgery; Seoul National University College of Medicine; Seoul Korea
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50
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Cai C, Qian L, Jiang S, Sun Y, Wang Q, Ma D, Xiao G, Li B, Xie S, Gao T, Chen Y, Liu J, An X, Cui W, Li K. Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs. Oncotarget 2018; 8:34911-34922. [PMID: 28432282 PMCID: PMC5471021 DOI: 10.18632/oncotarget.16822] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 03/22/2017] [Indexed: 01/16/2023] Open
Abstract
Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn−/− ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn−/− pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue. Additionally, the serum insulin level decreased and the insulin sensitivity increased significantly in Mstn−/− pigs. Moreover, we found a significant increase in levels of insulin receptor and insulin receptor substrate proteins in skeletal muscle of Mstn−/− pigs, which then activating the insulin signaling pathway. Irisin-mediated regulation is not the only pathway for the activation of insulin signal in Mstn−/− skeletal muscle. This study provides valuable insight for the treatment of human obesity and diabetes mellitus.
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Affiliation(s)
- Chunbo Cai
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China.,State Key Laboratory of Agro Biotechnology, China Agricultural University, Beijing, 100193, P. R. China
| | - Lili Qian
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China.,State Key Laboratory of Agro Biotechnology, China Agricultural University, Beijing, 100193, P. R. China
| | - Shengwang Jiang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Youde Sun
- Institute of Animal Sciences, Qingdao, 266100, P. R. China
| | - Qingqing Wang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Dezun Ma
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Gaojun Xiao
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Biao Li
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Shanshan Xie
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Ting Gao
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China.,College of Animal Medicine, China Agricultural University, Beijing, 100193, P. R. China
| | - Yaoxing Chen
- College of Animal Medicine, China Agricultural University, Beijing, 100193, P. R. China
| | - Jie Liu
- Department of Bioengineering and Biotechnology, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, P. R. China
| | - Xiaorong An
- State Key Laboratory of Agro Biotechnology, China Agricultural University, Beijing, 100193, P. R. China
| | - Wentao Cui
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
| | - Kui Li
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
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