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Chen WC, Chang TC, Perera L, Cheng MH, Hong JJ, Cheng CM. Pilot study on the impact of HIFU treatment on miRNA profiles in vaginal secretions of uterine fibroids and adenomyosis patients. Int J Hyperthermia 2024; 41:2418426. [PMID: 39462514 DOI: 10.1080/02656736.2024.2418426] [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: 08/11/2024] [Revised: 09/29/2024] [Accepted: 10/14/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND High intensity focused ultrasound (HIFU) ablation treatment for uterine fibroids and adenomyosis has been long developed. The aim of this study is to investigate miRNA profile changes in vaginal secretions after HIFU treatment and their clinical relevance. METHODS We prospectively collected vaginal secretions samples from 8 patients (1 with adenomyosis and 7 with fibroids) before and after HIFU treatment. RNA was isolated and miRNA profiles were analyzed using next-generation sequencing (NGS) sequencing. RESULTS Our study showed miRNA profile change in vaginal secretion samples after HIFU treatment for uterine fibroids/adenomyosis, with 33 miRNAs upregulated and 6 downregulated overall. In fibroid cases, 31 miRNAs were upregulated and 7 downregulated, while in adenomyosis case, 41 miRNAs were upregulated and 71 downregulated. Four miRNAs (hsa-miR-7977, hsa-miR-155-5p, hsa-miR-191-5p, hsa-miR-223-3p) showed significant differences after HIFU treatment in fibroid cases, except in case 5 with the lowest treatment sonications (425 sonications) and energy input (170000 J). hsa-miR-7977 consistently showed downregulation after HIFU treatment. hsa-miR-155-5p were downregulated in case 4 with lowest treatment efficiency (2439.64 J/cm3), while they were upregulated in other cases. hsa-miR-191-5p and hsa-miR-223-3p were downregulated in cases 4 and 7, with case 7 influenced by high sonication and energy due to multiple fibroids. CONCLUSIONS HIFU treatment altered miRNA profiles in fibroids/adenomyosis patients. Notably, hsa-miR-7977, hsa-miR-155-5p, hsa-miR-191-5p, and hsa-miR-223-3p showed significant changes in fibroid cases, except in low-energy treatments. hsa-miR-7977 consistently decreased post-treatment, while hsa-miR-155-5p decreased in the least efficient cases. Further research is needed for validation.
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Affiliation(s)
- Wei-Chun Chen
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Obstetrics and Gynecology, New Taipei City Municipal Tucheng Hospital, New Taipei City, Taiwan
- International Intercollegiate Ph.D. Program & Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
- HIFU Treatment Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ting-Chang Chang
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- HIFU Treatment Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Lynn Perera
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Mei-Hsiu Cheng
- Taiwan Business Development Department, Inti Taiwan, Inc, Hsinchu, Taiwan
| | - Jun-Jie Hong
- Taiwan Business Development Department, Inti Taiwan, Inc, Hsinchu, Taiwan
| | - Chao-Min Cheng
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
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Unger CA, Aladhami AK, Hope MC, Cotham WE, Nettles KW, Clegg DJ, Velázquez KT, Enos RT. Skeletal Muscle Endogenous Estrogen Production Ameliorates the Metabolic Consequences of a High-Fat Diet in Male Mice. Endocrinology 2023; 164:bqad105. [PMID: 37421340 PMCID: PMC10368313 DOI: 10.1210/endocr/bqad105] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/20/2023] [Accepted: 07/06/2023] [Indexed: 07/10/2023]
Abstract
AIMS The role of skeletal muscle estrogen and its ability to mitigate the negative impact of a high-fat diet (HFD) on obesity-associated metabolic impairments is unknown. To address this, we developed a novel mouse model to determine the role of endogenous 17β-estradiol (E2) production in males in skeletal muscle via inducible, skeletal muscle-specific aromatase overexpression (SkM-Arom↑). METHODS Male SkM-Arom↑ mice and littermate controls were fed a HFD for 14 weeks prior to induction of SkM-Arom↑ for a period of 6.5 weeks. Glucose tolerance, insulin action, adipose tissue inflammation, and body composition were assessed. Indirect calorimetry and behavioral phenotyping experiments were performed using metabolic cages. Liquid chromatography mass spectrometry was used to determine circulating and tissue (skeletal muscle, hepatic, and adipose) E2 and testosterone concentrations. RESULTS SkM-Arom↑ significantly increased E2 in skeletal muscle, circulation, the liver, and adipose tissue. SkM-Arom↑ ameliorated HFD-induced hyperglycemia, hyperinsulinemia, impaired glucose tolerance, adipose tissue inflammation, and reduced hepatic lipid accumulation while eliciting skeletal muscle hypertrophy. CONCLUSION Enhanced skeletal muscle aromatase activity in male mice induces weight loss, improves metabolic and inflammatory outcomes and mitigates the negative effects of a HFD. Additionally, our data demonstrate for the first time skeletal muscle E2 has anabolic effects on the musculoskeletal system.
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Affiliation(s)
- Christian A Unger
- Department of Pathology, Microbiology, and Immunology, University of South Carolina-School of Medicine, Columbia, SC 29209, USA
| | - Ahmed K Aladhami
- Department of Pathology, Microbiology, and Immunology, University of South Carolina-School of Medicine, Columbia, SC 29209, USA
- University of Baghdad, Nursing College, Baghdad, Iraq
| | - Marion C Hope
- Department of Pathology, Microbiology, and Immunology, University of South Carolina-School of Medicine, Columbia, SC 29209, USA
| | - William E Cotham
- Department of Chemistry and Biochemistry, College of Arts and Science, University of South Carolina, Columbia, SC 29209, USA
| | - Kendall W Nettles
- Department of Integrative Structural and Computational Biology, Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA
| | - Deborah J Clegg
- Department of Internal Medicine, Texas Tech Health Sciences Center, El Paso, TX 79905, USA
| | - Kandy T Velázquez
- Department of Pathology, Microbiology, and Immunology, University of South Carolina-School of Medicine, Columbia, SC 29209, USA
| | - Reilly T Enos
- Department of Pathology, Microbiology, and Immunology, University of South Carolina-School of Medicine, Columbia, SC 29209, USA
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Changes in subcutaneous adipose tissue microRNA expression in response to exercise training in obese African women. Sci Rep 2022; 12:18408. [PMID: 36319747 PMCID: PMC9626597 DOI: 10.1038/s41598-022-23290-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
Abstract
The mechanisms that underlie exercise-induced adaptations in adipose tissue have not been elucidated, yet, accumulating studies suggest an important role for microRNAs (miRNAs). This study aimed to investigate miRNA expression in gluteal subcutaneous adipose tissue (GSAT) in response to a 12-week exercise intervention in South African women with obesity, and to assess depot-specific differences in miRNA expression in GSAT and abdominal subcutaneous adipose tissue (ASAT). In addition, the association between exercise-induced changes in miRNA expression and metabolic risk was evaluated. Women underwent 12-weeks of supervised aerobic and resistance training (n = 19) or maintained their regular physical activity during this period (n = 12). Exercise-induced miRNAs were identified in GSAT using Illumina sequencing, followed by analysis of differentially expressed miRNAs in GSAT and ASAT using quantitative real-time PCR. Associations between the changes (pre- and post-exercise training) in miRNA expression and metabolic parameters were evaluated using Spearman's correlation tests. Exercise training significantly increased the expression of miR-155-5p (1.5-fold, p = 0.045), miR-329-3p (2.1-fold, p < 0.001) and miR-377-3p (1.7-fold, p = 0.013) in GSAT, but not in ASAT. In addition, a novel miRNA, MYN0617, was identified in GSAT, with low expression in ASAT. The exercise-induced differences in miRNA expression were correlated with each other and associated with changes in high-density lipoprotein concentrations. Exercise training induced adipose-depot specific miRNA expression within subcutaneous adipose tissue depots from South African women with obesity. The significance of the association between exercise-induced miRNAs and metabolic risk warrants further investigation.
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Shree N, Ding Z, Flaws J, Choudhury M. Role of microRNA in Endocrine Disruptor-Induced Immunomodulation of Metabolic Health. Metabolites 2022; 12:1034. [PMID: 36355117 PMCID: PMC9695656 DOI: 10.3390/metabo12111034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 01/22/2025] Open
Abstract
The prevalence of poor metabolic health is growing exponentially worldwide. This condition is associated with complex comorbidities that lead to a compromised quality of life. One of the contributing factors recently gaining attention is exposure to environmental chemicals, such as endocrine-disrupting chemicals (EDCs). Considerable evidence suggests that EDCs can alter the endocrine system through immunomodulation. More concerning, EDC exposure during the fetal development stage has prominent adverse effects later in life, which may pass on to subsequent generations. Although the mechanism of action for this phenomenon is mostly unexplored, recent reports implicate that non-coding RNAs, such as microRNAs (miRs), may play a vital role in this scenario. MiRs are significant contributors in post-transcriptional regulation of gene expression. Studies demonstrating the immunomodulation of EDCs via miRs in metabolic health or towards the Developmental Origins of Health and Disease (DOHaD) Hypothesis are still deficient. The aim of the current review was to focus on studies that demonstrate the impact of EDCs primarily on innate immunity and the potential role of miRs in metabolic health.
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Affiliation(s)
- Nitya Shree
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University (TAMU), College Station, TX 77843, USA
| | - Zehuan Ding
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University (TAMU), College Station, TX 77843, USA
| | - Jodi Flaws
- Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA
| | - Mahua Choudhury
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University (TAMU), College Station, TX 77843, USA
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Aladhami AK, Unger CA, Hope MC, Cotham WE, Velázquez KT, Enos RT. Augmenting Skeletal Muscle Estrogen Does not Prevent or Rescue Obesity-linked Metabolic Impairments in Female Mice. Endocrinology 2022; 163:6678809. [PMID: 36039699 DOI: 10.1210/endocr/bqac146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Indexed: 11/19/2022]
Abstract
AIMS We developed a novel mouse model with increased skeletal muscle estrogen content via inducible, skeletal-muscle-specific aromatase overexpression (SkM-Arom↑). We proposed to examine the effect that increased skeletal muscle estrogen both in gonadally intact and ovariectomized (OVX) female mice has on preventing or rescuing high-fat diet (HFD)-induced obesity. METHODS In the prevention experiment, gonadally intact and OVX SkM-Arom↑ mice and littermate controls were fed a low-fat diet (LFD) or HFD for 13 weeks. SkM-Arom↑ was induced at the initiation of dietary treatment. In the intervention experiment, gonadally intact and OVX SkM-Arom↑ mice and littermate controls were fed an HFD for 14 weeks before induction of SkM-Arom↑ for 6 weeks. Glucose tolerance, insulin action, adipose tissue inflammation, and body composition were assessed. Liquid chromatography-mass spectrometry was used to determine circulating and skeletal muscle steroid content. RESULTS SkM-Arom↑ significantly increased skeletal muscle 17β-estradiol (E2) and estrone (E1) in both experiments. Interestingly, this resulted in leakage of estrogens into circulation, producing a physiologically relevant E2 concentration. Consequently, bone mineral density (BMD) was enhanced and adipose tissue inflammation was reduced in the prevention experiment only. However, no benefits were seen with respect to changes in adiposity or metabolic outcomes. CONCLUSION We show that increasing skeletal muscle estrogen content does not provide a metabolic benefit in gonadally intact and OVX female mice in the setting of obesity. However, a chronic physiological concentration of circulating E2 can improve BMD and reduce adipose tissue inflammation independently of a metabolic benefit or changes in adiposity.
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Affiliation(s)
- Ahmed K Aladhami
- Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
- University of Baghdad, Nursing College, Baghdad, Iraq
| | - Christian A Unger
- Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
| | - Marion C Hope
- Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
| | - William E Cotham
- Department of Chemistry and Biochemistry, College of Arts and Science, University of South Carolina, Columbia, South Carolina 29208, USA
| | - Kandy T Velázquez
- Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
| | - Reilly T Enos
- Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
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Congenital adiponectin deficiency mitigates high-fat-diet-induced obesity in gonadally intact male and female, but not in ovariectomized mice. Sci Rep 2022; 12:16668. [PMID: 36198723 PMCID: PMC9534911 DOI: 10.1038/s41598-022-21228-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 09/23/2022] [Indexed: 11/24/2022] Open
Abstract
Epidemiological literature indicates that women are less susceptible to type II diabetes (T2D) than males. The general consensus is that estrogen is protective, whereas its deficiency in post-menopause is associated with adiposity and impaired insulin sensitivity. However, epidemiological data suggests that males are more prone to developing T2D, and at a lower BMI, compared to females during post-menopausal years; suggesting that another factor, other than estrogen, protects females. We proposed to determine if adiponectin (APN) serves as this protective factor. An initial experiment was performed in which gonadally intact male and female mice were fed either a purified low-fat diet (LFD) or high-fat diet (HFD) (40% kcals from fat) for 16 weeks. An additional group of HFD ovariectomy (OVX) mice were included to assess estrogen deficiency’s impact on obesity. Body composition, adipose tissue inflammation, ectopic lipid accumulation as well as glucose metabolism and insulin resistance were assessed. In corroboration with previous data, estrogen deficiency (OVX) exacerbated HFD-induced obesity in female mice. However, despite a higher body fat percentage and a similar degree of hepatic and skeletal muscle lipid accumulation, female OVX HFD-fed mice exhibited enhanced insulin sensitivity relative to HFD-fed males. Therefore, a subsequent HFD experiment was performed utilizing male and female (both gonadally intact and OVX) APN deficient mice (APN−/−) and wildtype littermates to determine if APN is the factor which protects OVX females from the similar degree of metabolic dysfunction as males in the setting of obesity. Indirect calorimetry was used to determine observed phenotype differences. APN deficiency limited adiposity and mitigated HFD-induced insulin resistance and adipose tissue inflammation in gonadally intact male and female, but not in OVX mice. Using indirect calorimetry, we uncovered that slight, but non-statistically significant differences in food intake and energy expenditure leading to a net difference in energy balance likely explain the reduced body weight exhibited by male APN-deficient mice. In conclusion, congenital APN deficiency is protective against obesity development in gonadally intact mice, however, in the setting of estrogen deficiency (OVX) this is not true. These findings suggest that gonadal status dictates the protective effects of congenital APN deficiency in the setting of HFD-induced obesity.
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de Sousa Neto IV, Durigan JLQ, da Silva ASR, de Cássia Marqueti R. Adipose Tissue Extracellular Matrix Remodeling in Response to Dietary Patterns and Exercise: Molecular Landscape, Mechanistic Insights, and Therapeutic Approaches. BIOLOGY 2022; 11:biology11050765. [PMID: 35625493 PMCID: PMC9138682 DOI: 10.3390/biology11050765] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 04/19/2022] [Accepted: 04/26/2022] [Indexed: 12/20/2022]
Abstract
Simple Summary Adipose tissue is considered a metabolic organ that adjusts overall energy homeostasis and critical hormones to the body’s needs. In conditions of caloric intake surpassing energy expenditure, lipid accumulation occurs with constant extracellular matrix deposition. Excess lipids and adipocyte hypertrophy may reduce extracellular matrix flexibility in conjunction with hypoxia and inflammation. These processes induce the development of adipose tissue fibrosis and correlated metabolic dysfunctions, such as insulin resistance. With the increasing rate of chronic diseases worldwide, it is essential to generate a more precise knowledge of fibrotic processes, as well as to create optimal models to study potential therapies to combat the harmful effects of extracellular matrix deposition. In this work, we focused on the physiological processes in the remodeling of adipose tissue fibrosis, along with their relevance to clinical indications. Furthermore, we emphasize understanding how lifestyle can alleviate adipocyte dysfunction. Several studies showed that a nutritionally balanced diet combined with exercise is a remarkable potential strategy for lipolytic activity, preventing rapid extracellular matrix expansion in parallel with insulin and glucose action improvements. Thus, the emerging beneficial role of exercise training and low-calorie diet on adipose tissue ECM remodeling is a topic that deserves attention from health professionals. Abstract The extracellular matrix (ECM) is a 3-dimensional network of molecules that play a central role in differentiation, migration, and survival for maintaining normal homeostasis. It seems that ECM remodeling is required for adipose tissue expansion. Despite evidence indicating that ECM is an essential component of tissue physiology, adipose tissue ECM has received limited attention. Hence, there is great interest in approaches to neutralize the harmful effects of ECM enlargement. This review compiles and discusses the current literature on adipose tissue ECM remodeling in response to different dietary patterns and exercise training. High-calorie diets result in substantial adipose tissue ECM remodeling, which in turn could lead to fibrosis (excess deposition of collagens, elastin, and fibronectin), inflammation, and the onset of metabolic dysfunction. However, combining a nutritionally balanced diet with exercise is a remarkable potential strategy for lipolytic activity, preventing rapid ECM expansion in different adipose tissue depots. Despite the distinct exercise modalities (aerobic or resistance exercise) reversing adipose tissue fibrosis in animal models, the beneficial effect on humans remains controversial. Defining molecular pathways and specific mechanisms that mediate the positive effects on adipose tissue, ECM is essential in developing optimized interventions to improve health and clinical outcomes.
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Affiliation(s)
- Ivo Vieira de Sousa Neto
- Molecular Analysis Laboratory, Faculty of Ceilândia, Universidade de Brasília, Brasília 70910-900, Brazil; or
- Correspondence:
| | | | - Adelino Sanchez Ramos da Silva
- Graduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto 14040-900, Brazil;
- School of Physical Education and Sport of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-900, Brazil
| | - Rita de Cássia Marqueti
- Molecular Analysis Laboratory, Faculty of Ceilândia, Universidade de Brasília, Brasília 70910-900, Brazil; or
- Graduate Program in Rehabilitation Sciences, Universidade de Brasília, Brasília 70910-900, Brazil;
- Graduate Program in Health Sciences and Technology, Universidade de Brasília, Brasília 70910-900, Brazil
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Aladhami AK, Unger CA, Ennis SL, Altomare D, Ji H, Hope MC, Velázquez KT, Enos RT. Macrophage tumor necrosis factor-alpha deletion does not protect against obesity-associated metabolic dysfunction. FASEB J 2021; 35:e21665. [PMID: 34131955 PMCID: PMC8716064 DOI: 10.1096/fj.202100543rr] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/29/2021] [Accepted: 04/30/2021] [Indexed: 01/11/2023]
Abstract
The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), has been suggested to be a key factor in the induction of obesity-associated metabolic dysfunction. However, the role that macrophage-derived TNF-α has on regulating metabolic perturbations in obesity is not completely understood. Therefore, we utilized the TNF-αFlox/Flox(F/F) , LyzMcre± mouse model to determine the impact that macrophage TNF-α deletion has on the development of high-fat diet (HFD)-induced obesity. At 10 weeks of age, male littermates were randomly assigned to 1 of 4 groups: TNF-αF/F low-fat diet (TNF-αF/F LFD), TNF-αF/F,LyzMCre LFD, TNF-αF/F HFD, or TNF-αF/F,LyzMCre HFD (n = 16-28/group) and were fed their respective diets for 18 weeks. Body weight was assessed throughout the course of the experiment. Body composition, hepatic lipid accumulation, and metabolic outcomes were also examined. A microarray gene expression experiment was performed from RNA isolated from epididymal adipose tissue of the HFD-fed groups (n = 10/group) and results were verified via qRT-PCR for all groups. Macrophage-derived TNF-α deletion significantly reduced adipose tissue TNF-α gene expression and circulating TNF-α and downregulated genes linked to the toll-like receptor (TLR) and NFκB signaling pathways. However, macrophage TNF-α deletion had no effect on hindering the development of obesity, hepatic lipid accumulation, or improving glucose metabolism or insulin sensitivity. In conclusion, macrophage-derived TNF-α is not a causative factor for the induction of obesity-associated metabolic dysfunction.
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Affiliation(s)
- Ahmed K. Aladhami
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
- Nursing College, University of Baghdad, Baghdad, Iraq
| | - Christian A. Unger
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Shannon L. Ennis
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Diego Altomare
- Department of Drug Discovery and Biomedical Sciences, University of South Carolina College of Pharmacy, Columbia, SC, USA
| | - Hao Ji
- Department of Drug Discovery and Biomedical Sciences, University of South Carolina College of Pharmacy, Columbia, SC, USA
| | - Marion C. Hope
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Kandy T. Velázquez
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Reilly T. Enos
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
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Yin JL, Wu Y, Yuan ZW, Gao XH, Chen HD. Advances in scarless foetal wound healing and prospects for scar reduction in adults. Cell Prolif 2020; 53:e12916. [PMID: 33058377 PMCID: PMC7653265 DOI: 10.1111/cpr.12916] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/25/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023] Open
Abstract
Healing after mammalian skin injury involves the interaction between numerous cellular constituents and regulatory factors, which together form three overlapping phases: an inflammatory response, a proliferation phase and a remodelling phase. Any slight variation in these three stages can substantially alter the healing process and resultant production of scars. Of particular significance are the mechanisms responsible for the scar‐free phenomenon observed in the foetus. Uncovering such mechanisms would offer great expectations in the treatment of scars and therefore represents an important area of investigation. In this review, we provide a comprehensive summary of studies on injury‐induced skin regeneration within the foetus. The information contained in these studies provides an opportunity for new insights into the treatment of clinical scars based on the cellular and molecular processes involved.
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Affiliation(s)
- Jia-Li Yin
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning, China.,National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan Wu
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning, China.,National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zheng-Wei Yuan
- Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
| | - Xing-Hua Gao
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning, China.,National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Hong-Duo Chen
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning, China.,National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, Shenyang, Liaoning, China
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Sougiannis AT, VanderVeen BN, Cranford TL, Enos RT, Velazquez KT, McDonald S, Bader JE, Chatzistamou I, Fan D, Murphy EA. Impact of weight loss and partial weight regain on immune cell and inflammatory markers in adipose tissue in male mice. J Appl Physiol (1985) 2020; 129:909-919. [PMID: 32853106 DOI: 10.1152/japplphysiol.00356.2020] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Weight fluctuations are common among individuals with obesity and are associated with increased morbidity. We examined adipose tissue immune and inflammatory markers in mice following weight loss and partial weight regain. Male C57BL/6 mice were randomized into four groups (n = 8-10/group): low-fat diet for 32 wk (LFD), high-fat diet for 32 wk (HFD), LFD for 28 wk and then changed to a HFD for 4 wk (LFD→H), and HFD for 21 wk and then changed to LFD for 7 wk and then changed to HFD for 4 wk (HFD→L→H). LFD→H and HFD→L→H mice did not differ in body weight, fat mass, or fat percentage; however, these parameters were greater than in LFD (P < 0.05) but lower than in HFD (P < 0.05). HFD→L→H mice had smaller adipocytes than HFD and LFD→H (P < 0.05) but not LFD mice. Expressions of CD11c and CD8a genes were elevated in epididymal fat of HFD→L→H compared with LFD→H and LFD (P < 0.05)mice. However, CD11c was lower in HFD→L→H than in HFD mice (P < 0.05), but there was no difference in CD8a between these groups. TNFα and IFNγ expressions were increased in HFD→L→H compared with LFD and LFD→H mice (P < 0.05), although HFD→L→H had lower expression of these cytokines than HFD (P < 0.05). IL-1β was greater in HFD→L→H compared with LFD (P < 0.05) but was not different from LFD→H or HFD mice. Monocyte chemoattractant protein-1 was lower (P < 0.05) in HFD→L→H than in LFD→H. These data reinforce the importance of maintaining a body weight in the range that is recommended for optimal health to reduce immune and inflammatory perturbations associated with obesity.NEW & NOTEWORTHY We examined the immune and inflammatory status of adipose tissue in mice after they underwent weight loss followed by partial weight regain. We show an increase in selected immune cells and inflammatory mediators, in high-fat diet-fed mice that had prior exposure to a high-fat diet. Although weight fluctuations appear to exacerbate immune cell abundance and inflammation in adipose tissue, severity is less than in mice that were exposed to sustained high-fat diet feedings.
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Affiliation(s)
- Alexander T Sougiannis
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Brandon N VanderVeen
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Taryn L Cranford
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Reilly T Enos
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Kandy T Velazquez
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Sierra McDonald
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Jackie E Bader
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Ioulia Chatzistamou
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Daping Fan
- Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - E Angela Murphy
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
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DeBari MK, Abbott RD. Adipose Tissue Fibrosis: Mechanisms, Models, and Importance. Int J Mol Sci 2020; 21:ijms21176030. [PMID: 32825788 PMCID: PMC7503256 DOI: 10.3390/ijms21176030] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/15/2020] [Accepted: 08/17/2020] [Indexed: 02/06/2023] Open
Abstract
Increases in adipocyte volume and tissue mass due to obesity can result in inflammation, further dysregulation in adipose tissue function, and eventually adipose tissue fibrosis. Like other fibrotic diseases, adipose tissue fibrosis is the accumulation and increased production of extracellular matrix (ECM) proteins. Adipose tissue fibrosis has been linked to decreased insulin sensitivity, poor bariatric surgery outcomes, and difficulty in weight loss. With the rising rates of obesity, it is important to create accurate models for adipose tissue fibrosis to gain mechanistic insights and develop targeted treatments. This article discusses recent research in modeling adipose tissue fibrosis using in vivo and in vitro (2D and 3D) methods with considerations for biomaterial selections. Additionally, this article outlines the importance of adipose tissue in treating other fibrotic diseases and methods used to detect and characterize adipose tissue fibrosis.
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Affiliation(s)
- Megan K. DeBari
- Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA;
| | - Rosalyn D. Abbott
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
- Correspondence:
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Caslin HL, Hasty AH. Extrinsic and Intrinsic Immunometabolism Converge: Perspectives on Future Research and Therapeutic Development for Obesity. Curr Obes Rep 2019; 8:210-219. [PMID: 30919312 PMCID: PMC6661206 DOI: 10.1007/s13679-019-00344-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Research over the past decade has shown that immunologic and metabolic pathways are intricately linked. This burgeoning field of immunometabolism includes intrinsic and extrinsic pathways and is known to be associated with obesity-accelerated metabolic disease. Intrinsic immunometabolism includes the study of fuel utilization and bioenergetic pathways that influence immune cell function. Extrinsic immunometabolism includes the study of immune cells and products that influence systemic metabolism. RECENT FINDINGS Th2 immunity, macrophage iron handling, adaptive immune memory, and epigenetic regulation of immunity, which all require intrinsic metabolic changes, play a role in systemic metabolism and metabolic function, linking the two arms of immunometabolism. Together, this suggests that targeting intrinsic immunometabolism can directly affect immune function and ultimately systemic metabolism. We highlight important questions for future basic research that will help improve translational research and provide therapeutic targets to help establish new treatments for obesity and associated metabolic disorders.
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Affiliation(s)
- Heather L Caslin
- Molecular Physiology and Biophysics, Vanderbilt University, 813 Light Hall, 23rd Ave. South and Pierce, Nashville, TN, 37232, USA
| | - Alyssa H Hasty
- Molecular Physiology and Biophysics, Vanderbilt University, 813 Light Hall, 23rd Ave. South and Pierce, Nashville, TN, 37232, USA.
- VA Tennessee Valley Healthcare System, Nashville, TN, USA.
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13
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Velázquez KT, Enos RT, Bader JE, Sougiannis AT, Carson MS, Chatzistamou I, Carson JA, Nagarkatti PS, Nagarkatti M, Murphy EA. Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice. World J Hepatol 2019; 11:619-637. [PMID: 31528245 PMCID: PMC6717713 DOI: 10.4254/wjh.v11.i8.619] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 07/05/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments.
AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD.
METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD) (14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.
RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice.
CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients.
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Affiliation(s)
- Kandy T Velázquez
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Reilly T Enos
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Jackie E Bader
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Alexander T Sougiannis
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Meredith S Carson
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Ioulia Chatzistamou
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - James A Carson
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
- College of Health Professions, University of Tennessee Health Sciences Center, Memphis, TN 38163, United States
| | - Prakash S Nagarkatti
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Mitzi Nagarkatti
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - E Angela Murphy
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
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14
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Sougiannis AT, VanderVeen BN, Enos RT, Velazquez KT, Bader JE, Carson M, Chatzistamou I, Walla M, Pena MM, Kubinak JL, Nagarkatti M, Carson JA, Murphy EA. Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota. Brain Behav Immun 2019; 80:44-55. [PMID: 30807838 PMCID: PMC6660349 DOI: 10.1016/j.bbi.2019.02.020] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/30/2019] [Accepted: 02/20/2019] [Indexed: 12/13/2022] Open
Abstract
Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.
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Affiliation(s)
- A T Sougiannis
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - B N VanderVeen
- Department of Exercise Science, School of Public Health, University of South Carolina, SC 29201, USA
| | - R T Enos
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - K T Velazquez
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - J E Bader
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - M Carson
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - I Chatzistamou
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - M Walla
- Department of Chemistry, University of South Carolina, SC 29201, USA
| | - M M Pena
- Department of Biology, University of South Carolina, SC 29201, USA
| | - J L Kubinak
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - M Nagarkatti
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA
| | - J A Carson
- College of Health Professions, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - E A Murphy
- Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, SC 29209, USA.
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15
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Ebrahimi R, Bahiraee A, Niazpour F, Emamgholipour S, Meshkani R. The role of microRNAs in the regulation of insulin signaling pathway with respect to metabolic and mitogenic cascades: A review. J Cell Biochem 2019; 120:19290-19309. [PMID: 31364207 DOI: 10.1002/jcb.29299] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 06/27/2019] [Indexed: 12/18/2022]
Abstract
Insulin resistance (IR) is a shared pathological condition among type 2 diabetes, obesity, cardiovascular disease, and other metabolic disorders. It is growing significantly all over the world and consequently, a substantial effort is needed for developing the potential novel diagnostics and therapeutics. An insulin signaling pathway is tightly modulated by different mechanisms including the epigenetic modifications. Today, a deal of great attention has been shifted towards the regulatory role of noncoding RNAs on target proteins of the insulin signaling pathway. Noncoding RNAs are a major area of the epigenetics which control gene expression at the posttranscriptional levels and include a large class of microRNAs (miRNAs). With this in view, many studies have implicated the mediatory effects of miRNAs on the downstream metabolic and mitogenic proteins of the insulin signaling pathway. Since providing new biomarkers for the early diagnosis of IR and related metabolic traits are very significant, we intended to review the possible role of miRNAs in the regulation of the insulin signaling pathway, with a primary focus on the downstream target proteins of the metabolic and mitogenic cascades.
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Affiliation(s)
- Reyhane Ebrahimi
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Bahiraee
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Farshad Niazpour
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Solaleh Emamgholipour
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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16
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Bader JE, Enos RT, Velázquez KT, Carson MS, Sougiannis AT, McGuinness OP, Robinson CM, Murphy EA. Repeated clodronate-liposome treatment results in neutrophilia and is not effective in limiting obesity-linked metabolic impairments. Am J Physiol Endocrinol Metab 2019; 316:E358-E372. [PMID: 30576244 PMCID: PMC6415716 DOI: 10.1152/ajpendo.00438.2018] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Depletion of macrophages is thought to be a therapeutic option for obesity-induced inflammation and metabolic dysfunction. However, whether the therapeutic effect is a direct result of reduced macrophage-derived inflammation or secondary to decreases in fat mass is controversial, as macrophage depletion has been shown to disrupt energy homeostasis. This study was designed to determine if macrophage depletion via clodronate-liposome (CLD) treatment could serve as an effective intervention to reduce obesity-driven inflammatory and metabolic impairments independent of changes in energy intake. After 16 wk on a high-fat diet (HFD) or the AIN-76A control (low-fat) diet (LFD) ( n = 30/diet treatment), male C57BL/6J mice were assigned to a CLD- or PBS-liposome treatment ( n = 15/group) for 4 wk. Liposomes were administered biweekly via intraperitoneal injections (8 administrations in total). PBS-liposome-treated groups were pair-fed to their CLD-treated dietary counterparts. Metabolic function was assessed before and after liposome treatment. Adipose tissue, as well as the liver, was investigated for macrophage infiltration and the presence of inflammatory mediators. Additionally, a complete blood count was performed. CLD treatment reduced energy intake. When controlling for energy intake, CLD treatment was unable to regress metabolic dysfunction or nonalcoholic fatty liver disease and impaired adipose tissue insulin action. Moreover, repeated CLD treatment induced neutrophilia and anemia, increased adipose tissue mRNA expression of the proinflammatory cytokines IL-6 and IL-1β, and augmented circulating IL-6 and monocyte chemoattractant protein-1 concentrations ( P < 0.05). This study suggests that repeated intraperitoneal administration of CLD to deplete macrophages attenuates obesity by limiting energy intake. Moreover, after controlling for the benefits of weight loss, the accompanying detrimental side effects limit regular CLD treatment as an effective therapeutic strategy.
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Affiliation(s)
- Jackie E Bader
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina
| | - Reilly T Enos
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina
| | - Kandy T Velázquez
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina
| | - Meredith S Carson
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina
| | - Alex T Sougiannis
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina
| | - Owen P McGuinness
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine , Nashville, Tennessee
| | - Cory M Robinson
- Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University , Morgantown, West Virginia
| | - E Angela Murphy
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina
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17
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Padmanaban V, Prakash SS. Strain, Diet, and Gender Influence the Role of miR155 in Diabetes Mellitus. Indian J Endocrinol Metab 2018; 22:570-572. [PMID: 30148111 PMCID: PMC6085968 DOI: 10.4103/ijem.ijem_125_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- V. Padmanaban
- Department of Biochemistry, Christian Medial College, Vellore, Tamil Nadu, India
| | - S. S. Prakash
- Department of Biochemistry, Christian Medial College, Vellore, Tamil Nadu, India
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18
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Velázquez KT, Enos RT, Carson MS, Cranford TL, Bader JE, Sougiannis AT, Pritchett C, Fan D, Carson JA, Murphy EA. miR155 deficiency aggravates high-fat diet-induced adipose tissue fibrosis in male mice. Physiol Rep 2017; 5:e13412. [PMID: 28947593 PMCID: PMC5617927 DOI: 10.14814/phy2.13412] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 07/18/2017] [Accepted: 08/14/2017] [Indexed: 02/06/2023] Open
Abstract
Noncoding RNAs are emerging as regulators of inflammatory and metabolic processes. There is evidence to suggest that miRNA155 (miR155) may be linked to inflammation and processes associated with adipogenesis. We examined the impact of global miRNA-155 deletion (miR155-/-) on the development of high-fat diet (HFD)-induced obesity. We hypothesized that loss of miR155 would decrease adipose tissue inflammation and improve the metabolic profile following HFD feedings. Beginning at 4-5 weeks of age, male miR155-/- and wild-type (WT) mice (n = 13-14) on a C57BL/6 background were fed either a HFD or low-fat diet for 20 weeks. Body weight was monitored throughout the study. Baseline and terminal body composition was assessed by DEXA analysis. Adipose tissue mRNA expression (RT-qPCR) of macrophage markers (F4/80, CD11c, and CD206) and inflammatory mediators (MCP-1 and TNF-α) as well as adiponectin were measured along with activation of NFκB-p65 and JNK and PPAR-γ Adipose tissue fibrosis was assessed by picrosirius red staining and western blot analysis of Collagen I, III, and VI. Glucose metabolism and insulin resistance were assessed by Homeostatic Model Assessment - Insulin Resistance (HOMA-IR), and a glucose tolerance test. Compared to WT HFD mice, miR155-/- HFD mice displayed similar body weights, yet reduced visceral adipose tissue accumulation. However, miR155-/- HFD displayed exacerbated adipose tissue fibrosis and decreased PPAR-γ protein content. The loss of miR155 did not affect adipose tissue inflammation or glucose metabolism. In conclusion, miR155 deletion did not attenuate the development of the obese phenotype, but adipose tissue fibrosis was exacerbated, possibly through changes to adipogenic processes.
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Affiliation(s)
- Kandy T Velázquez
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Reilly T Enos
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Meredith S Carson
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Taryn L Cranford
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Jackie E Bader
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Alexander T Sougiannis
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Cara Pritchett
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - Daping Fan
- Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina
| | - James A Carson
- Department of Exercise Science, University of South Carolina, Columbia, South Carolina
| | - E Angela Murphy
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina
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