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Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.

ABSTRACT: Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies. Thus, the role that FGF21 plays in mediating the positive metabolic effects of exercise in AT are unclear. In this study, FGF21-knockout (KO) mice were used to directly assess the role of FGF21 in mediating the metabolic and anti-inflammatory effects of exercise on white AT (WAT) and brown AT (BAT). Male FGF21KO and wild-type mice were provided running wheels or remained sedentary for 8 weeks (n?=?9-15/group) and compared for adiposity, insulin sensitivity (i.e., HOMA-IR, Adipo-IR) and AT inflammation and metabolic function (e.g., mitochondrial enzyme activity, subunit content). Adiposity and Adipo-IR were increased in FGF21KO mice and decreased by EX. The BAT of FGF21KO animals had reduced mitochondrial content and decreased relative mass, both normalized by EX. WAT and BAT inflammation was elevated in FGF21KO mice, reduced in both genotypes by EX. EX increased WAT Pgc1alpha gene expression, citrate synthase activity, COX I content and total AMPK content in WT but not FGF21KO mice. Collectively, these findings reveal a previously unappreciated anti-inflammatory role for FGF21 in WAT and BAT, but do not support that FGF21 is necessary for EX-mediated anti-inflammatory effects.

SUBMITTER: Porter JW

PROVIDER: S-EPMC5581275 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.

Porter Jay W JW Rowles Joe L JL Fletcher Justin A JA Zidon Terese M TM Winn Nathan C NC McCabe Leighton T LT Park Young-Min YM Perfield James W JW Thyfault John P JP Rector R Scott RS Padilla Jaume J Vieira-Potter Victoria J VJ

The Journal of endocrinology 20170801 2

Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels ...[more]

PMID: 28765264

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Project description:Background: Improved glycemic control and cardiovascular function are major benefits of regular exercise training (ET) in type 2 diabetes. Recent work has demonstrated that ET improves cardiac and vascular functions independent of obesity, inflammation, and glucose control in the diabetic db/db mouse. In this study, we determined whether ET can overcome the effects of elevated inflammatory cytokines and hyperglycemia on markers of cardiac angiogenesis and inflammation in the diabetic mouse. Methods: Male diabetic db/db mice were assigned to a sedentary and exercise-trained group. Sedentary lean control littermates were used as controls. ET was performed at moderate intensity on a treadmill 5 days a week for a period of 8 weeks. After ET, blood was collected for assay of glucose, hemoglobin (HB and HB1AC), C-reactive protein (CRP), and IL-6. Markers of inflammation and insulin resistance (IL-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) and angiogenesis (endothelial nitric oxide synthase [eNOS], vascular endothelial growth factor-A [VEGF-A], and hypoxia-inducible factor-1α [HIF-1α]) were measured in hearts. Results: Diabetic db/db mice remained obese and hyperglycemic after ET. Percent total HB and HB1AC were significantly higher in ET db/db mice compared to sedentary db/db mice, indicating further deterioration of glucose control with ET. Plasma levels of CRP and IL-6 were higher in sedentary db/db mice compared to control mice and were unaffected by ET. However, in the presence of hyperglycemia and elevated plasma cytokines, protein expression of eNOS, mRNA expression of VEGF-A, and HIF-1α was increased in db/db hearts after ET. On the other hand, protein expression of TNF-α and mRNA expression IL-6 and IL-1β was significantly decreased by ET in hearts of db/db mice. Conclusion: Our results indicate that ET improves cardiac markers of angiogenesis, insulin resistance, and endothelial dysfunction in the db/db mouse. This was observed independently of obesity, hyperglycemia, and the systemic inflammatory state.

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Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.

Publications

Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21.

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