4.7 Article

Swimming exercise ameliorates insulin resistance and nonalcoholic fatty liver by negatively regulating PPARγ transcriptional network in mice fed high fat diet

Journal

MOLECULAR MEDICINE
Volume 29, Issue 1, Pages -

Publisher

SPRINGER
DOI: 10.1186/s10020-023-00740-4

Keywords

Swimming exercise; Insulin resistance; Non-alcoholic fatty liver disease; PPAR gamma signaling; Lipid metabolism

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This study demonstrates that swimming exercise can improve lipid metabolism in insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) through modulation of PPAR gamma signaling in the liver of mice.
Background Recent findings elucidated hepatic PPAR gamma functions as a steatogenic-inducer gene that activates de novo lipogenesis, and is involved in regulation of glucose homeostasis, lipid accumulation, and inflammation response. This study delved into a comprehensive analysis of how PPAR gamma signaling affects the exercise-induced improvement of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD), along with its underlying mechanism.Methods Chronic and acute swimming exercise intervention were conducted in each group mice. IR status was assessed by GTT and ITT assays. Serum inflammatory cytokines were detected by Elisa assays. PPAR gamma and its target genes expression were detected by qPCR assay. Relative protein levels were quantified via Western blotting. ChIP-qPCR assays were used to detect the enrichment of PPAR gamma on its target genes promoter.Results Through an exploration of a high-fat diet (HFD)-induced IR and NAFLD model, both chronic and acute swimming exercise training led to significant reductions in body weight and visceral fat mass, as well as hepatic lipid accumulation. The exercise interventions also demonstrated a significant amelioration in IR and the inflammatory response. Meanwhile, swimming exercise significantly inhibited PPAR gamma and its target genes expression induced by HFD, containing CD36, SCD1 and PLIN2. Furthermore, swimming exercise presented significant modulation on regulatory factors of PPAR gamma expression and transcriptional activity.Conclusion The findings suggest that swimming exercise can improve lipid metabolism in IR and NAFLD, possibly through PPAR gamma signaling in the liver of mice.

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