Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet

Lipids Health Dis. 2019 Jan 5;18(1):6. doi: 10.1186/s12944-018-0933-z.

Abstract

Objective: To emphasize the mechanism of concurrent exercise effect on lipid disorders in insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD).

Materials and methods: Twenty male ApoE knockout mice were randomly divided into two groups: HFD group (n = 10) fed a high fat diet, and HFDE group (n = 10) with high-fat diet intervention for 12 weeks and swimming exercise. Other ten healthy male C57BL/6 J mice were fed a normal diet, and included as control group. Retro-orbital blood samples were collected for biochemical analysis. Oil red O staining of liver tissues was performed to confirm the exercise effect. Western blotting was performed to evaluate the expressions of PPAR-γ, CPT-1, MCAD.

Results: The levels of TG, TC, LDL, FFA, FIN, FPG and Homa-IRI in the HFD group were significantly higher than ND group, while these were markedly decreased in the HFDE group compared with HFD group. The Oil Red O staining of liver samples further confirmed the exercise effect on the change of lipid deposition in the liver. Western blotting showed increased expressions of PPAR-γ, CPT-1, MCAD induced by high fat diet were significantly downregulated by exercise.

Conclusion: A concurrent 12-week exercise protocol alleviated the lipid metabolism disorders of IR and NAFLD, probably via PPAR-γ/CPT-1/MCAD signaling.

Keywords: CPT-1; Concurrent exercise; Insulin resistance; MCAD; Non-alcoholic fatty liver disease; PPAR-γ.

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Cadherins / agonists
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carnitine O-Palmitoyltransferase / genetics*
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diet, High-Fat / adverse effects
  • Fatty Acids, Nonesterified / blood
  • Gene Expression Regulation
  • Insulin Resistance
  • Lipid Metabolism / genetics*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / therapy*
  • PPAR gamma / agonists
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Physical Conditioning, Animal*
  • Signal Transduction
  • Swimming
  • Triglycerides / blood

Substances

  • Apolipoproteins E
  • Cadherins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids, Nonesterified
  • PPAR gamma
  • Triglycerides
  • M-cadherin
  • CPT1B protein, mouse
  • Carnitine O-Palmitoyltransferase