Amelioration of fructose-induced hepatic lipid accumulation by vitamin D3 supplementation and high-intensity interval training in male Sprague‒Dawley rats

Lipids Health Dis. 2024 Nov 5;23(1):362. doi: 10.1186/s12944-024-02347-y.

Abstract

Background: Intrahepatic lipid accumulation (IHL), a hallmark of metabolic disorders, is closely associated with de novo lipogenesis (DNL). Notably, fructose feeding increased the DNL. Lifestyle modifications resulting from dietary changes and increased physical activity/exercise can decrease the IHL content. We examined the effects of vitamin D3 supplementation (VDS), high-intensity interval training (HIIT), and their combination on the transcription factors and enzymes of the DNL pathway in male Sprague‒Dawley rats fed a high-fructose diet (HFrD).

Methods: Forty male rats were assigned to 5 groups (n = 8): CS (the control group had a standard diet); CF (the control group had HFrD (10% (w/v) fructose solution in tap water)); and FT (HFrD + HIIT: 10 bouts of 4 min of high-intensity running, corresponding to 85-90% of the maximal speed with 2 min active rest periods of 50% maximal speed, 5 days per week); FD (HFrD + intervention of intraperitoneal injection of 10000 IU/kg/week VDS); FTD (HFrD + HIIT + VDS) that were maintained for 12 weeks. ELISA, the GOD-POD assay, folch, western blotting, and oil red O staining were used to determine insulin, fasting blood glucose (FBG), hepatic triglyceride (TG) and cholesterol levels; SREBP1c, ChREBP-β, ACC1, FASN, p-ACC1, AMPK, p-AMPK, and PKA protein expression; and IHL content, respectively.

Results: Both HIIT and VDS led to significant increases in the levels of PKA, AMPK, p-AMPK, and p-ACC1, as well as significant decreases in the levels of SREBP1c, ChREBP-β, ACC1, FASN, insulin, FBG, liver TG, liver cholesterol, and IHL. HIIT exhibited superior efficacy over VDS in reducing ChREBP-β, ACC1, insulin, FBG, liver TG and cholesterol, as well as increasing p-ACC1 and PKA. Notably, the combined intervention of HIIT and VDS yielded the most substantial improvements across all the parameters.

Conclusions: HFrD causes IHL accumulation and the onset of diabetes, whereas VDS and HIIT, along with their combined effects, prevent the consequences of HFrD.

Keywords: ACC1; ChREBP-β; FASN; High-intensity interval training; Intrahepatic lipid; SREBP1C.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / metabolism
  • Cholecalciferol* / pharmacology
  • Dietary Supplements*
  • Fructose*
  • High-Intensity Interval Training*
  • Lipid Metabolism / drug effects
  • Lipogenesis* / drug effects
  • Liver* / drug effects
  • Liver* / metabolism
  • Male
  • Physical Conditioning, Animal
  • Rats
  • Rats, Sprague-Dawley*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism

Substances

  • Fructose
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cholecalciferol
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • AMP-Activated Protein Kinases
  • Mlxipl protein, rat