Effects of chronic sugar consumption on lipid accumulation and autophagy in the skeletal muscle

Eur J Nutr. 2017 Feb;56(1):363-373. doi: 10.1007/s00394-015-1086-8. Epub 2015 Oct 20.


Purpose: In recent years, the increasing consumption of soft drinks containing high-fructose corn syrup or sucrose has caused a rise in fructose intake, which has been related to the epidemic of metabolic diseases. As fructose and glucose intake varies in parallel, it is still unclear what the effects of the increased consumption of the two single sugars are. In the present study, the impact of chronic consumption of glucose or fructose on skeletal muscle of healthy mice was investigated.

Methods: C57BL/6J male mice received water (C), 15 % fructose (ChF) or 15 % glucose (ChG) to drink for up to 7 months. Lipid metabolism and markers of inflammation and autophagy were assessed in gastrocnemius muscle.

Results: Increased body weight and gastrocnemius muscle mass, as well as circulating glucose, insulin, and lipid plasma levels were observed in sugar-drinking mice. Although triglycerides increased in the gastrocnemius muscle of both ChF and ChG mice (+32 and +26 %, vs C, respectively), intramyocellular lipids accumulated to a significantly greater extent in ChF than in ChG animals (ChF +10 % vs ChG). Such perturbations were associated with increased muscle interleukin-6 levels (threefold of C) and with the activation of autophagy, as demonstrated by the overexpression of LC3B-II (ChF, threefold and ChG, twofold of C) and beclin-1 (ChF, sevenfold and ChG, tenfold of C).

Conclusions: The present results suggest that intramyocellular lipids and the pro-inflammatory signaling could contribute to the onset of insulin resistance and lead to the induction of autophagy, which could be an adaptive response to lipotoxicity.

Keywords: Autophagy; Fructose; Glucose; Intramyocellular lipids.

MeSH terms

  • Animals
  • Autophagy*
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Disease Models, Animal
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Fructose / administration & dosage
  • Fructose / adverse effects*
  • Glucose / administration & dosage
  • Glucose / adverse effects*
  • Insulin / blood
  • Insulin Resistance
  • Interleukin-6 / blood
  • Lipid Metabolism / drug effects*
  • Male
  • Metabolic Diseases / blood
  • Metabolic Diseases / chemically induced
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Suppressor of Cytokine Signaling 3 Protein / blood
  • Suppressor of Cytokine Signaling 3 Protein / genetics
  • Triglycerides / blood


  • Beclin-1
  • Blood Glucose
  • Insulin
  • Interleukin-6
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Triglycerides
  • Fructose
  • Fibrinogen
  • Cholesterol
  • Glucose