Effects of chronic sugar consumption on lipid accumulation and autophagy in the skeletal muscle.
OBJECTIVE
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.
Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125, Turin, Italy.
Daniela
D
De Stefanis
Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125, Turin, Italy. raffaella.mastrocola@unito.it.
Raffaella
http://orcid.org/0000-0002-0104-6129
R
Mastrocola
Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125, Turin, Italy.
Debora
D
Nigro
Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125, Turin, Italy.|Interuniversitary Institute of Myology, Chieti, Italy.
Paola
P
Costelli
Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125, Turin, Italy.
Manuela
M
Aragno
D000818:Animals; D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000097:blood / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D000071186:Beclin-1; D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014280:Triglycerides; D005632:Fructose; D005340:Fibrinogen; D002784:Cholesterol; D005947:Glucose
Autophagy; Fructose; Glucose; Intramyocellular lipids