Diet-Induced Nonalcoholic Fatty Liver Disease Is Associated with Sarcopenia and Decreased Serum Insulin-Like Growth Factor-1.

Cabrera D.; Ruiz A.; , Cabello-Verrugio C.; Brandan E.; , Estrada L.; Pizarro M.; Solis N.; Torres J.; Barrera F.; Arrese M.

Keywords: insulin, nonalcoholic steatohepatitis, fructose, nonalcoholic fatty liver disease, sarcopenia, Muscular atrophy


BACKGROUND: Decreased muscle mass or sarcopenia has been associated with nonalcoholic fatty liver disease (NAFLD). However, the functional consequences of this association and its pathogenesis remain ill-defined. AIMS: To evaluate muscle mass and function in a diet-induced NAFLD mouse model and explore its association with changes in serum insulin-like growth factor-1 (IGF-1). METHODS: Weight gain, visceral fat, serum biochemical parameters, liver histology, and hepatic triglyceride content (HTC) were assessed in C57/Bl6 mice fed a westernized diet during 16 weeks. In addition, we determined muscle fiber size and strength of limb skeletal muscle, myosin heavy chain (MHC) protein levels, and IGF-1 serum levels. RESULTS: Westernized diet feeding was associated with weight gain, increased visceral fat mass (epididymal pad weight: 0.76 g ± 0.13 vs. 0.33 ± 0.27 g; p = 0.0023), hepatic steatosis (HTC: 118.2 ± 6.88 mg/g liver vs. 43.26 ± 5.63 mg/g<, p < 0.05), and necroinflammation (histological scores: 1.29 ± 0.42 vs. 4.00 ± 0.53<, p < 0.05). Also, mice fed the experimental diet had an increased proportion of low-diameter muscle fibers (0-30 μm) and a decreased proportion of high-diameter muscle fibers (60-90 μm), which correlated with decreased MHC protein levels, consistent with significant muscle atrophy. Functional studies showed that mice fed a westernized diet had reduced muscle strength and lower serum levels of IGF-1 (284.2 ± 20.04 pg/ml) compared with chow-fed mice (366.0 ± 12.42 pg/ml, p < 0.05). CONCLUSION: Experimental NAFLD is associated with sarcopenia, decreased muscle strength, and reduced IGF-1 serum levels. IGF-1 reduction may be involved in pathogenesis of NAFLD-associated sarcopenia.

Más información

Título de la Revista: Digestive Disease Sci.
Volumen: 61
Número: 11
Fecha de publicación: 2017
Página de inicio: 3190
Página final: 3198
Idioma: english
Notas: ISI