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

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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. 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). 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 16weeks. In addition, we determined muscle fiber size and strength of limb skeletal muscle, myosin heavy chain (MHC) protein levels, and IGF-1 serum levels. Westernized diet feeding was associated with weight gain, increased visceral fat mass (epididymal pad weight: 0.76g±0.13 vs. 0.33±0.27g; p=0.0023), hepatic steatosis (HTC: 118.2±6.88mg/g liver vs. 43.26±5.63mg/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 (0-30μm) and a decreased proportion of high-diameter muscle fibers (60-90μm), 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±20.04pg/ml) compared with chow-fed mice (366.0±12.42pg/ml, p<0.05). 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.