title: Diet-Induced Nonalcoholic Fatty Liver Disease Is Associated with Sarcopenia and Decreased Serum Insulin-Like Growth Factor-1.
abstract: 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 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.
  
  
  
  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).
  
  
  
  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.
authors: Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta #367, 833-0024, Santiago, Chile.|Departamento de Ciencias Químicas y Biológicas, Facultad de salud, Universidad Bernardo O'Higgins, Santiago, Chile.|Centro de Regeneración y Envejecimiento (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Daniel
authors: D
authors: Cabrera
authors: Instituto de Medicina, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors: Alex
authors: A
authors: Ruiz
authors: Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.|Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
authors: Claudio
authors: C
authors: Cabello-Verrugio
authors: Centro de Regeneración y Envejecimiento (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile.|Laboratorio de Diferenciación Celular y Patología, Departamento de Biología Celular y Molecular, MIFAB, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Enrique
authors: E
authors: Brandan
authors: Departamento de Ciencias Químicas y Biológicas, Facultad de salud, Universidad Bernardo O'Higgins, Santiago, Chile.
authors: Lisbell
authors: L
authors: Estrada
authors: Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta #367, 833-0024, Santiago, Chile.
authors: Margarita
authors: M
authors: Pizarro
authors: Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta #367, 833-0024, Santiago, Chile.
authors: Nancy
authors: N
authors: Solis
authors: Departamento de Patología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Javiera
authors: J
authors: Torres
authors: Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta #367, 833-0024, Santiago, Chile.
authors: Francisco
authors: F
authors: Barrera
authors: Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta #367, 833-0024, Santiago, Chile. marrese@med.puc.cl.|Centro de Regeneración y Envejecimiento (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile. marrese@med.puc.cl.
authors: Marco
authors: M
authors: Arrese
mesh_terms: D000818:Animals; D066273:Diet, Western; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D050152:Intra-Abdominal Fat; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology; D055948:Sarcopenia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain
chemical_list: D014280:Triglycerides; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D018995:Myosin Heavy Chains
keywords: Fructose; Insulin; Muscular atrophy; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Sarcopenia