期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 310, 期 6, 页码 E418-E439出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00319.2015
关键词
NASH; fructose; insulin resistance; high-fat Western diet; adipose tissue
资金
- Stephen C. Clark Fund
- E. Donnall Thomas Resident Research Fund
- Auburn University start-up funds
- USDA Hatch Grant [ALA043-1-13013]
nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition-ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD + F/S-fed mice. HFWD + F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGF beta gene expression. Furthermore, HWFD + F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD + F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.
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