title: Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD.
abstract: 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 TGFβ 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.
authors.affiliation: Department of Nutrition, Auburn University, Auburn, Alabama;
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Bassett Research Institute, Bassett Medical Center, Cooperstown, New York;
authors.forename: Christine M
authors.initials: CM
authors.lastname: Burrington
authors.affiliation: College of Veterinary Medicine, Auburn University, Auburn, Alabama; and.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Graff
authors.affiliation: Department of Nutrition, Auburn University, Auburn, Alabama;
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Auburn University, Auburn, Alabama; and Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, Alabama;
authors.forename: Robert L
authors.initials: RL
authors.lastname: Judd
authors.affiliation: Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, and.
authors.forename: Promporn
authors.initials: P
authors.lastname: Suksaranjit
authors.affiliation: Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, and.
authors.forename: Quanhathai
authors.initials: Q
authors.lastname: Kaewpoowat
authors.affiliation: Department of Pathology, Bassett Medical Center, Cooperstown, New York.
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Davenport
authors.affiliation: Department of Nutrition, Auburn University, Auburn, Alabama;
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: O'Neill
authors.affiliation: Department of Nutrition, Auburn University, Auburn, Alabama; Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, Alabama; Bassett Research Institute, Bassett Medical Center, Cooperstown, New York; mwgreene@auburn.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Greene
mesh_terms: D052438:Adipocytes, White / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism*; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D059305:Diet, High-Fat; D066273:Diet, Western; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D005355:Fibrosis; D005632:Fructose; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006963:Hyperphagia; D015151:Immunoblotting; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D019422:Dietary Sucrose; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D005632:Fructose; D000410:Alanine Transaminase; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: NASH; adipose tissue; fructose; high-fat Western diet; insulin resistance