Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD

Yuwen Luo; Christine M Burrington; Emily C Graff; Jian Zhang; Robert L Judd; Promporn Suksaranjit; Quanhathai Kaewpoowat; Samantha K Davenport; Ann Marie O'Neill; Michael W Greene

doi:10.1152/ajpendo.00319.2015

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Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD

Journal article

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Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD

Yuwen Luo, Christine M Burrington, Emily C Graff, Jian Zhang, Robert L Judd, Promporn Suksaranjit, Quanhathai Kaewpoowat, Samantha K Davenport, Ann Marie O'Neill and Michael W Greene

American journal of physiology: endocrinology and metabolism, Vol.310(6), pp.E418-E439

03/15/2016

DOI: 10.1152/ajpendo.00319.2015

PMCID: PMC4796265

PMID: 26670487

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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.

Adipocytes, White - pathology

Adipose Tissue, White - metabolism

Alanine Transaminase - metabolism

Animals

Collagen Type I - genetics

Collagen Type III - genetics

Diet, High-Fat

Diet, Western

Dietary Sucrose

Disease Models, Animal

Fibrosis

Fructose

Glycogen Synthase Kinase 3 - metabolism

Glycogen Synthase Kinase 3 beta

Hyperphagia

Immunoblotting

Insulin Resistance

Liver - metabolism

Liver - pathology

Macrophages

Male

Mice

Mice, Inbred C57BL

Non-alcoholic Fatty Liver Disease - genetics

Non-alcoholic Fatty Liver Disease - metabolism

Obesity - genetics

Obesity - metabolism

Organ Size

Phenotype

Proto-Oncogene Proteins c-akt

Transcriptome

Transforming Growth Factor beta - genetics

Triglycerides - metabolism

Details

Title: Subtitle: Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD
Creators: Yuwen Luo - Auburn University
Christine M Burrington - Bassett Medical Center
Emily C Graff - Auburn University
Jian Zhang - Auburn University
Robert L Judd - Auburn University
Promporn Suksaranjit - Bassett Medical Center
Quanhathai Kaewpoowat - Bassett Medical Center
Samantha K Davenport - Bassett Medical Center
Ann Marie O'Neill - Auburn University
Michael W Greene - Bassett Medical Center
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.310(6), pp.E418-E439
DOI: 10.1152/ajpendo.00319.2015
PMID: 26670487
PMCID: PMC4796265
ISSN: 0193-1849
eISSN: 1522-1555
Grant note: T35 OD010991 / NIH HHS
Language: English
Date published: 03/15/2016
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984359876002771

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