title: The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases.
abstract: High-fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12-16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Williams
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Campbell
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Drew
authors.affiliation: Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Marburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Koch
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Hoggard
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: William D
authors.initials: WD
authors.lastname: Rees
authors.affiliation: Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Torkamol
authors.initials: T
authors.lastname: Kamolrat
authors.affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Ha
authors.initials: H
authors.lastname: Thi Ngo
authors.affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Inger-Lise
authors.initials: IL
authors.lastname: Steffensen
authors.affiliation: Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Gray
authors.affiliation: Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Marburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tups
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D002149:Energy Intake; D005786:Gene Expression Regulation / Q000187:drug effects*; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects
chemical_list: D004041:Dietary Fats