title: Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice.
abstract: The high-fat, high-sucrose diet (HFSD)-fed C57Bl/6 mouse is a widely used model of prediabetes. However, studies typically implement a relatively short dietary intervention lasting between 4 and 16 weeks; as a result, little is known about how a long-term HFSD influences the metabolic profile of these mice. Therefore, the aim of this investigation was to examine the effects of consuming a HFSD for 42 weeks on the development of hyperinsulinaemia and glucose intolerance in male C57Bl/6 mice. Two cohorts of HFSD mice were studied at independent institutes and they underwent an oral glucose tolerance test (OGTT) with measures of plasma insulin and free fatty acids (FFA). Age-matched chow-fed control mice were also studied. The HFSD-fed mice were hyperinsulinaemic and grossly obese, being over 25 g heavier than chow-fed mice, which was due to a marked expansion of subcutaneous adipose tissue. This was associated with a 3-fold increase in liver lipid content. Glucose tolerance, however, was either the same or better than control mice due to the preservation of glucose disposal as revealed by a dynamic stable isotope-labelled OGTT. In addition, plasma FFAs were suppressed to lower levels in HFSD mice during the OGTT. In conclusion, we have made the paradoxical observation that long-term HFSD feeding results in the resolution of glucose intolerance in the C57Bl/6 mouse. Mechanistically, we propose that the gross expansion of subcutaneous adipose tissue increases the glucose disposal capacity of the HFSD-fed mouse, which overcomes the prevailing insulin resistance to improve glucose tolerance.
authors.affiliation: Institute for Physical Activity and NutritionSchool of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.
authors.forename: Greg M
authors.initials: GM
authors.lastname: Kowalski
authors.affiliation: Haematopoiesis and Leukocyte Biology LaboratoryBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.|Department of MedicineColumbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kraakman
authors.affiliation: Institute for Physical Activity and NutritionSchool of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.
authors.forename: Shaun A
authors.initials: SA
authors.lastname: Mason
authors.affiliation: Haematopoiesis and Leukocyte Biology LaboratoryBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: Institute for Physical Activity and NutritionSchool of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia clinton.bruce@deakin.edu.au.
authors.forename: Clinton R
authors.initials: CR
authors.lastname: Bruce
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D006946:Hyperinsulinism / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced; D013395:Sucrose / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D013395:Sucrose; D005947:Glucose
keywords: diet-induced obesity; glucose tolerance; high-fat; high-sucrose diet; insulin resistance