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J Endocrinol. 2017 Jun;233(3):269-279. doi: 10.1530/JOE-17-0004. Epub 2017 Mar 30.

Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice.

Author information

1
Institute for Physical Activity and NutritionSchool of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.
2
Haematopoiesis and Leukocyte Biology LaboratoryBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
3
Department of MedicineColumbia University College of Physicians and Surgeons, New York, New York, USA.
4
Institute for Physical Activity and NutritionSchool of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia clinton.bruce@deakin.edu.au.

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.

KEYWORDS:

diet-induced obesity; glucose tolerance; high-fat; high-sucrose diet; insulin resistance

PMID:
28360081
DOI:
10.1530/JOE-17-0004
[Indexed for MEDLINE]

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