MiPsummer Programme pdf - Mitochondrial Physiology Society

77
Abstract # 45
Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves
metabolic health.
Loes P M Duivenvoorde, Evert M van Schothorst, Annelies Bunschoten and Jaap Keijer
Human and Animal Physiology, Wageningen University, Wageningen, the Netherlands.
Jaap.keijer@wur.nl
Background High energy intake and, specifically, high dietary fat intake challenge the mammalian
metabolism and correlate with many metabolic disorders such as obesity and diabetes. Dietary
restriction (DR) is known to prevent the development of metabolic disorders. The current western
diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat diet elicits
similar beneficial effects on health.
Objective: To assess health beneficial responses of DR of a HFD
Methods: C57BL/6J mice were given either an libitum moderate high fat diet (30 en %; HF) or 30
% restriction of the same diet (HF-DR). Metabolic parameters were analysed and whole genome
microarray analysis of white adipose tissue (WAT) was performed.
Results. Already after five weeks of restriction, the serum levels of cholesterol and leptin were
significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin
levels were increased. The body weight and measured serum parameters remained stable in the
following 7 weeks of restriction, implying metabolic adaptation. Gene expression in WAT was
strongly influenced by HF-DR; in total, 8643 genes were differentially expressed between both
groups of mice, with a major role for genes involved in lipid metabolism, mitochondrial functioning
and metabolic flexibility. This was confirmed by quantitative real-time reverse transcription-PCR
and substantiated by increase in mitochondrial density in WAT of HF-DR mice.
Conclusions. DR of HF improves health parameters and gene expression profiles related to
substrate efficiency and metabolic flexibility. This is associated with increased mitochondrial
density, which may be a marker for adipose tissue health.
Journal of Molecular Endocrinology (2011) 47, 81–97