Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice

Esther Donga,Louis M. Havekes,Johannes A. Romijn,Eleonora P.M. Corssmit,Annemieke C. Heijboer,Zhi-Chao Dang,Peter J. Voshol

doi:10.1194/jlr.m400440-jlr200

Abstract

Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA expression of metabolically relevant genes. Sixteen hours of fasting did not show an effect on hepatic insulin sensitivity in terms of glucose production in the presence of increased hepatic TG content. In muscle, however, fasting resulted in increased insulin sensitivity, with increased muscle glucose uptake without changes in muscle TG content. In liver, fasting resulted in increased mRNA expression of genes promoting gluconeogenesis and TG synthesis but in decreased mRNA expression of genes involved in glycogenolysis and fatty acid synthesis. In muscle, increased mRNA expression of genes promoting glucose uptake, as well as lipogenesis and beta-oxidation, was found. In conclusion, 16 h of fasting does not induce hepatic insulin resistance, although it causes liver steatosis, whereas muscle insulin sensitivity increases without changes in muscle TG content. Therefore, fasting induces differential changes in tissue-specific insulin sensitivity, and liver and muscle TG contents are unlikely to be involved in these changes.

Highlights

There is a lot of evidence on the action of fatty acid derivatives as agonists and antagonists for nuclear transcription factors, such as peroxisome proliferator-activated receptors (PPARs) and sterol-regulatory element binding proteins (SREBPs) [7, 8]
On hepatic and muscle insulin sensitivity in wild-type mice in vivo in relation to 1) tissue TG accumulation and 2) changes in mRNA expression of transcription factors and related proteins involved in glucose and lipid metabolism
This study indicates that fasting does not result in changes in hepatic insulin sensitivity with regard to Hepatic glucose production (HGP) in vivo

Summary

Introduction

There is a lot of evidence on the action of fatty acid derivatives as agonists and antagonists for nuclear transcription factors, such as peroxisome proliferator-activated receptors (PPARs) and sterol-regulatory element binding proteins (SREBPs) [7, 8] These transcription factors profoundly alter the expression of enzymes/proteins involved in glucose and lipid metabolism [8,9,10,11,12,13] and have interactions with hormones such as insulin [14, 15]. On hepatic and muscle insulin sensitivity in wild-type mice in vivo in relation to 1) tissue TG accumulation and 2) changes in mRNA expression of transcription factors and related proteins involved in glucose and lipid metabolism

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Conclusion