High-Lard and High-Fish Oil Diets Differ in Their Effects on Insulin Resistance Development, Mitochondrial Morphology and Dynamic Behaviour in Rat Skeletal Muscle

Maria Pia Mollica,Lillà Lionetti,Rosalba Putti,Raffaella Sica

doi:10.4236/fns.2013.49a1017

Abstract

Fish oil (mainly omega 3 polyunsaturated fatty acids), differently from lard (mainly saturated fatty acids) has been suggested to have anti-inflammatory effects associated with amelioration of insulin sensibility. An important role in skeletal muscle insulin resistance development has been recently attributed to mitochondrial dynamic behavior. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes and a shift toward fission process has been associated with skeletal muscle mitochondrial dysfunction and insulin resistance development. The present work aimed to evaluate if the replacement of lard with fish oil in high-fat diet positively affect skeletal muscle mitochondrial dynamic behavior in association with the improvement of insulin-resistance. Body weight gain, systemic insulin-resistance (glucose/insulin ratio), serum TNFα levels and skeletal muscle lipid content were assessed in rats fed a high-lard or high-fish-oil diet for 6 weeks. In skeletal muscle sections, immunohistochemical analysis were performed to detect the presence of insulin receptor substrate 1 (IRS1) and tyrosine phosphorylated IRS1 (key factor in insulin signalling pathway) as well as to detect the main proteins involved in mitochondrial fusion (MFN2 and OPA1) and fission (DRP1 and Fis1) processes. Skeletal muscle mitochondrial ultrastructural features were assessed by electron microscopy. High-fish oil feeding induced lower body weight gain, systemic inflammation and insulin-resistance development as well as skeletal muscle lipid accumulation compared to high-lard feeding. Skeletal muscle sections from high-fish oil fed rats exhibited a greater number of immunoreactive fibers for MFN2 and OPA1 proteins as well as weaker immunostaining for DRP1 and Fis1 compared to sections from high-lard fed rats. Electron microscopy observations suggested a prominent presence of fission events in L rats and fusion events in F rats. The positive effect of the replacement of lard with fish oil in high-fat diet on systemic and skeletal muscle insulin sensibility was associated to changes in mitochondrial dynamic behavior.

Highlights

The debate on the roles played by different type of dietary fat in obesity development and associated diseases, such as insulin resistance, is still ongoing with controversies in finding on both positive and negative contribution of fatty acids to these diseases
The results showed that highlard feeding elicited mitochondrial fission morphotype with enhanced presence of fission proteins and reduced presence of Mfn2 in skeletal muscle associated with systemic insulin resistance and obesity development, whereas high-fish oil feeding evocated a prevalence of skeletal muscle mitochondrial fusion events associated with an higher systemic insulin sensibility and anti-obesity effects
The main aim of the present work was to evaluate whether high-lard and high-fish oil diets differently affect mitochondrial morphology and dynamic behavior in skeletal muscle associated with obesity and insulin-resistance development in experimental animal model

Summary

Introduction

The debate on the roles played by different type of dietary fat (saturated or unsaturated) in obesity development and associated diseases, such as insulin resistance, is still ongoing with controversies in finding on both positive and negative contribution of fatty acids to these diseases. Whether insulin resistance develops depends upon the type of dietary fat: the replacement of a small proportion of the diet with omega-3 fatty acids from fish oil completely prevents the development of skeletal muscle insulin resistance [4,5,6]. These beneficial effects have been linked with anti-inflammatory properties, but emerging data suggests that the mechanisms may converge on mitochondria, given that defects in mitochondrial performance has been suggested to contribute to the development of insulin resistance [7, FNS. Fission inhibition and/or fusion activation have been found to counteract many of the disease phenotypes related to IR and diabetes [17]

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