Impaired Skeletal Muscle Branched-Chain Amino Acids Catabolism Contributes to Their Increased Circulating Levels in a Non-Obese Insulin-Resistant Fructose-Fed Rat Model.

Jérémie David,Sergio Polakof,Dominique Dardevet,Isabelle Savary-Auzeloux,Laurent Mosoni

doi:10.3390/nu11020355

Abstract

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat–fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat–fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism.

Highlights

The place of amino acids has been recently questioned in the metabolic dysfunctions and plasma metabolites alterations associated with insulin resistance (IR) occurrence [1]
In the present study we showed for the first time that chronic fructose consumption for 45 days resulted in increased fasting branched-chain amino acids (BCAA) levels
These increased BCAA levels were associated with the installation of a whole-body glucose intolerance and IR

Summary

Introduction

The place of amino acids (namely branched chain amino acids, BCAA) has been recently questioned in the metabolic dysfunctions and plasma metabolites alterations associated with insulin resistance (IR) occurrence [1]. Among the mechanisms involved in this phenotype, a decreased capacity of the whole body to catabolize BCAA has been recently investigated, and a particular reduction of the BCAA catabolic enzymes in the adipose tissue has been reported in both animal model and humans [5,6,7]. It is unclear whether increased BCAA results from altered adipose tissue metabolism associated with obesity or if it originally results from the IR development, which will lead to obesity and dysfunction of BCAA metabolism in the adipose cells [1,8].

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