Regulation of fatty acid oxidation in chicken (Gallus gallus): Interactions between genotype and diet composition

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Abstract

To explore the mechanisms leading to excessive adiposity in chicken, we investigated the regulation of fatty acid oxidation depending on genotype-related body fatness and diet composition. mRNA expression and/or activity of proteins involved in mitochondrial energy metabolism were measured in liver and gastrocnemius muscle of genetically lean or fat chickens reared on a low-fat/high-protein diet or an isoenergetic high-fat/low-protein diet (HF/LP). Muscle expressions of the muscle isoform of carnitine-palmitoyltransferase 1 (M-CPT1) and PPARβ/δ were higher in fat than in lean chickens. This was also observed in liver, although only with the HF/LP diet for M-CPT1. This could stimulate mitochondrial fatty acid oxidation in fat chickens. Up-regulations of liver and muscle CPT-1 hepatic isoform, and muscle cytochrome-c-oxidase mRNA expressions, and of β-hydroxyacyl-CoA-dehydrogenase activities suggest higher fatty acid utilization with the HF/LP diet. PPARβ/δ and PGC-1α could control fatty acid oxidation in muscle and liver, respectively. Regulation of avian uncoupling protein (avUCP) mRNA was tissue-dependent. Predominantly expressed in muscle, it was stimulated in fat and in HF/LP-fed chickens, where it could be associated to the special need in muscle anti-oxidant pathways of fatter animals. In liver it was lower in fat than in lean chickens, and its potential function remains to be clarified.

Introduction

The utilization of fatty acids as energy substrate may be of importance in tissues such as liver and oxidative or mixed type skeletal muscles, especially in case of cold exposure, fasting or exercise. In mammals, mitochondrial β-oxidation is quantitatively the main mechanism providing energy from fatty acids in cells. Long chain fatty acids are imported into the mitochondrial matrix by the carnitine–palmitoyltransferase (CPT) system (Bartlett and Eaton, 2004), where the transfer of acyl groups from coenzyme A to carnitine is controlled by the enzyme CPT1. Up to now, one liver and one muscle CPT1 isoforms have been evidenced in chicken (Skiba-Cassy et al., 2007), as is the case in humans (Britton et al., 1997). After this step, fatty acids are oxidized by the β-oxidation pathway, in which the β-hydroxyacyl CoA dehydrogenase (HAD) is considered as the rate-limiting enzyme in mammals (McGarry et al., 1989, Eaton, 2002). The provided acetyl-CoA enters the tricarboxylic acid (TCA) cycle, resulting in the reduction of co-factors. These cofactors are re-oxidized at the level of the mitochondrial respiratory chain, in which cytochrome c oxidase (COx) is the key-enzyme regulating O2 consumption. The efficiency of the resulting ATP synthesis might be modulated by a mild uncoupling. Part of this uncoupling could be controlled by uncoupling proteins UCP (i.e. avian avUCP in birds; Raimbault et al., 2001). The avUCP gene has been shown to be mainly expressed in skeletal muscles (Evock-Clover et al., 2002), and recently reported to be the avian ortholog to the mammalian UCP3 (Emre et al., 2007, Saito et al., 2008). This protein has been suggested to be involved in heat production in chicken, duckling and king penguin (Raimbault et al., 2001, Taouis et al., 2002, Toyomizu et al., 2002, Collin et al., 2003a, Collin et al., 2003c, Collin et al., 2005, Collin et al., 2007, Rey et al., 2008), in fatty acid or metabolic anion transport (Collin et al., 2003b, Mozo et al., 2005) and more recently in the limitation of reactive oxygen species (ROS) generation in avian species (Criscuolo et al., 2005), including king penguins (Talbot et al., 2003) and chickens (Abe et al., 2006, Mujahid et al., 2006).

Fast growing chickens (Gallus gallus) develop excessive adiposity besides the high muscle mass resulting from selection. Most attention has been paid to the control of lipogenesis in this species (Daval et al., 2000, Bourneuf et al., 2006). However, information is scarce about the mechanisms regulating lipolysis and energy expenditure, especially mitochondrial fatty acid utilization. In humans, a reduction in the rate of muscle lipid oxidation has been postulated to favor peripheral fat accumulation (Colberg et al., 1995, Marques-Lopes et al., 2001, Young et al., 2002), one candidate mechanism being a reduction in the activity of CPT 1 (Alam and Saggerson, 1998, Kim et al., 2000, Chan et al., 2005). In addition, rainbow trout selected for muscle high fat content presents reduced hepatic fatty acid oxidation and mitochondrial oxidative capacities in both liver and muscle when compared to their lean counterparts (Kolditz et al., 2008).

In order to better understand these mechanisms in chickens, effects of genotype and diet composition on the regulation of mitochondrial fatty acid utilization and of O2 consumption were investigated in two major tissues for fatty acid oxidation, liver and muscle. This study is the second part of an experiment (Swennen et al., 2006) substituting energy and proteins in two isoenergetic diets offered to two genetically divergent lines of broiler chickens selected on their abdominal fat content (Leclercq et al., 1980). These diets affected growth and abdominal fat content of both lines, without influencing significantly heat production or diet-induced thermogenesis (Swennen et al., 2006). In the present article, we give further insight into the control of mitochondrial fatty acid utilization, by measuring the expression or activity of several genes involved in these mechanisms in liver and skeletal muscle. In addition, we focus on the expression of the avian uncoupling protein that could play a major role in the regulation of energy metabolism (thermogenesis, prevention of oxidative stress or lipotoxicity) of avian species.

Section snippets

Experimental design

Sixty day-old male broiler chickens (Gallus gallus) of genetically fat and lean lines (INRA Nouzilly, France; Leclercq et al., 1980) were reared in the conditions described by Swennen et al. (2006).

Briefly, from 14 days of age, chickens of each line were divided into two groups, each receiving one of two isoenergetic diets (Table 1), resulting in a total of 4 groups of 15 chickens. The isoenergetic diets contained the same ingredients included in different proportions. The concentrations of

Regulation of hepatic mitochondrial metabolism

We first investigated mRNA expressions of genes involved in long-chain fatty acid transfers through the mitochondrial membrane and fatty acid utilisation in hepatic mitochondria (Fig. 1A to D).

In liver, L-CPT1 mRNA expression was 1.5 to 2-fold higher in chickens fed with the HF/LP diet compared to chickens fed with the LF/HP diet (P < 0.01; Fig. 1A). Messenger RNA expression of the muscle predominant CPT1, M-CPT1, was also regulated by the composition of the diet with a significant interaction

Experimental model

Genetically fat and lean lines of broiler chicken were developed by Leclercq et al. (1980) in order to investigate the mechanisms controlling fattening in this species. These lines differ in carcass lipid and muscle glycogen content, but exhibit similar live body weight, feed consumption and energy expenditure (Geraert et al., 1988, Sibut et al., 2008). Moreover, in the present experiment, abdominal fat content of chickens from the fat line was more affected by changes in diet composition:

Acknowledgements

The authors gratefully thank N. Millet, A. Boucard, C. Jenkins and E Godet for their technical assistance, E. Baeza, and J. Simon for helpful discussions (INRA, France), as well as G.P.J. Janssens and I. Vaesen (Belgium) for the experimental design. This work was partly supported by the Research Fund Katholieke Universiteit Leuven (OT/02/36) and INRA. R. Joubert is a PhD student supported by a grant from INRA and Région Centre, France and Quirine Swennen is supported by the Research Foundation

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