Abstract

To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.

Highlights

  • To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of Fibroblast Growth Factor 21 (FGF21) in the adaptation to a low protein diet

  • Fat mass was low in P3 and P5-fed rats, but when fat mass was expressed relative to body weight, only the P8 group differed significantly from the P3 group

  • In order to investigate whether the increase of plasma FGF21 was related to energy expenditure markers, the present study investigated the expression of genes involved in energy oxidation and browning of white adipose tissue, in brown and white adipose tissue

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Summary

Introduction

In young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. FGF21 responds to different nutritional deficiencies, such as those caused by low protein diets as well as amino acid and choline-deficient ­diets[18,19,20,21] All of these diets have been observed to increase circulating FGF21 levels and hepatic expression of Fgf[21] in mice and ­rats[11,15,18,22,23,24]. The effects of a low protein diet on food intake, energy expenditure and body weight involve FGF21. No study has investigated the impact of different levels of protein deficiency on the relative hepatic and systemic expression and variation of FGF21 and on hypothalamic expression

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