Low protein/low methionine/high carbohydrate diets induce hyperphagia, increase energy expenditure and FGF21, but modestly affect adiposity infemale BalbC mice.

ObjectivesLow-protein diets are reported to induce hyperphagia in an effort to fulfil protein needs but at the expense of energy balance with a risk to gain in adiposity. However, different studies conducted on low-protein diets in animal and human did not confirm weight and body fat gain because an increased energy expenditure compensated more or less completely for the increase in energy intake and prevents the gain in adiposity. Thepresent study evaluated in mice the consequence of protein restricted diets combined with protein quality (milk protein versus soy protein with slight methionine deficiency) on energy intake, energy expenditure and adiposity and the role of FGF21 in the response to these protein restricted dietsMethodsThe present study investigated in female BalbC mice the behavioral, metabolic and phenotypic responses to 8 weeks feeding a very low (3%), moderately low (6%) or adequate (20%) dietary protein content and whether methionine scarcity in the dietary protein (Soy protein vs casein) affected these responses. Food intake, body weigh, adiposity (assessed by DEXA), were measured throughout the study and body composition determined by dissection at the end of the study. Plasma, liver, muscle, adipose tissue and hypothalamus samples were collected for nutrient, hormones and/or gene expression measurements.The different mice groups : P20C 20% casein, P20S 20% soy protein, P6C 6% casein, P6S 6% soy protein, P6S-Cor 6% soy protein corrected for methionine, P3C 3% casein ResultsIn female adult BalbC mice, a decrease in dietary casein from 20% to 6% and 3% increased energy intake and slightly increased adiposity, and this response was exacerbated with soy proteins with low methionine content compared to milk protein (figure 1). Lean body mass was reduced in 3% casein fed mice but preserved in all 6% fed mice. The effect on fat mass was however limited because total energy expenditure (TEE) increased to the same extent as energy intake (figure 2). In plasma, when protein was decreased, IGF-1 decreased, FGF21 increased and plasma FGF21 was best described by using a combination of dietary protein level, protein to carbohydrate ratio and protein to methionine ratio in the diet (figure 3). Insulin response to an oral glucose tolerance test was reduced in soy fed mice and in low-protein fed mice. Low-protein diets did not affect Ucp1 but increased Fgf21 in brown adipose tissue and increased Fgf21, Fas, and Cd36 in the liver. In the hypothalamus, Npy wasincreased and Pomc was decreased only in 3% casein fed mice.ConclusionsIn conclusion, reducing dietary protein and protein quality increases energy intake but also energy expenditure resulting in an only slight increase in adiposity. In this process FGF21 is probably an important signal that responds to a complex combination of protein restriction, protein quality and carbohydrate content of the diet.