Low-protein and methionine, high-starch diets increase energy intake and expenditure, increase FGF21, decrease IGF-1, and have little effect on adiposity in mice

Abstract

Low-protein diets most often induce increased energy intake in an attempt to increase protein intake to meet protein needs with a risk of accumulation as fat of the excess energy intake. In female adult BALB/c 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. The effect on fat mass was however limited because total energy expenditure increased to the same extent as energy intake. Lean body mass was preserved in all 6% fed mice and reduced only in 3% casein-fed animals. 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 uncoupling protein 1 and increased fibroblast growth factor 21 (FGF21) in brown adipose tissue and increased FGF21, fatty acid synthase, and cluster of differentiation 36 in the liver. In the hypothalamus, neuropeptide Y was increased and proopiomelanocortin was decreased only in 3% casein-fed mice. In plasma, when protein was decreased, insulin-like growth factor-1 decreased and 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. In 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.

Sexually Dimorphic Effects of Dietary Methionine Restriction are Dependent on Age when the Diet is Introduced

“…And although BAT Ucp1 mRNA was not increased by the low-protein diet in this study, energy intake and EE were both increased by the low-protein diet (40). The common feature of both studies is that female mice responded to the low-protein diet by preserving their fat mass at the expense of lean tissue, and when the diet produced weight loss, lean tissue was the affected tissue component (15,40). In contrast, male mice preserved lean mass on the low-protein diet and lost fat mass (15).…”

“…The sex‐specific differences in response to the low‐protein diet were attributed in part to a blunting of the diet‐induced increase in plasma FGF21 in females and a lack of induction of BAT and IWAT Ucp1 mRNA by the low‐protein diet . Chaumontet et al conducted a slightly longer protein restriction study with younger female BALB/c mice and found that fat mass was unchanged after 8 weeks of the low‐protein diet, whereas lean mass was significantly decreased, accounting for essentially all of the BW loss over this period. And although BAT Ucp1 mRNA was not increased by the low‐protein diet in this study, energy intake and EE were both increased by the low‐protein diet .…”

“…Chaumontet et al conducted a slightly longer protein restriction study with younger female BALB/c mice and found that fat mass was unchanged after 8 weeks of the low‐protein diet, whereas lean mass was significantly decreased, accounting for essentially all of the BW loss over this period. And although BAT Ucp1 mRNA was not increased by the low‐protein diet in this study, energy intake and EE were both increased by the low‐protein diet . The common feature of both studies is that female mice responded to the low‐protein diet by preserving their fat mass at the expense of lean tissue, and when the diet produced weight loss, lean tissue was the affected tissue component .…”

“…In the studies conducted herein, we looked for sex‐specific differences in the responses of young, growing mice and adult, weight‐stable mice to 8 weeks of dietary MR. We examined variables associated with energy balance, nutrient partitioning to lean and fat deposition, and the well‐documented endocrine and transcriptional responses in liver, BAT, and IWAT. An initial objective was to establish whether the reported unresponsiveness of young, growing female mice to protein dilution would be replicated with dietary MR. We observed two fundamental differences in the way young female mice responded to MR compared with age‐matched males. First, female mice on the MR diet deposited less lean tissue than mice on the Con diet, whereas fat deposition in the two groups of mice did not differ.…”

The influences of low protein diet on the intestinal microbiota of mice

“…Other researchers have investigated food intake in low-protein diets, but they provided inconsistent results. Our results on food consumption corresponded with the findings of www.nature.com/scientificreports/ Larson et al 12 , but are contrary to the other research in which an increase in food consumption was reported 13,14 . Inconsistent results across numerous studies are difficult to fully explain, but may reflect differences in age, sex and breed.…”