Plasma FGF21 concentrations and spontaneous self-selection of protein suggest that 15% protein in the diet may not be enough for male adult rats.

Protein requirement has been determined at 10%-15% energy. Under dietary self-selection, rats ingest 25%-30% energy as protein and regulate FGF21 (a hormone signaling protein deficiency) to levels lower than those measured with a 15% protein (15P) diet. Our hypothesis is that if a 15P diet was indeed sufficient to ensure protein homeostasis, it is probably a too low protein level to ensure optimal energy homeostasis. Adult male Wistar rats were used in this study. The first objective was to determine the changes in food intake, body composition, and plasma FGF21, IGF-1, and PYY concentrations in rats fed 8P, 15P, 30P, 40P, or 50P diets. The second was to determine whether the FGF21 levels measured in the rats were related to spontaneous protein intake. Rats were fed a 15P diet and then allowed to choose between a protein diet and a protein-free diet. Food intake and body weight were measured throughout the experiments. Body composition was determined at different experimental stages. Plasma samples were collected to measure FGF21, IGF-1, and PYY concentrations. A 15P diet appears to result in higher growth than that observed with the 30P, 40P, and 50P diets. However, the 15P diet probably does not provide optimal progression of body composition owing to a tendency of 15P rats to fix more fat and energy in the body. The variable and higher concentrations of FGF21 in the 15P diet suggest a deficit in protein intake, but this does not appear to be a parameter reflecting the adequacy of protein intake relative to individual protein requirements.NEW & NOTEWORTHY Under dietary self-selection, rats choose to ingest 25%-30% of energy as protein, a value higher than the protein requirement (10%-15%). According to our results, this higher spontaneous intake reflects the fact that rats fed a 15% protein diet, compared with high-protein diets, tend to bind more fat and have higher concentrations of FGF21, a hormone signaling protein deficiency. A 15% protein diet appears to be sufficient for protein homeostasis but not for optimal energy homeostasis.

Protein-carbohydrate interaction effects on energy balance, FGF21, IGF-1, and hypothalamic gene expression in rats.

Amino acids are involved in energy homeostasis, just as are carbohydrates and lipids. Therefore, mechanisms controlling protein intake should operate independently and in combination with systems controlling overall energy intake to coordinate appropriate metabolic and behavioral responses. The objective of this study was to quantify the respective roles of dietary protein and carbohydrate levels on energy balance, plasma fibroblast growth factor 21 (FGF21) and insulin growth factor 1 (IGF-1) concentrations, and hypothalamic neurotransmitters (POMC, NPY, AgRP, and CART). In a simplified geometric framework, 7-wk-old male Wistar rats were fed 12 diets containing 3%-30% protein for 3 wk, in which carbohydrates accounted for 30%-75% of the carbohydrate and fat part of the diet. As a result of this study, most of the studied parameters (body composition, energy expenditure, plasma FGF21 and IGF-1 concentrations, and Pomc/Agrp ratio) responded mainly to the protein content and to a lesser extent to the carbohydrate content in the diet.NEW & NOTEWORTHY As mechanisms controlling protein intake can operate independently and in combination with those controlling energy intakes, we investigated the metabolic and behavioral effects of the protein-carbohydrate interaction. With a simplified geometric framework, we showed that body composition, energy balance, plasma FGF21 and IGF-1 concentrations, and hypothalamic Pomc/Agrp ratio were primarily responsive to protein content and, to a lesser extent, to carbohydrate content of the diet.

Rats Self-Select a Constant Protein-to-Carbohydrate Ratio Rather Than a Constant Protein-to-Energy Ratio and Have Low Plasma FGF21 Concentrations.

BACKGROUND: Under dietary self-selection (DSS), rats ingest 25-30% of energy as protein. This high level appears to be explained by metabolic benefits related to reduced carbohydrate dependence and associated pathologies. However, the mechanisms underlying these choices remain largely misunderstood. OBJECTIVES: The aim was to test the hypothesis that in a DSS model, rats select a protein-to-energy (PE) ratio to maintain the protein-to-carbohydrate (PC) ratio constant and that fibroblast growth factor 21 (FGF21) is involved in this response. METHODS: Adult male Wistar rats were used in 3 experiments. The first was to determine whether the PE ratio was influenced by changes in carbohydrate content. The second was to test whether the PE ratio was defended with a modified DSS model. The third was to determine whether the selected PE ratio was of metabolic interest compared with a standard 15% protein diet. Food intake, body weight, and energy expenditure were measured. After 3 wk, plasma was sampled and rats were killed to determine body composition and gene expression. Statistical analyses were mainly done by ANOVA tests and correlation tests. RESULTS: The selected PE ratio increased from 20% to 35% when the carbohydrate content of the protein-free diet increased from 30% to 75% (R2 = 0.56; P < 10-6). Consequently, the PC ratio was constant (70%) in all groups (P = 0.18). In self-selecting rats, plasma FGF21 concentrations were 3 times lower than in rats fed the 5% protein diet (P < 10-4) and similar to those in rats fed a 30% diet. CONCLUSIONS: This study showed that self-selecting rats established PE ratios larger than those considered sufficient to achieve optimal growth in adult rats (10-15%), and the ratios were highly dependent on carbohydrates, apparently with the aim of maintaining a constant and high PC ratio. This was associated with a minimization of plasma FGF21.

Consumption of Ultra-Processed Foods by Pesco-Vegetarians, Vegetarians, and Vegans: Associations with Duration and Age at Diet Initiation.

BACKGROUND: There is a growing availability of industrial plant-based meat and dairy substitutes that can be classified as ultra-processed foods (UPFs). Very little is known about the consumption of UPFs by vegetarians. OBJECTIVE: The aim of this cross-sectional study, from the NutriNet-Santé cohort, was to describe the contribution of UPFs to different vegetarian diets, in relation to the nutritional quality of their diet, and determinants of UPF consumption, including duration and age at vegetarian diet initiation. METHODS: The study population (n = 21,212) was divided into 4 groups: 19,812 meat eaters, 646 pesco-vegetarians, 500 vegetarians, and 254 vegans. Daily food intakes were collected using repeated 24-h dietary records. Vegetarian diets were described by the proportion of energy from UPFs and the nutritional quality of the diet using healthy and unhealthy plant-based diet indices (PDIs). In a subsample without meat eaters (n = 1,400), a multivariable linear regression model was performed to study the association between UPF consumption and its determinants. RESULTS: Higher avoidance of animal-based foods was associated with a higher consumption of UPFs (P < 0.001), with UPFs supplying 33.0%, 32.5%, 37.0%, and 39.5% of energy intakes for meat eaters, pesco-vegetarians, vegetarians, and vegans. The nutritional quality of diets was also associated with the level of animal-based foods avoidance (P < 0.001), with healthy PDIs at 53.5, 60.6, 61.3 and 67.9 for meat-eaters, pesco-vegetarians, vegetarians, and vegans. Short duration and young age at diet initiation were associated with an increased consumption of UPFs (ßage at initiation = -0.003, P = 0.001; ßduration = -0.002, P < 0.001). CONCLUSIONS: Not all vegetarian diets necessarily have health benefits, because of potential adverse effects of UPFs on nutritional quality and healthiness of diet. UPF consumption by vegetarians and their diet characteristics should be considered in future studies on the links between vegetarianism and health. This trial was registered at clinicaltrials.gov as NCT03335644.

What does self-selection of dietary proteins in rats tell us about protein requirements and body weight control?

Omnivores are able to correctly select adequate amounts of macronutrients from natural foods as well as purified macronutrients. In the rat model, the selected protein levels are often well above the requirements estimated from the nitrogen balance. These high intake levels were initially interpreted as reflecting poor control of protein intake, but the selected levels were later found to be precisely controlled for changes in dietary protein quality and adjusted for cold, exercise, pregnancy, lactation, age, etc. and therefore met physiological requirements. Several authors have also suggested that instead of a given level of protein intake, rodents regulate a ratio of protein to dietary carbohydrates in order to achieve metabolic benefits such as reduced insulin levels, improved blood glucose control, and, in the long term, reduced weight and fat gain. The objective of this review was to analyze the most significant results of studies carried out on rats and mice since the beginning of the 20th century, to consider what these results can bring us to interpret the current causes of the obesity pandemic and to anticipate the possible consequences of policies aimed at reducing the contribution of animal proteins in the human diet.