Long-Term Intake of a High-Protein Diet Affects Body Phenotype, Metabolism, and Plasma Hormones in Mice

Abstract

High-protein diets (HPDs) recently have been used to obtain body weight and fat mass loss and expand muscle mass. Several studies have documented that HPDs reduce appetite and food intake. Our goal was to determine the long-term effects of an HPD on body weight, energy intake and expenditure, and metabolic hormones. Male C57BL/6 mice (8 wk old) were fed either an HPD (60% of energy as protein) or a control diet (CD; 20% of energy as protein) for 12 wk. Body composition and food intakes were determined, and plasma hormone concentrations were measured in mice after being fed and after overnight feed deprivation at several time points. HPD mice had significantly lower body weight (in means ± SEMs; 25.73 ± 1.49 compared with 32.5 ± 1.31 g; = 0.003) and fat mass (9.55% ± 1.24% compared with 15.78% ± 2.07%; = 0.05) during the first 6 wk compared with CD mice, and higher lean mass throughout the study starting at week 2 (85.45% ± 2.25% compared with 75.29% ± 1.90%; = 0.0001). Energy intake, total energy expenditure, and respiratory quotient were significantly lower in HPD compared with CD mice as shown by cumulative energy intake and eating rate. Water vapor was significantly higher in HPD mice during both dark and light phases. In HPD mice, concentrations of leptin [feed-deprived: 41.31 ± 11.60 compared with 3041 ± 683 pg/mL ( = 0.0004); postprandial: 112.5 ± 102.0 compared with 8273 ± 1415 pg/mL ( < 0.0001)] and glucagon-like peptide 1 (GLP-1) [feed-deprived: 5.664 ± 1.44 compared with 21.31 ± 1.26 pg/mL ( = <0.0001); postprandial: 6.54 ± 2.13 compared with 50.62 ± 11.93 pg/mL ( = 0.0037)] were significantly lower, whereas postprandial glucagon concentrations were higher than in CD-fed mice. In male mice, the 12-wk HPD resulted in short-term body weight and fat mass loss, but throughout the study preserved body lean mass and significantly reduced energy intake and expenditure as well as leptin and GLP-1 concentrations while elevating postprandial glucagon concentrations. This study suggests that long-term use of HPDs may be an effective strategy to decrease energy intake and expenditure and to maintain body lean mass.

Long-term high-protein diet intake reverts weight gain and attenuates metabolic dysfunction on high-sucrose-fed adult rats

“…Noteworthy, our HPD-fed rats did not regain body weight, as did in other studies with identical nutritional intervention period [ 17 , 20 , 52 , 53 ]. This finding may be related to the fact that our HPD contained nearly 35% of energy as protein, whereas those used in the aforementioned studies had a minimum of 48%.…”

“…In accordance, HS/HP rats had the lowest energy intake among all groups, which was assessed throughout the nutritional intervention. Previous studies in rodents have confirmed the capacity of diets containing up to 60% of energy as protein to reduce energy intake and body weight [ 17 , 21 , 49 ]. In both rats [ 19 ] and mice [ 17 ], high-protein effects on satiety have been ascribed to the action of gastrointestinal peptides, such as cholecystokinin and glucagon-like peptide 1, on the nucleus of solitary tract, while the possible role of HPD low palatability has been ruled out by different studies [ 17 , 19 , 50 , 51 ].…”

“…Much of the approaches have prioritized low-fat and/or low-carbohydrate interventions [ 13 ]. On the other hand, current studies have suggested high-protein diets to promote greater weight-loss and metabolic outcomes in both human beings [ 14 , 15 ] and rodents [ 16 , 17 ]. The main rationale behind such advantage is that dietary proteins induce the release of anorexigenic and orexigenic hormones, which ultimately modulate neuronal pathways involved in the regulation of appetite and satiety, as well as energy expenditure [ 17 – 19 ].…”

“…On the other hand, current studies have suggested high-protein diets to promote greater weight-loss and metabolic outcomes in both human beings [ 14 , 15 ] and rodents [ 16 , 17 ]. The main rationale behind such advantage is that dietary proteins induce the release of anorexigenic and orexigenic hormones, which ultimately modulate neuronal pathways involved in the regulation of appetite and satiety, as well as energy expenditure [ 17 – 19 ]. Contrariwise, some studies have shown high-protein intake effects are only temporary and subjects (human beings and rodents) regain body weight upon mid- to long-term interventions, suggesting a metabolic adaptation to high-protein regimens [ 20 – 22 ].…”

Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons

“…Last, we asked whether this newly characterized circuit was relevant not only for the feeding-suppressive effect of NTS leucine, but also for the anorectic response to high-protein feeding. In mice, acute exposure to a high protein diet reduces appetite and weight gain (Vu et al, 2017). While the central mechanisms mediating these responses are poorly characterized, the NTS is established a neuroanatomical site responding to high protein diets (Darcel et al, 2005).…”