Dietary protein restriction promotes leanness while enabling strength gain in mice

Abstract

Background: Obesity, metabolic syndrome, and type 2 diabetes have dramatically grown in prevalence over the last decade. Weight loss and lifestyle modifications are often prescribed, as adherence to a resistance exercise training program reduces adiposity and improves glucose sensitivity. Despite the popularity of high protein diets for weight loss and muscle building, prospective and retrospective population-based studies as well as randomized clinical trials have shown that reduced protein intake is associated with better metabolic health in humans, the majority of whom are sedentary. Similar results are observed in sedentary rodents, where reduced protein intake improves metabolic health and body composition. We hypothesized that a unifying explanation of these results is that exercise is protective against high dietary protein intake. Here, we investigate how dietary protein intake interacts with resistance exercise training in mice to determine outcomes related to metabolic health. Methods: Male mice were assigned a group with either a high (36%) or low (7%) protein diet with or without a previously validated 12-week progressive overload resistance training program. Food consumption, body composition, and fitness were measured along with metabolic phenotyping outcomes. Results: Similar to previous studies, the low protein diets improved body composition in male mice when compared to high protein. However, high protein-fed sedentary animals accumulated significantly more fat mass than high protein-fed exercising mice. Low protein consumption significantly improves blood sugar control compared to high protein diets independently of resistance exercise, though resistance exercise itself may also promote glucose tolerance. Increasing dietary protein intake leads to more rapid strength and lean muscle gain in response to resistance exercise training. However, exercising low protein-fed mice eventually gained similar strength to high protein-fed exercised mice. Conclusions: Our results suggest that while low protein diets maximize metabolic health for sedentary mice, resistance exercise and muscle growth may be protective against some, but not all, negative metabolic effects of high protein diets and lead to greater strength and muscle mass. Future studies will be needed to determine if resistance or other forms of exercise are protective against the negative metabolic effects of high protein diets in humans, and to examine if resistance exercise allows high-protein-fed animals to live long, healthy lifespans.