Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure

Abstract

Low protein diets are associated with increased lifespan and improved cardiometabolic health primarily in rodents, and likely improve human health. There is strong evidence that moderate to severe reduction in dietary protein content markedly influences caloric intake and energy expenditure, which is often followed by a decrease in body weight and adiposity in animal models. While the neuroendocrine signals that trigger hyperphagic responses to protein restriction are better understood, there is accumulating evidence that increased sympathetic flux to brown adipose tissue, fibroblast growth factor-21 and serotonergic signaling are important for the thermogenic effects of low protein diets. This mini-review specifically focuses on the effect of low protein diets with variable carbohydrate and lipid content on energy intake and expenditure, and the underlying mechanisms of actions by these diets. Understanding the mechanisms by which protein restriction influences energy balance may unveil novel approaches for treating metabolic disorders in humans and improve production efficiency in domestic animals.

Keywords: energy balance; energy expenditure; food intake; low protein; neuroendocrine.

Figure 1

Potential mechanisms by which protein dilution alters energy intake and energy expenditure. Protein restriction concurrently increases energy intake and energy expenditure. Amino acids insufficiency is sensed by liver, small intestine, and brain by the involvement of unchanged tRNA, non-derepressible (GCN2), eukaryotic translation initiation factorα (eIF2α) and activating transcription factor 4 (ATF4) which results in hyperphagia to restore protein balance. The low protein induced hyperphagia is possibly mediated by increased circulating concentrations of ghrelin and fibroblast growth factor-21 (FGF21), and neuropeptide Y (NPY) expression in the hypothalamus. Whether reduced secretion of anorexigenic gut peptides such as peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) contribute to increased energy intake following protein dilution is not completely known. The increased energy expenditure in response to protein restriction is mediated by multiple mechanisms including increased sympathetic flux and upregulation of thermogenic markers in brown adipose tissue (BAT), and muscle thermogenesis. Whether local FGF21 secreted by skeletal muscle, small intestine and BAT, and 5-hydroxytryptamine (5HT) signaling in BAT play a role in low protein induced thermogenesis via autocrine, paracrine and endocrine pathways remains unclear. B-AR, beta adrenergic receptors; UCP1, uncoupling protein-1; PGC-1α, proliferator-activated receptor gamma coactivator 1-alpha; TPH1, tryptophan hydroxylase 1; SERT, serotonin transporter.