0476 Low protein diets produce divergent effects on energy balance

The protein leverage theory postulates that diets low in dietary protein increase total energy intake due to overconsumption of carbohydrates and fat in an attempt to meet protein requirements. However, little is known of the mechanisms by which protein deficiency elicits such behavioral and metabolic adaptations, promotes positive energy balance and increases the risks for obesity and associated metabolic disorders. Our objectives were to determine the effects of graded degrees of protein restriction on (1) energy balance, body composition, glucose tolerance, gut hormones, (2) sympathetic signaling and, (3) key regulatory markers of thermogenesis in liver, skeletal muscle and brown adipose in diet-induced obese (DIO) rats. The DIO rats were randomized to receive one of 4 isocaloric high-fat diets with graded concentrations of protein (n = 8/group; 4.40 kcal/g): Control (15% protein, CON), 10% (10P), 5% (5P), 0% (0P) for 2 wk, followed by realimentation to CON for 2 wk. Food intake, energy expenditure, body composition, glucose tolerance, plasma hormone concentrations, and tissue gene and protein expressions were measured. Data were analyzed by linear mixed models or ANOVA. We found that during protein restriction, compared with CON, 0P decreased energy intake but increased energy expenditure which led to reduced body weight, fat and lean mass, 5P increased energy intake and energy expenditure which led to reduced body weight and lean mass, and 10P increased energy intake but did not affect body weight and composition. These diet-induced alterations in energy expenditure are in part mediated through enhanced β-adrenergic signaling coupled with upregulation of key thermogenic markers (UCP1, β-Adrenergic receptors, fibroblast growth factor-21, irisin) in the brown adipose, liver and skeletal muscle. The 0P decreased plasma peptide YY, leptin, insulin, C-peptide and tended to decrease amylin and glucose-dependent insulinotropic peptide. The 0P and 5P induced fatty liver, reduced energy digestibility, and decreased lean mass and body weight that persisted beyond the restriction period. In contrast, moderately low protein diets promoted gain in body weight and adiposity following the period of protein restriction. In summary, our novel findings demonstrate that low protein diets produce divergent effects on energy balance by engaging sympathetic signaling. Importantly, moderately low protein diets could exacerbate preexisting susceptibility to weight gain and obesity. Funding: NSERC, ALMA

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