Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet.

Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet.

Veldhorst MA, Westerterp-Plantenga MS, Westerterp KR.

NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Human Biology, Maastricht University Medical Centre, Maastricht, Netherlands, and the Top Institute Food and Nutrition, Wageningen, Netherlands.

BACKGROUND: High-protein diets have been shown to increase energy expenditure (EE). Objective: The objective was to study whether a high-protein, carbohydrate-free diet (H diet) increases gluconeogenesis and whether this can explain the increase in EE. DESIGN: Ten healthy men with a mean (+/-SEM) body mass index (in kg/m(2)) of 23.0 +/- 0.8 and age of 23 +/- 1 y received an isoenergetic H diet (H condition; 30%, 0%, and 70% of energy from protein, carbohydrate, and fat, respectively) or a normal-protein diet (N condition; 12%, 55%, and 33% of energy from protein, carbohydrate, and fat, respectively) for 1.5 d according to a randomized crossover design, whereas EE was measured in a respiration chamber. Endogenous glucose production (EGP) and fractional gluconeogenesis were measured via infusion of [6,6-(2)H(2)]glucose and ingestion of (2)H(2)O; absolute gluconeogenesis was calculated by multiplying fractional gluconeogenesis by EGP. Body glycogen stores were lowered at the start of the intervention with an exhaustive glycogen-lowering exercise test. RESULTS: EGP was lower in the H condition than in the N condition (181 +/- 9 compared with 226 +/- 9 g/d; P < 0.001), whereas fractional gluconeogenesis was higher (0.95 +/- 0.04 compared with 0.64 +/- 0.03; P < 0.001) and absolute gluconeogenesis tended to be higher (171 +/- 10 compared with 145 +/- 10 g/d; P = 0.06) in the H condition than in the N condition. EE (resting metabolic rate) was greater in the H condition than in the N condition (8.46 +/- 0.23 compared with 8.12 +/- 0.31 MJ/d; P < 0.05). The increase in EE was a function of the increase in gluconeogenesis (DeltaEE = 0.007 x Deltagluconeogenesis - 0.038; r = 0.70, R(2) = 0.49, P < 0.05). The contribution of Deltagluconeogenesis to DeltaEE was 42%; the energy cost of gluconeogenesis was 33% (95% CI: 16%, 50%). CONCLUSIONS: Forty-two percent of the increase in energy expenditure after the H diet was explained by the increase in gluconeogenesis. The cost of gluconeogenesis was 33% of the energy content of the produced glucose.