Objective: The objective was to assess effects of IF on intermediary metabolism and energy expenditure.

Design: Glucose, glycerol, and valine fluxes were measured after 2 wk of IF and a standard diet (SD) in 8 lean healthy volunteers in a crossover design, in the basal state and during a 2-step hyperinsulinemic euglycemic clamp, with assessment of energy expenditure and phosphorylation of muscle protein kinase B (AKT), glycogen synthase kinase (GSK), and mammalian target of rapamycine (mTOR). We hypothesized that IF selectively increases peripheral glucose uptake and lowers proteolysis, thereby protecting protein stores.

Results: No differences in body weight were observed between the IF and SD groups. Peripheral glucose uptake and hepatic insulin sensitivity during the clamp did not significantly differ between the IF and SD groups. Likewise, lipolysis and proteolysis were not different between the IF and SD groups. IF decreased resting energy expenditure. IF had no effect on the phosphorylation of AKT but significantly increased the phosphorylation of glycogen synthase kinase. Phosphorylation of mTOR was significantly lower after IF than after the SD.

Conclusions: IF does not affect whole-body glucose, lipid, or protein metabolism in healthy lean men despite changes in muscle phosphorylation of GSK and mTOR. The decrease in resting energy expenditure after IF indicates the possibility of an increase in weight during IF when caloric intake is not adjusted. This study was registered at www.trialregister.nl as NTR1841.

Objective: We hypothesized that a decrease in REE adjusted for FFM with weight loss would be partly explained by a disproportionate loss in the high metabolic activity component of FFM.

Design: Forty-five overweight and obese women [body mass index (in kg/m²): 28.7–46.8] aged 22–46 y followed a low-calorie diet for 12.7 ± 2.2 wk. Body composition was measured by magnetic resonance imaging, dual-energy X-ray absorptiometry, and a 4-compartment model. REE measured by indirect calorimetry (REEm) was compared with REE calculated from detailed body-composition analysis (REEc) by using specific organ metabolic rates (ie, organ REE/mass).

Results: Weight loss was 9.5 ± 3.4 kg (8.0 ± 2.9 kg FM and 1.5 ± 3.1 kg FFM). Decreases in REE (–8%), free triiodothyronine concentrations (–8%), muscle (–3%), heart (–5%), liver (–4%), and kidney mass (–6%) were observed (all P < 0.05). Relative loss in organ mass was significantly higher (P < 0.01) than was the change in low metabolically active FFM components (muscle, bone, and residual mass). After weight loss, REEm – REEc decreased from 0.24 ± 0.58 to 0.01 ± 0.44 MJ/d (P = 0.01) and correlated with the decrease in free triiodothyronine concentrations (r = 0.33, P < 0.05). Women with high adaptive thermogenesis (defined as REEm – REEc < –0.17 MJ/d) had less weight loss and conserved FFM, liver, and kidney mass.

Conclusions: After weight loss, almost 50% of the decrease in REEm was explained by losses in FFM and FM. The variability in REEm explained by body composition increased to 60% by also considering the weight of individual organs.

Objective: The aim was to assess the effect of high protein intake on high-fat diet–induced IHCL accumulation and insulin sensitivity in healthy young men.

Design: Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by ¹H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography–mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens.

Results: The HF diet increased IHCLs by 90 ± 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 ± 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 ± 11% and β-hydroxybutyrate by 61 ± 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma β-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 ± 24% after the HFHP diet (P = 0.14).

Conclusions: Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.

Objective: We aimed to compare the postprandial regional utilization of proteins with similar AA profiles but different absorption kinetics by coupling clinical experiments with compartmental modeling.

Design: Experimental data pertaining to the intestine, blood, and urine for dietary nitrogen kinetics after a ¹⁵N-labeled intact (IC) or hydrolyzed (HC) casein meal were obtained in parallel groups of healthy adults (n = 21) and were analyzed by using a 13-compartment model to predict the cascade of dietary nitrogen absorption and regional metabolism.

Results: IC and HC elicited a similar whole-body postprandial retention of dietary nitrogen, but HC was associated with a faster rate of absorption than was IC, resulting in earlier and stronger hyperaminoacidemia and hyperinsulinemia. An enhancement of both catabolic (26%) and anabolic (37%) utilization of dietary nitrogen occurred in the splanchnic bed at the expense of its further peripheral availability, which reached 18% and 11% of ingested nitrogen 8 h after the IC and HC meals, respectively.

Conclusions: The form of delivery of dietary AAs constituted an independent factor of modulation of their postprandial regional metabolism, with a fast supply favoring the splanchnic dietary nitrogen uptake over its peripheral anabolic use. These results question a possible effect of ingestion of protein hydrolysates on tissue nitrogen metabolism and accretion. This trial was registered at clinicaltrials.gov as NCTNCT00873951.

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/m²) 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, and EE was measured in a respiration chamber. Endogenous glucose production (EGP) and fractional gluconeogenesis were measured via infusion of [6,6-²H₂]glucose and ingestion of ²H₂O; 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 (EE = 0.007 x gluconeogenesis – 0.038; r = 0.70, R² = 0.49, P < 0.05). The contribution of gluconeogenesis to EE 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.