Effects of protein quantity and type on diet induced thermogenesis in overweight adults: A randomized controlled trial.

BACKGROUND & AIMS: Protein content of a meal is hypothesized to drive DIT dose-dependently. However, no single meal study exists comparing two different doses of protein on DIT. In addition, the source of protein, particularly whey protein, was shown to have a higher DIT than casein and soy in the acute setting, however the mechanism behind this difference is not yet clear. The aim of the present work is therefore to evaluate the efficacy of two different doses and types of protein (whey protein and casein) on DIT in overweight adults. METHODS: Randomized, double blind crossover including seventeen overweight men and women assigned to four isocaloric study treatments where protein and carbohydrate were exchanged: control, 30 g of whey protein microgels (WPM30), 50 g WPM (WPM50) or 50 g micellar casein (MC50). Energy expenditure was measured by indirect calorimetry. Blood, breath and urine samples were collected in order to measure substrate oxidation, amino acid profile, glucose and insulin, protein turnover and other metabolic parameters. RESULTS: DIT was 6.7 ± 3.7%, 13.0 ± 5.0%, 18.0 ± 5.0% and 16.0 ± 5.0% for control, WPM30, WPM50 and MC50, respectively. There was a significant difference between WPM50 and WPM30 (p < 0.005) and a trend was observed between WPM50 and MC50 (p = 0.06). WPM50 resulted in the highest total, essential, and branched-chain plasma amino acid concentrations when compared with the other study treatments (p < 0.005) and a higher insulin concentration than MC50 (p < 0.005). Protein oxidation was higher for WPM50 than MC50. Protein turnover was significantly correlated with DIT through total leucine oxidation (r = 0.52, p = 0.005). CONCLUSIONS: Our findings show that DIT does increase at a dose beyond 30 g of WPM and that the type of dairy protein may have an effect on DIT with WPM tending towards a higher DIT than casein. Although further research is required to understand the mechanism behind the effect of different protein sources on thermogenesis, we suggest that amongst the components of protein turnover, protein oxidation may be an important driver of thermogenesis at doses higher than 30 g. These results have concrete implications when choosing a dose of protein to optimize its thermogenic effect. CLINICAL TRIAL REGISTRY NUMBER: NCT02303080 www.clinicaltrials.gov.

A 48-Hour Vegan Diet Challenge in Healthy Women and Men Induces a BRANCH-Chain Amino Acid Related, Health Associated, Metabolic Signature.

SCOPE: Research is limited on diet challenges to improve health. A short-term, vegan protein diet regimen nutritionally balanced in macronutrient composition compared to an omnivorous diet is hypothesized to improve metabolic measurements of blood sugar regulation, blood lipids, and amino acid metabolism. METHODS AND RESULTS: This randomized, cross-over, controlled vegan versus animal diet challenge is conducted on 21 (11 female,10 male) healthy participants. Fasting plasma is measured during a 3 d diet intervention for clinical biochemistry and metabonomics. Intervention diet plans meet individual caloric needs. Meals are provided and supervised. Diet compliance is monitored. CONCLUSIONS: The vegan diet lowers triglycerides, insulin and homeostatic model assessment (HOMA-IR), bile acids, elevated magnesium levels, and changed branched-chain amino acids (BCAAs) metabolism (p < 0.05), potentiating insulin and blood sugar control after 48 h. Cholesterol control improves significantly in the vegan versus omnivorous diets. Plasma amino acid and magnesium concentrations positively correlate with dietary amino acids. Polyunsaturated fatty acids and dietary fiber inversely correlate with insulin, HOMA-IR, and triglycerides. Nutritional biochemistries, BCAAs, insulin, and HOMA-IR are impacted by sexual dimorphism. A health-promoting, BCAA-associated metabolic signature is produced from a short-term, healthy, controlled, vegan diet challenge when compared with a healthy, controlled, omnivorous diet.

Protein choices targeting thermogenesis and metabolism.

BACKGROUND: Dietary proteins stimulate thermogenesis and satiety more than does carbohydrate or fat; however, less is known about the differences between protein sources. OBJECTIVE: The objective was to determine the differential effects of 3 proteins on energy metabolism, satiety, and glucose control. DESIGN: Energy metabolism, satiety, and glucose control were measured in 23 lean, healthy subjects on separate occasions, before and 5.5 h after consumption of 4 isocaloric test meals in a randomized, double-blind, crossover design. Three meals consisting of 50% protein (whey, casein, or soy), 40% carbohydrate, and 10% fat and a fourth meal consisting of 95.5% carbohydrate were compared with a glucose meal that provided the same glucose load as the protein meals. RESULTS: The thermic effect was greater after the whey (14.4 ± 0.5%) than after the casein (12.0 ± 0.6%; P = 0.002) and soy (11.6 ± 0.5%; P = 0.0001) meals and was greater after the whey, casein, and soy meals than after the high-carbohydrate meal (6.6 ± 0.5%; P < 0.0001). Cumulative fat oxidation tended to be greater after the whey meal (16.2 ± 1.1 g) than after the soy meal (13.7 ± 1.0 g; P = 0.097) and was greater after the whey and soy meals than after the high-carbohydrate meal (10.9 ± 0.9 g; P < 0.05). The glycemic response to glucose was attenuated 32% by the proteins (P < 0.001) at the expense of a greater insulin response after whey than after glucose (154%; P = 0.02), casein (143%; P = 0.07), and soy (151%; P = 0.03). Subjective appetite sensations indicated that casein and soy were more satiating than whey (P < 0.01), but whey was more "liked" compared with casein and soy (P = 0.025 and P = 0.09, respectively). CONCLUSION: The results suggest that different protein sources could be used to modulate metabolism and subsequently energy balance.

Interleukin-18 protein level is upregulated in adipose tissue of obese mice.

In this study, we investigated the regulation of Interleukin-18 (IL-18) and caspase-1 mRNA and protein levels in adipose and liver tissue of obese (ob/ob) mice compared with ob/+ mice. In ob/ob mice, which have a twofold higher IL-18 plasma level as compared with lean mice, IL-18 mRNA expression was significantly reduced by 1.6-fold in adipose tissue, whereas protein level was enhanced fourfold as compared with ob/+ mice. However, caspase-1 mRNA expression and activity were significantly enhanced in adipose tissue of ob/ob mice. Conversely, both IL-18 mRNA and protein levels were slightly enhanced, but caspase-1 activity was reduced in liver of ob/ob mice as compared with lean mice. In conclusion, we show that adipose and hepatic IL-18 protein expressions are increased in obese mice. However, in contrast to liver, the adipose IL-18 protein level appears to be upregulated through a post-transcriptional mechanism probably involving caspase-1.

Apomine, a novel hypocholesterolemic agent, accelerates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and stimulates low density lipoprotein receptor activity.

Apomine, a novel 1,1-bisphosphonate ester, has been shown to lower plasma cholesterol concentration in several species. Here we show that Apomine reduced the levels of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), the rate-limiting enzyme in the mevalonate pathway, both in rat liver and in cultured cells. Apomine resembles sterols such as 25-hydroxycholesterol in its ability to potently accelerate the rate of HMGR degradation by the ubiquitin-proteasome pathway, a process that depends on the transmembrane domain of the enzyme. The similarity between Apomine and sterols in promoting rapid HMGR degradation extends to its acute requirements for ongoing protein synthesis and mevalonate-derived non-sterol product(s) as a co-regulator. Yet, at suboptimal concentrations, sterols potentiated the effect of Apomine in stimulating HMGR degradation, indicating that these agents act via distinct modes. Furthermore, unlike sterols, Apomine inhibited the activity of acyl-CoA:cholesterol acyltransferase in intact cells but not in cell-free extracts. Apomine stimulated the cleavage of the precursor of sterol-regulatory element-binding protein-2 and increased the activity of low density lipoprotein receptor pathway. This Apomine-enhanced activation of sterol-regulatory element-binding protein-2 was prevented by sterols or mevalonate. Taken together, our results provide a molecular mechanism for the hypocholesterolemic activity of Apomine.