Meta-analysis links dietary branched-chain amino acids to metabolic health in rodents

Background The role of dietary branched chain amino acids (BCAAs) and their effect on metabolic health is complex. How dietary BCAA levels and their interaction with background nutrition affect health is unclear. Here, we used meta-analysis and meta-regression, together with the nutritional modelling, to analyse the results of rodent studies that increased the level of dietary BCAAs and measured circulating levels, outcomes related to metabolic health, body mass and food intake. Results Across all studies, increasing dietary BCAAs resulted in increased levels of circulating BCAAs. These effects, however, were heavily moderated by background dietary levels whereby on high BCAA diets, further increases were not reflected in the blood. Impaired glucose tolerance was associated with elevated dietary BCAAs, with the greatest effect occurring with a simultaneous increase in total protein intake. Effects of dietary BCAAs on plasma glucose, insulin, or HOMA emerged only when dietary macronutrient background was considered. We found that elevated dietary BCAAs increases % body fat, with largest increases in adiposity occurring when BCAAs are increased on a high protein, low carbohydrate dietary background. Finally, we found that increased dietary BCAAs were associated with increased food intake when the background diet was low in BCAAs. Conclusion Our data highlights the interaction between BCAAs and background nutrition. We show that the effects of BCAAs on metabolic health cannot be studied in isolation but must be considered as part of complex mixture of dietary components.

Positive Interactions Between Lactic Acid Bacteria Could Be Mediated by Peptides Containing Branched-Chain Amino Acids

Lactic acid bacteria (LAB) are responsible for the sanitary, organoleptic, and health properties of most fermented products. Positive interactions between pairs of LAB strains, based on nitrogen dependencies, were previously demonstrated. In a chemically defined medium, using milk and lupin proteins as sole nitrogen source, two proteolytic strains were able to sustain the growth of non-proteolytic strains, but one did not. The objective of the present study was, thus, to determine which specific peptides were implicated in the positive interactions observed. Peptides produced and involved in the bacterial interactions were quantified using tandem mass spectrometry (LC-MS/MS). About 2,000 different oligopeptides ranging from 6 to more than 50 amino acids in length were identified during the time-course of the experiment. We performed a clustering approach to decipher the differences in peptide production during fermentation by the three proteolytic strains tested. We also performed sequence alignments on parental proteins and identified the cleavage site profiles of the three bacterial strains. Then, we characterized the peptides that were used by the non-proteolytic strains in monocultures. Hydrophobic and branched-chain amino acids within peptides were identified as essential in the interactions. Ultimately, better understanding how LAB can positively interact could be useful in multiple food-related fields, e.g., production of fermented food products with enhanced functional properties, or fermentation of new food matrices.

Differential Effect of Non-Purified and Semi-Purified Standard Diets on Kynurenine and Peripheral Metabolites in Male C57BL/6J Mice

The kynurenine (Kyn) pathway plays crucial roles in several inflammation-induced disorders such as depression. In this study, we measured Kyn and other related molecules in the blood plasma, brain, and urine of male C57BL/6J mice (B6) fed non-purified (MF) and semi-purified (AIN-93G and AIN-93M) standard rodent diets. Mice fed MF had increased plasma Kyn levels compared with those on AIN93-based diets, as well as decreased hippocampal Kyn levels compared with those fed AIN-93G. Previous studies showed that branched chain amino acids (BCAAs) suppress peripheral blood Kyn transportation to the brain, but plasma BCAA levels were not significantly different between the diet groups in our study. Urine metabolome analysis revealed that feed ingredients affected the excretion of many metabolites, and MF-fed mice had elevated excretion of kynurenic and quinolinic acids, pivotal metabolites in the Kyn pathway. Collectively, the level of critical metabolites in the Kyn pathway in the central and peripheral tissues was strongly affected by feed ingredients. Therefore, feed selection is a critical factor to ensure the reproducibility of experimental data in studies involving rodent models.

Sarcopenia in Hepatocellular Carcinoma: Pathogenesis and Management

Background: Sarcopenia is almost constantly observed in patients with cirrhosis and hepatocellular carcinoma. Summary: Chronic liver disease represents a unique pathophysiological scenario in which sarcopenia develops and all factors involved in the pathogenesis should be taken into account for an appropriate management of the disease. No properly designed intervention studies on this topic are available and, thus, no effective strategies have been developed for clinical practice. Apart from any targeted intervention, treatment and optimization of liver disease is crucial. Key Messages: In patients with cirrhosis and hepatocellular carcinoma, nutritional support to maintain and restore nutrition status, a targeted use of branched-chain amino acids and a guided physical exercise, should all be an integral part of the multidimensional assessment and tailored interventions.

Association of dietary intake of branched-chain amino acids with long-term risks of cardiovascular disease, cancer and all-cause mortality

Objectives: Studies on associations between dietary intake of branched-chain amino acids (BCAAs) and long-term risks of cardiovascular disease (CVD), cancer, and all-cause mortality have yielded inconclusive results. This study aimed to investigate the associations between dietary BCAA intake and long-term risks of CVD, cancer, and all-cause mortality in nationwide survey participants aged ≥18. Design: This was a prospective cohort study of a nationally representative sample of 14,397 adults aged ≥18 who participated in the United States National Health and Nutrition Examination Survey III (NHANES III). Dietary intakes of BCAAs (leucine, isoleucine, and valine) were determined from the total nutrient intake document. The main outcomes were CVD, cancer, and all-cause mortality. Results: During 289,406 person-years of follow-up, we identified 4,219 deaths, including 1,133 from CVD and 926 from cancer. After multivariate adjustment, the hazard ratios (95% confidence intervals) of all-cause mortality in the highest dietary BCAA and isoleucine intake quintile (reference: lowest quintiles) were 0.68 (0.48–0.97) and 0.68 (0.48–0.97), respectively. Each one-standard-deviation increase in total dietary BCAA or isoleucine intake was associated with an 18% or 21% decrease in the risk of all-cause mortality, respectively. The serum triglyceride (TG) concentration was found to modify the association between the dietary BCAA intake and all-cause mortality (P for interaction = 0.008). Conclusions: In a nationally representative cohort, higher dietary intakes of BCAAs and isoleucine were independently associated with a lower risk of all-cause mortality, and these associations were stronger in participants with higher serum TG concentrations.

Effects of Porcine Whole-Blood Protein Hydrolysate on Exercise Function and Skeletal Muscle Differentiation

A number of studies have utilized blood waste as a bioresource by enzymatic hydrolysis to obtain amino acids, such as branched-chain amino acids, which can increase muscle mass or prevent muscle loss during weight loss. Although a significantly high content of branched-chain amino acids has been reported in porcine whole-blood protein hydrolysate (PWBPH), the effects of PWBPH on skeletal muscle differentiation and exercise function remain unclear. In this study, we investigated the effects of PWBPH on exercise endurance in ICR mice and muscle differentiation in C2C12 mouse myoblasts and gastrocnemius (Gas) muscle of mice. Supplementation with PWBPH (250 and 500 mg/kg for 5 weeks) increased the time to exhaustion on a treadmill. PWBPH also increased the Gas muscle weight to body weight ratio. In addition, PWBPH treatment increased skeletal muscle differentiation proteins and promoted the Akt/mTOR-dependent signaling pathway in vitro and in vivo. These results suggest that PWBPH can be utilized as a bioresource to enhance exercise function and skeletal muscle differentiation.