Branchamin

The adverse metabolic impacts of branched-chain amino acids (BCAA) have been elucidated are mediated by isoleucine and valine. Dietary restriction of isoleucine promotes metabolic health and increases lifespan. However, a high protein diet enriched in BCAA is presently the most useful therapeutic strategy for nonalcoholic fatty liver disease (NAFLD), yet, its underlying mechanism remains largely unknown. Fatty liver hemorrhagic syndrome (FLHS), a specialized laying hen NAFLD model, can spontaneously develop fatty liver and hepatic steatosis under a high-energy and high-protein dietary background that the pathogenesis of FLHS is similar to human NAFLD. The mechanism underlying dietary BCAA control of NAFLD development in laying hens remains unclear. Herein, we demonstrate that dietary supplementation with 67 % High BCAA has unique mitigative impacts on NAFLD in laying hens. A High BCAA diet alleviates NAFLD, by inhibiting the tryptophan-ILA-AHR axis and MAPK9-mediated de novo lipogenesis (DNL), promoting ketogenesis and energy metabolism, and activating PPAR-RXR and pexophagy to promote fatty acid β-oxidation. Furthermore, we uncover that High BCAA strongly activates ubiquitin-proteasome autophagy via downregulating UFMylation to trigger MAPK9-mediated DNL, fatty acid elongation and lipid droplet formation-related proteins ubiquitination degradation, activating PPAR-RXR and pexophagy mediated fatty acid β-oxidation and lipolysis. Together, our data highlight moderating intake of high BCAA by inhibiting the AHR/MAPK9 are promising new strategies in NAFLD and FLHS treatment.

Reduced liver function, increased oxidative stress, and inflammation in early lactation negatively affect lactation performance and health of fresh cows. Previous findings from our group demonstrated that branched-chain AA (BCAA) infusion improved lactation performance and branched-chain keto-acids (BCKA) infusion decreased liver triglyceride (TG) in fresh cows. The objectives of this study were to determine the effect of BCAA and BCKA on blood and liver biomarkers of liver function, oxidative stress, and inflammation as well as expression of genes regulating inflammation and antioxidant metabolism in the liver. Thirty multiparous Holstein cows were used in a randomized block design receiving continuous abomasal infusion for 21 d after parturition. Treatments (10 cows each) were control (CON), cows abomasally infused with 0.9% saline; cows abomasally infused with BCAA (67 g valine, 50 g leucine, and 34 g isoleucine; BCA); and cows abomasally infused with BCKA (77 g keto-valine, 57 g keto-leucine, and 39 g keto-isoleucine; BCK). All cows were randomly assigned to treatments after parturition and received the same diet throughout the experimental period. Blood was collected at 3, 7, 14, and 21 d postpartum for liver function, oxidative stress, and inflammation biomarker profiling. Liver was also harvested on 7, 14, and 21 d postpartum for quantification of glutathione, protein carbonylation, and expression of genes. ANOVA was conducted for all data using PROC GLIMMIX in SAS. No treatment differences were observed for liver function biomarkers (bilirubin, gamma-glutamyl transferase, and aspartate aminotransferase). Cows receiving BCAA had lower blood NO₂^- and NO₃^- concentrations compared with CON. A tendency for lower advanced oxidized protein products was also observed in BCA cows compared with CON. Additionally, on d 7, BCA cows had lower protein carbonylation in the liver compared with CON. In contrast, BCK cows had higher plasma thiol and albumin, as well as liver reduced and total glutathione compared with CON cows. Compared with CON, BCK cows had higher expression glutathione reductase in the liver. Overall, these results suggest favorable alterations in oxidative stress and inflammation status in fresh cows receiving BCAA or BCKA infusion during the first 3 wk of lactation, which likely contributed to previously-observed changes in lactation performance and liver TG concentrations. Future work is required to evaluate the interrelated metabolism of BCAA and BCKA to better understand their effects on oxidative and immune metabolism.