Delving into the Latest Updates on Branchamin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Branched Chain Amino Acid

Target-

Mechanism-

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 2Insulin ResistanceObesity

Inactive Indication

Abdominal PainAnorexia NervosaAnxiety Disorders+ [18]

Originator Organization

Mayo Clinic

Active Organization

University of Wisconsin

Inactive Organization

LSU Health Sciences Center

National Institute of Mental Health

Drug Highest PhaseEarly Phase 1

First Approval Date-

Regulation-

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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.

01 Nov 2024·Journal of Dairy Science

Effects of abomasal infusion of branched-chain amino acids or branched-chain keto-acids on liver function, inflammation, and oxidative stress in multiparous fresh cows

Article

Author: Ahmad, G ; Vandehaar, M ; Gallagher, K ; Bernstein, I ; Zhou, Z ; Lovotti, G ; Trevisi, E ; Mezzetti, M ; Daddam, J R ; Puda, E

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.

01 Oct 2024·Pharmacology Research & Perspectives

Nutritional strategies for improving sarcopenia outcomes in older adults: A narrative review

Review

Author: Goes‐Santos, Beatriz R. ; Carson, Brian P. ; da Fonseca, Guilherme Wesley Peixoto ; von Haehling, Stephan

AbstractSarcopenia is characterized by a decline in muscle strength, generalized loss of skeletal muscle mass, and impaired physical performance, which are common outcomes used to screen, diagnose, and determine severity of sarcopenia in older adults. These outcomes are associated with poor quality of life, increased risk of falls, hospitalization, and mortality in this population. The development of sarcopenia is underpinned by aging, but other factors can lead to sarcopenia, such as chronic diseases, physical inactivity, inadequate dietary energy intake, and reduced protein intake (nutrition‐related sarcopenia), leading to an imbalance between muscle protein synthesis and muscle protein breakdown. Protein digestion and absorption are also modified with age, as well as the reduced capacity of metabolizing protein, hindering older adults from achieving ideal protein consumption (i.e., 1–1.5 g/kg/day). Nutritional supplement strategies, like animal (i.e., whey protein) and plant‐based protein, leucine, and creatine have been shown to play a significant role in improving outcomes related to sarcopenia. However, the impact of other supplements (e.g., branched‐chain amino acids, isolated amino acids, and omega‐3) on sarcopenia and related outcomes remain unclear. This narrative review will discuss the evidence of the impact of these nutritional strategies on sarcopenia outcomes in older adults.

100 Deals associated with Branchamin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Abdominal Pain	Preclinical	US	LSU Health Sciences Center	01 Jun 2021
Diarrhea	Preclinical	US	LSU Health Sciences Center	01 Jun 2021
Hepatic Encephalopathy	Preclinical	US	LSU Health Sciences Center	01 Jun 2021
Hepatic Infarction	Preclinical	US	LSU Health Sciences Center	01 Jun 2021
Hypertension	Preclinical	US	LSU Health Sciences Center	01 Jun 2021
Nausea	Preclinical	US	LSU Health Sciences Center	01 Jun 2021
Anorexia Nervosa	Preclinical	US	National Institute of Mental Health	30 Jun 2006
Anxiety Disorders	Preclinical	US	National Institute of Mental Health	30 Jun 2006
Behavioural disorders	Preclinical	US	National Institute of Mental Health	30 Jun 2006
Feeding and Eating Disorders	Preclinical	US	National Institute of Mental Health	30 Jun 2006