Endocrinol Metab.  2019 Sep;34(3):234-246. 10.3803/EnM.2019.34.3.234.

Recent Progress on Branched-Chain Amino Acids in Obesity, Diabetes, and Beyond

• Siddik MA
• Shin AC

• KMID: 2458625
• DOI: http://doi.org/10.3803/EnM.2019.34.3.234

Abstract

Branched-chain amino acids (BCAAs) are essential amino acids that are not synthesized in our body; thus, they need to be obtained from food. They have shown to provide many physiological and metabolic benefits such as stimulation of pancreatic insulin secretion, milk production, adipogenesis, and enhanced immune function, among others, mainly mediated by mammalian target of rapamycin (mTOR) signaling pathway. After identified as a reliable marker of obesity and type 2 diabetes in recent years, an increasing number of studies have surfaced implicating BCAAs in the pathophysiology of other diseases such as cancers, cardiovascular diseases, and even neurodegenerative disorders like Alzheimer's disease. Here we discuss the most recent progress and review studies highlighting both correlational and potentially causative role of BCAAs in the development of these disorders. Although we are just beginning to understand the intricate relationships between BCAAs and some of the most prevalent chronic diseases, current findings raise a possibility that they are linked by a similar putative mechanism.

Keyword

Branched-chain amino acids; Metabolism; Cancers; Alzheimer disease; Heart failure

MeSH Terms

Adipogenesis
Alzheimer Disease
Amino Acids, Branched-Chain*
Amino Acids, Essential
Cardiovascular Diseases
Chronic Disease
Heart Failure
Insulin
Metabolism
Milk
Neurodegenerative Diseases
Obesity*
Sirolimus
Amino Acids, Branched-Chain
Amino Acids, Essential
Insulin
Sirolimus

Figure

• 

  Fig. 1 An overview of what is currently known about the role of branched-chain amino acids (BCAAs) or their derived keto-acids (i.e., branched-chain keto acids [BCKAs]) in different disease states and their potential molecular mechanisms. It is interesting to note that most studies reveal higher circulating levels of BCAAs in each disease. Items in dark blue shapes indicate mechanistic interventions based on recent studies. CNS, central nervous system; pmTOR, phosphorylated mammalian target of rapamycin; pAKT, phosphorylated protein kinase B; BCAT1, cytoplasmic branched-chain amino acid transaminase; KO, knockout; BT2, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid; BCKDH, branched-chain α-keto acid dehydrogenase.

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