Abstract
As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, and inflammation, along with intermediate metabolites generated in their catabolism. The increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxidation, the tricarboxylic acid cycle (TCA) cycle, and oxidative phosphorylation. BCAAs can directly activate the mammalian target of rapamycin (mTOR) signaling pathway to induce insulin resistance, or function together with fatty acids. In addition, elevated levels of BCAAs and fatty acids can activate the canonical nuclear factor-κB (NF-κB) signaling pathway and inflammasome and regulate mitochondrial dysfunction and metabolic disorders through upregulated inflammatory signals. This review provides a comprehensive summary of the mechanisms through which BCAAs and fatty acids modulate energy metabolism, insulin sensitivity, and inflammation synergistically.
Highlights
Carbohydrates, lipids, and amino acids are the three major nutrients for humans
The accumulation of branched-chain amino acids (BCAAs) intermediate metabolites such as C3, C5 acylcarnitine, and acetyl-CoA inhibited the complete oxidation of fatty acids [33, 37]. These findings indicated that the coordinated roles between BCAAs and fatty acids may be critical for the pathogenesis of several metabolic diseases
In this review, we focused on the function and molecular mechanism of coordinated modulation of mitochondrial function, Insulin resistance (IR), and inflammation by BCAAs and fatty acids, in order to better understand the pathogenesis of endocrine and metabolic diseases
Summary
Carbohydrates, lipids, and amino acids are the three major nutrients for humans. They are oxidized, and they supply energy in various ways to maintain activities of the body. Elevated levels of fatty acids could interfere with the insulin signal transduction through regulating inflammation and oxidative stress, leading to the occurrence of IR [30, 31]. BCAAs and their intermediate metabolites such as C3 and C5 acylcarnitine, acetyl-CoA, succinyl-CoA, and 3hydroxyisobutyrate (3-HIB), for example, are involved in insulin signal transduction, fatty acid oxidation, tricarboxylic acid (TCA) cycle, glycolysis, mitochondrial biogenesis, inflammation, and other physiological processes [35,36,37].
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