Isoleucine
Isoleucine, one of the nine essential amino acids, is a branched-chain amino acid (BCAA) that is crucial for protein synthesis and energy production. It is not synthesized by the human body and must be obtained through diet. Sources of isoleucine include meat, fish, poultry, eggs, dairy products, nuts, seeds, and legumes.
In the human body, isoleucine is involved in muscle metabolism and is heavily concentrated in muscle tissue. It is also significant in hemoglobin synthesis and regulation of blood sugar and energy levels. Isoleucine's role as a BCAA makes it vital for repairing muscle tissue, especially after exercise, and in the maintenance of healthy muscle mass, which tends to decline with age.
Insulin resistance
Isoleucine, like other branched-chain amino acids, is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans.[1] In diet-induced obese and insulin resistant mice, a diet with decreased levels of isoleucine (with or without the other branched-chain amino acids) results in reduced adiposity and improved insulin sensitivity.[2][3] Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet.[3] In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.[4] Mice fed a low isoleucine diet are leaner, live longer, and are less frail.[5] In humans, higher dietary levels of isoleucine are associated with greater body mass index.[3]
Isoleucine and Longevity
See Also
Todo
- 2023, Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice [6]
References
- ↑ Lynch CJ & Adams SH: Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol 2014. (PMID 25287287) [PubMed] [DOI] [Full text] Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM.
- ↑ Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW; "Restoration of metabolic health by decreased consumption of branched-chain amino acids" , https://doi.org/10.1113/JP275075
- ↑ 3.0 3.1 3.2 Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, Jang C, Kasza I, Nikodemova M, Wakai MH, Tomasiewicz JL, Yang SE, Miller BR, Pak HH, Brinkman JA, Rojas JM, Quinn WJ, Cheng EP, Konon EN, Haider LR, Finke M, Sonsalla M, Alexander CM, Rabinowitz JD, Baur JA, Malecki KC, Lamming DW; "The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine" , https://doi.org/10.1016/j.cmet.2021.03.025
- ↑ Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW; "Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health" , https://doi.org/10.1016/j.celrep.2016.05.092
- ↑ Green CL, Trautman ME, Chaiyakul K, Jain R, Alam YH, Babygirija R, Pak HH, Sonsalla MM, Calubag MF, Yeh CY, Bleicher A, Novak G, Liu TT, Newman S, Ricke WA, Matkowskyj KA, Ong IM, Jang C, Simcox J, Lamming DW; "Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice" , https://doi.org/10.1016/j.cmet.2023.10.005
- ↑ Green CL et al.: Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice. Cell Metab 2023. (PMID 37939658) [PubMed] [DOI] [Full text] Low-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates many of these benefits in young C57BL/6J mice. Restriction of dietary isoleucine (IleR) is sufficient to promote metabolic health and is required for many benefits of a low-protein diet in C57BL/6J males. Here, we test the hypothesis that IleR will promote healthy aging in genetically heterogeneous adult UM-HET3 mice. We find that IleR improves metabolic health in young and old HET3 mice, promoting leanness and glycemic control in both sexes, and reprograms hepatic metabolism in a sex-specific manner. IleR reduces frailty and extends the lifespan of male and female mice, but to a greater degree in males. Our results demonstrate that IleR increases healthspan and longevity in genetically diverse mice and suggests that IleR, or pharmaceuticals that mimic this effect, may have potential as a geroprotective intervention.