Henchion M, Hayes M, Mullen AM, Fenelon M, Tiwari B. Future protein supply and demand: strategies and factors influencing a sustainable equilibrium. Foods. 2017;6:53.

Article  PubMed  PubMed Central  Google Scholar 

Lynch CJ, Gern B, Lloyd C, Hutson SM, Eicher R, Vary TC. Leucine in food mediates some of the postprandial rise in plasma leptin concentrations. Am J Physiol Endocrinol Metab. 2006;291:E621–30.

Article  CAS  PubMed  Google Scholar 

Chen Q, Reimer RA. Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro. Nutrition. 2009;25:340–9.

Article  PubMed  Google Scholar 

Torres-Leal FL, Fonseca-Alaniz MH, Teodoro GF, de Capitani MD, Vianna D, Pantaleao LC, et al. Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet. Nutr Metab. 2011;8:62.

Article  CAS  Google Scholar 

Estrada-Alcalde I, Tenorio-Guzman MR, Tovar AR, Salinas-Rubio D, Torre-Villalvazo I, Torres N, et al. Metabolic fate of branched-chain amino acids during adipogenesis, in adipocytes from obese mice and C2C12 myotubes. J Cell Biochem. 2017;118:808–18.

Article  CAS  PubMed  Google Scholar 

Wallace M, Green CR, Roberts LS, Lee YM, McCarville JL, Sanchez-Gurmaches J, et al. Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues. Nat Chem Biol. 2018;14:1021–31.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mao X, Qi S, Yu B, He J, Yu J, Chen D. Zn(2+) and L-isoleucine induce the expressions of porcine beta-defensins in IPEC-J2 cells. Mol Biol Rep. 2013;40:1547–52.

Article  CAS  PubMed  Google Scholar 

Rivas-Santiago CE, Rivas-Santiago B, Leon DA, Castaneda-Delgado J, Hernandez Pando R. Induction of beta-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis. Clin Exp Immunol. 2011;164:80–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Drummond MJ, Rasmussen BB. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care. 2008;11:222–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kreider RB. Dietary supplements and the promotion of muscle growth with resistance exercise. Sports Med. 1999;27:97–110.

Article  CAS  PubMed  Google Scholar 

Layman DK. Role of leucine in protein metabolism during exercise and recovery. Can J Appl Physiol. 2002;27:646–63.

Article  CAS  PubMed  Google Scholar 

Bower RH, Muggia-Sullam M, Vallgren S, Hurst JM, Kern KA, LaFrance R, et al. Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial. Ann Surg. 1986;203:13–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chin SE, Shepherd RW, Thomas BJ, Cleghorn GJ, Patrick MK, Wilcox JA, et al. Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement. Am J Clin Nutr. 1992;56:158–63.

Article  CAS  PubMed  Google Scholar 

Choudry HA, Pan M, Karinch AM, Souba WW. Branched-chain amino acid-enriched nutritional support in surgical and cancer patients. J Nutr. 2006;136:314S–8S.

Article  CAS  PubMed  Google Scholar 

Matsuoka S, Tamura A, Nakagawara H, Moriyama M. Improvement in the nutritional status and clinical conditions of patients with liver failure using a liver diet combined with a branched chain amino acids-enriched elemental diet. Hepatogastroenterology. 2014;61:1308–12.

CAS  PubMed  Google Scholar 

Tietze IN, Pedersen EB. Effect of fish protein supplementation on aminoacid profile and nutritional status in haemodialysis patients. Nephrol Dial Transpl. 1991;6:948–54.

Article  CAS  Google Scholar 

Tsien C, Davuluri G, Singh D, Allawy A, Ten Have GA, Thapaliya S, et al. Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology. 2015;61:2018–29.

Article  CAS  PubMed  Google Scholar 

Jang C, Oh SF, Wada S, Rowe GC, Liu L, Chan MC, et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med. 2016;22:421–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lerin C, Goldfine AB, Boes T, Liu M, Kasif S, Dreyfuss JM, et al. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism. Mol Metab. 2016;5:926–36.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moghei M, Tavajohi-Fini P, Beatty B, Adegoke OA. Ketoisocaproic acid, a metabolite of leucine, suppresses insulin-stimulated glucose transport in skeletal muscle cells in a BCAT2-dependent manner. Am J Physiol Cell Physiol. 2016;311:C518–27.

Article  PubMed  PubMed Central  Google Scholar 

Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9:311–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab. 2007;293:E1552–63.

Article  CAS  PubMed  Google Scholar 

Zhang F, Zhao S, Yan W, Xia Y, Chen X, Wang W, et al. Branched chain amino acids cause liver injury in obese/diabetic mice by promoting adipocyte lipolysis and inhibiting hepatic autophagy. EBioMedicine. 2016;13:157–67.

Article  PubMed  PubMed Central  Google Scholar 

Adams SH, Hoppel CL, Lok KH, Zhao L, Wong SW, Minkler PE, et al. Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J Nutr. 2009;139:1073–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim JY, Park JY, Kim OY, Ham BM, Kim HJ, Kwon DY, et al. Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). J Proteome Res. 2010;9:4368–75.

Article  CAS  PubMed  Google Scholar 

Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG, et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity. 2010;18:1695–700.

Article  CAS  PubMed  Google Scholar 

Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17:448–53.

Article  PubMed  PubMed Central  Google Scholar 

Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, et al. Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol. 2018;596:623–45.

Article  CAS  PubMed  Google Scholar 

Costa Junior JM, Rosa MR, Protzek AO, de Paula FM, Ferreira SM, Rezende LF, et al. Leucine supplementation does not affect protein turnover and impairs the beneficial effects of endurance training on glucose homeostasis in healthy mice. Amino Acids. 2015;47:745–55.

Article  PubMed  Google Scholar