Kelly, T., Yang, W., Chen, C. S., Reynolds, K. & He, J. Global burden of obesity in 2005 and projections to 2030. Int. J. Obes. 32(9), 1431–1437 (2008).
Shaw, J. E., Sicree, R. A. & Zimmet, P. Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract. 87, 4–14 (2010).
Cai, Q. et al. Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. Diabetes Care 43(7), 1392–1398 (2020).
Lynch, C. J. & Adams, S. H. Banched-chain amino acids in metabolic signalling and Insulin resistance. Nat. Rev. Endocrinol. 10(12), 723–736 (2014).
Wang, T. J. et al. Metabolite profiles and the risk of developing diabetes. Nat. Med. 17(4), 448–453 (2011).
Biswas, D. et al. Branched-chain ketoacid overload inhibits insulin action in the muscle. J. Biol. Chem. 295(46), 15597–15621. https://doi.org/10.1074/jbc.RA120.013121 (2020).
Tricò, D. et al. Elevated a-hydroxybutyrate and branched-chain amino acid levels predict deterioration of glycemic control in adolescents. J. Clin. Endocrinol. Metab. 102(7), 2473–2481 (2017).
White, P. J. et al. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export. Mol. Metab. 5(7), 538–551. https://doi.org/10.1016/j.molmet.2016.04.006 (2016).
White, P. J. et al. The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase. Cell Metab. 27(6), 1281–1293. https://doi.org/10.1016/j.cmet.2018.04.015 (2018).
Felig, P., Marliss, E. & Cahill, G. F. Plasma amino acid levels and insulin secretion in obesity. N. Engl. J. Med. 1(9), 39–42 (1969).
Newgard, C. B. et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9(4), 311–326. https://doi.org/10.1016/j.cmet.2009.02.002 (2009).
Tobias, D. K. et al. Fasting status and metabolic health in relation to plasma branched chain amino acid concentrations in women. Metabolism 117, 154391. https://doi.org/10.1016/j.metabol.2020.154391 (2021).
Newgard, C. B. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab. 15(5), 606–614. https://doi.org/10.1016/j.cmet.2012.01.024 (2012).
Kubacka, J., Cembrowska, P., Sypniewska, G. & Stefanska, A. The association between branched-chain amino acids (Bcaas) and cardiometabolic risk factors in middle-aged caucasian women stratified according to glycemic status. Nutrients 13(10), 3307 (2021).
Wilkinson, D. J. et al. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. J. Physiol. 591(11), 2911–2923 (2013).
Hernández-Alvarez, M. I. et al. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism. Sci. Rep. 7(1), 1–12 (2017).
David, J., Dardevet, D., Mosoni, L., Savary-Auzeloux, I. & Polakof, S. Impaired skeletal muscle branched-chain amino acids catabolism contributes to their increased circulating levels in a non-obese insulin-resistant fructose-fed rat model. Nutrients 11(2), 1–13 (2019).
Crossland, H. et al. Exploring mechanistic links between extracellular branched-chain amino acids and muscle insulin resistance: An in vitro approach. Am. J. Physiol. Cell Physiol. 319(6), C1151–C1157 (2020).
Lim, E. L., Lim, K., Hollingsworth, K. G. & Aribisala, B. S. Reversal of type 2 diabetes: Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54, 2506–2514 (2011).
Lean, M. E. et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): An open-label, cluster-randomised trial. Lancet 391(10120), 541–551. https://doi.org/10.1016/S0140-6736(17)33102-1 (2018).
Hong, K., Li, Z., Wang, H. J., Elashoff, R. & Heber, D. Analysis of weight loss outcomes using VLCD in black and white overweight and obese women with and without metabolic syndrome. Int. J. Obes. 29(4), 436–442 (2005).
Willi, S. M., Martin, K., Datko, F. M. & Brant, B. P. Treatment of type 2 diabetes in childhood using a very-low-calorie diet. Diabetes Care 27(2), 348–353 (2004).
Phillips, B., Williams, J. P., Greenhaff, P. L., Smith, K. & Atherton, P. J. Physiological adaptations to resistance exercise as a function of age. JCI Insight 2(17), 1–16 (2017).
Muscogiuri, G. et al. The management of very low-calorie ketogenic diet in obesity outpatient clinic: A practical guide. J. Transl. Med. 17(1), 1–9. https://doi.org/10.1186/s12967-019-2104-z (2019).
Goday, A. et al. Short-Term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr. Diabetes 6(9), e230 (2016).
Colleluori, G. et al. Aerobic plus resistance exercise in obese older adults improves muscle protein synthesis and preserves myocellular quality despite weight loss. Cell Metab. 30(2), 261-273.e6 (2019).
La Vignera, S. et al. The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: A single-arm uncontrolled study. Endocrine https://doi.org/10.1007/s12020-020-02518-8 (2020).
Siddik, M. A. B. & Shin, A. C. Recent progress on branched-chain amino acids in obesity, diabetes, and beyond. Endocrinol. Metab. 34(3), 234–246 (2019).
Le Couteur, D. G. et al. Branched chain amino acids, cardiometabolic risk factors and outcomes in older men: The concord health and ageing in men project. J. Gerontol. Ser. A 75(10), 1–6 (2019).
Pietiläinen, K. H. et al. Global transcript profiles of fat in monozygotic twins discordant for BMI: Pathways behind acquired obesity. PLoS Med. 5(3), 0472–0483 (2008).
Shah, S. H. et al. Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia 55(2), 321–330 (2012).
Tai, E. S. et al. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia 53(4), 757–767 (2010).
Mihalik, S. J. et al. Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: Evidence for enhanced mitochondrial oxidation. Diabetes Care 35(3), 605–611 (2012).
Menni, C. et al. Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach. Diabetes 62(12), 4270–4276 (2013).
Lips, M. A. et al. Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes. Diabetes Care 37(12), 3150–3156 (2014).
Laferrère, B. et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 93(7), 2479–2485 (2008).
Magkos, F. et al. Effect of roux-en-y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabolism. Diabetes 62(8), 2757–2761 (2013).
She, P., Reid, T., Huston, S., Cooney, R. & Lynch, C. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched chain amino acid (BCAA) metabolism. Am. J. Physiol. Endocrinol. Metab. 293(1), 1–7 (2007).
Steenackers, N., Gesquiere, I. & Matthys, C. The relevance of dietary protein after bariatric surgery: What do we know?. Curr. Opin. Clin. Nutr. Metab. Care 21(1), 58–63 (2018).
Ferreira Nicoletti, C. et al. Protein and amino acid status before and after bariatric surgery: A 12-month follow-up study. Surg. Obes. Relat. Dis. 9(6), 1008–1012. https://doi.org/10.1016/j.soard.2013.07.004 (2013).
Elshorbagy, A. K. et al. Food overconsumption in healthy adults triggers early and sustained increases in serum branched-chain amino acids and changes in cysteine linked to fat gain. J. Nutr. 148(7), 1073–1080 (2018).
Jang, C. et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat. Med. 22(4), 421–426 (2016).
Sayda, M. H. et al. Associations between plasma branched chain amino acids and health biomarkers in response to resistance exercise training across age. Nutrients 12(10), 3029 (2020).
She, P. et al. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 6(3), 181–194 (2007).
Wang, Q., Holmes, M. V., Smith, G. D. & Ala-Korpela, M. Genetic support for a causal role of insulin resistance on circulating branched-chain amino acids and inflammation. Diabetes Care 40(12), 1779–1786 (2017).
Hammer, S. et al. Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J. Am. Coll. Cardiol. 52(12), 1006–1012 (2008).
Heiskanen, M. A. et al. Exercise training decreases pancreatic fat content and improves beta cell function regardless of baseline glucose tolerance: A randomised controlled trial. Diabetologia 61(8), 1817–1828 (2018).
Keating, S. E., Hackett, D. A., George, J. & Johnson, N. A. Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis. J. Hepatol. 57(1), 157–166. https://doi.org/10.1016/j.jhep.2012.02.023 (2012).
link