@article{PAR00017885,
  title = {{B}ranched chain amino acids at the edge between {M}endelian and complex disorders},
  author = {{H}aydar, {S}. and {L}autier, {C}. and {G}rigorescu, {F}lorin},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ranched chained amino acids ({BCAA}) are essential components of the human diet and important nutrient signals, which regain particular interest in recent years with the avenue of metabolomics studies suggesting their potential role as biomarkers. {T}here is now compelling evidence for predictive role of {BCAA} in progression of diabetes, but causality relationship is still debated concerning insulin resistance and genetic versus non genetic pathogenesis. {M}endelian randomization studies in large cohorts of diabetes indicated pathogenic role of {PPM}1{K} (protein phosphatase {M}g2+/{M}n2+ dependent 1{K}) on {C}hr 4q22.1 gene, encoding for a phosphatase that activate {BCKDH} (branched chain keto acid dehydrogenase) complex. {R}ecent studies indicated that insulin rapidly and dose-dependently regulates gene expression of the same complex, but the relationship with systemic insulin resistance and glucose levels is complex. {R}are genetic syndromes due to {M}endelian mutations in key genes in {BCAA} catabolism may be good models to understand potential role of gene of {BCAA} catabolism. {H}owever, in studying complex disorders geneticists are faced to complete new aspects of metabolic regulation complicating understanding genetics of obesity, diabetes or metabolic syndrome. {A} review of genetic syndromes of {BCAA} metabolism suggests that insulin resistance is not present, except rare cases of methylmalonic aciduria due to {MUT} (methylmalonyl-co{A} mutase) gene on {C}hr 6p12.3. {A}nother aspect that complicates understanding is the new role of central nervous system ({CNS}) in insulin resistance. {F}or long time the hypothalamic hunger/satiety neuronal system was considered a key site of nutrient regulation. {G}enes may also affect the brain rewarding system ({BRS}) that would regulate food intake by modulating the motivation to obtain food and considering hedonic properties. {N}utrigenomic and nutrigenetic investigations taking into account concurrently {BCAA} intake, metabolic regulation and gene variation have large perspectives to merge genetic and nutritional understanding in complex disorders.},
  keywords = {branched chain amino acids ; {BCAA} ; insulin resistance gene ; {M}endelian syndromes ; brain rewarding ; nutrigenomics},
  booktitle = {},
  journal = {{A}cta {E}ndocrinologica-{B}ucharest},
  volume = {14},
  numero = {2},
  pages = {238--247},
  ISSN = {1841-0987},
  year = {2018},
  DOI = {10.4183/aeb.2018.238},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00017885},
}