title: Branched-chain amino acids alter neurobehavioral function in rats.
abstract: Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders.
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27704, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Coppola
authors.forename: Brett R
authors.initials: BR
authors.lastname: Wenner
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Mauro
authors.initials: M
authors.lastname: Maggioni
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000009:adverse effects* / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D005106:Exploratory Behavior; D007736:Kynurenic Acid / Q000378:metabolism; D008297:Male; D019964:Mood Disorders / Q000209:etiology; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism / Q000627:therapeutic use; D015430:Weight Gain
chemical_list: D000597:Amino Acids, Branched-Chain; D019422:Dietary Sucrose; D012701:Serotonin; D014364:Tryptophan; D007736:Kynurenic Acid