title: Striatal dopamine homeostasis is altered in mice following Roux-en-Y gastric bypass surgery.
abstract: Roux-en-Y gastric bypass (RYGB) is an effective treatment for obesity. Importantly, weight loss following RYGB is thought to result in part from changes in brain-mediated regulation of appetite and food intake. Dopamine (DA) within the dorsal striatum plays an important role in feeding behavior; we therefore hypothesized that RYGB alters DA homeostasis in this subcortical region. In the current study, obese RYGB-operated mice consumed significantly less of a high-fat diet, weighed less by the end of the study, and exhibited lower adiposity than obese sham-operated mice. Interestingly, both RYGB and caloric restriction (pair feeding) resulted in elevated DA and reduced norepinephrine (NE) tissue levels compared with ad libitum fed sham animals. Consequently, the ratio of NE to DA, a measure of DA turnover, was significantly reduced in both of these groups. The RYGB mice additionally exhibited a significant increase in phosphorylation of tyrosine hydroxylase at position Ser31, a key regulatory site of DA synthesis. This increase was associated with augmented expression of extracellular-signal-regulated kinases ERK1/2, the kinase targeting Ser31. Additionally, RYGB has been shown in animal models and humans to improve insulin sensitivity and glycemic control. Curiously, we noted a significant increase in the expression of insulin receptor-β in RYGB animals in striatum (a glucosensing brain region) compared to sham ad libitum fed mice. These data demonstrate that RYGB surgery is associated with altered monoamine homeostasis at the level of the dorsal striatum, thus providing a critical foundation for future studies exploring central mechanisms of weight loss in RYGB.
authors: Vanderbilt University Department of Molecular Physiology and Biophysics, ‡Vanderbilt Brain Institute, §Vanderbilt University Department of Surgery, and ∥Vanderbilt Mouse Metabolic Phenotyping Center, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
authors: India A
authors: IA
authors: Reddy
authors: David H
authors: DH
authors: Wasserman
authors: Julio E
authors: JE
authors: Ayala
authors: Alyssa H
authors: AH
authors: Hasty
authors: Naji N
authors: NN
authors: Abumrad
authors: Aurelio
authors: A
authors: Galli
mesh_terms: D050154:Adiposity / Q000502:physiology; D000713:Anastomosis, Roux-en-Y; D000818:Animals; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction; D003342:Corpus Striatum / Q000503:physiopathology*; D059305:Diet, High-Fat; D004298:Dopamine / Q000378:metabolism*; D015390:Gastric Bypass; D006706:Homeostasis / Q000502:physiology; D015151:Immunoblotting; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy / Q000503:physiopathology* / Q000601:surgery*; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D011972:Receptor, Insulin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004298:Dopamine; D009638:Norepinephrine
keywords: RYGB; brain; bypass; dopamine; insulin; obesity; striatum