title: Improved Insulin Sensitivity 3 Months After RYGB Surgery Is Associated With Increased Subcutaneous Adipose Tissue AMPK Activity and Decreased Oxidative Stress.
abstract: Morbidly obese individuals are predisposed to a wide range of disorders, including type 2 diabetes, atherosclerotic cardiovascular disease, fatty liver disease, and certain cancers. Remarkably, all of these disorders can be improved or prevented by Roux-en-Y gastric bypass (RYGB) surgery. We have reported that decreased AMPK activity, together with increased oxidative stress and inflammation in adipose tissue, is associated with insulin resistance in morbidly obese bariatric surgery patients. In the current study, we assessed how these parameters are affected by RYGB surgery. Eleven patients (average age of 46 ± 4 years) were studied immediately prior to surgery and 3 months postoperatively. We measured subcutaneous adipose tissue AMPK phosphorylation (threonine 172, an index of its activation), malonyl-CoA content, protein carbonylation (a marker of oxidative stress), plasma adiponectin, and mRNA expression of several inflammatory cytokines. After surgery, AMPK activity increased 3.5-fold and oxidative stress decreased by 50% in subcutaneous adipose tissue. In addition, malonyl-CoA levels were reduced by 80%. Furthermore, patients had improvements in their BMI and insulin sensitivity (HOMA) and had increased circulating high-molecular weight adiponectin and decreased fasting plasma insulin levels. In contrast, the expression of inflammatory markers in subcutaneous adipose tissue was unchanged postoperatively, although plasma CRP was diminished by 50%.
authors.affiliation: Diabetes and Metabolism Unit, Section of Endocrinology, Department of Medicine, Boston University School of Medicine, Boston, MA juliaxu@bu.edu.
authors.forename: X Julia
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Diabetes and Metabolism Unit, Section of Endocrinology, Department of Medicine, Boston University School of Medicine, Boston, MA Nutrition and Weight Management Center, Boston University School of Medicine, Boston, MA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Apovian
authors.affiliation: Deparment of Surgery, Boston University School of Medicine, Boston, MA.
authors.forename: Donald
authors.initials: D
authors.lastname: Hess
authors.affiliation: Deparment of Surgery, Boston University School of Medicine, Boston, MA.
authors.forename: Brian
authors.initials: B
authors.lastname: Carmine
authors.affiliation: Diabetes and Metabolism Unit, Section of Endocrinology, Department of Medicine, Boston University School of Medicine, Boston, MA.
authors.forename: Asish
authors.initials: A
authors.lastname: Saha
authors.affiliation: Diabetes and Metabolism Unit, Section of Endocrinology, Department of Medicine, Boston University School of Medicine, Boston, MA.
authors.forename: Neil
authors.initials: N
authors.lastname: Ruderman
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin; D000328:Adult; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000201:enzymology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D052242:Adiponectin; D016207:Cytokines; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases