The rate of obesity increased dramatically over the course of the last half century. In the United States, non-Hispanic black women have experienced a particularly high risk to develop obesity. The consequences of the epidemic for public health are both direct, like the increased prevalence of obstructive sleep apnea, and indirect, like the increased prevalence of diabetes and cancer. Combined, obesity significantly elevates mortality risk. To reverse these risks, bariatric surgeries like sleeve gastrectomy, have been effective in yielding long-term weight loss alongside substantially improved metabolic health. Yet, the specific mechanisms and specific organs that contribute to improvements in metabolic health after post-surgery are not yet clear. Nor are the changes that stall or eventually reverse the weight loss and metabolic improvements. We have evidence that there are alterations in insulin responsiveness in subcutaneous adipose tissue at two weeks post-surgery. Therefore, we became interested in creating a more detailed picture of subcutaneous adipose tissue metabolic alterations shortly after sleeve gastrectomy. We enrolled ten women who were scheduled for sleeve gastrectomy surgery following informed written consent. Despite not having diabetes, subjects did have substantial reductions in fasting serum glucose, fasting insulin, and systemic insulin sensitivity at twelve weeks following surgery. Subjects consumed roughly one-fourth of the baseline calories per day. We show upregulation of hDBP expression in parallel with several other elements of adipose tissue circadian clock in association with caloric restriction. Upregulation of hNPAS2, appeared to be associated additionally with changes to systemic insulin sensitivity. We showed phase delay of insulin signaling genes (INSR, IRS1, PIK3.CA) and lipid regulatory gene INSIG2. Further, we showed down regulation in adipokine genes (LEPTIN, ADIPOQ) and lipolysis gene (ATGL), and upregulation of master transcription factor genes (SREBP1 and PGC1α) and insulin pathway genes (INSR, IRS1, GLUT4, SOCS3). A majority of the changes could be explained by caloric restriction with expected declines in fasting insulin and systemic insulin sensitivity. Surgery did not associate with change to INSIG2, but caloric restriction and associated upregulated lipolysis were associated.
|Advisor:||Brady, Matthew J.|
|Commitee:||Fang, Yun, Cohen, Ronald, Knutson, Kristen|
|School:||The University of Chicago|
|Department:||Molecular Metabolism and Nutrition|
|School Location:||United States -- Illinois|
|Source:||DAI-A 82/6(E), Dissertation Abstracts International|
|Subjects:||Surgery, Nutrition, Medicine, Public health, Health sciences, Womens studies, Genetics, Black studies, Histology|
|Keywords:||Adipose tissue, Circadian clock, Glucose regulation, Obesity rate, Sleep cycle, Sleeve gastrectomy, United States, Non-Hispanic Black women, High-risk populations, Epidemic, Lipid regulatory gene, Systemic insulin sensitivity|
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