Downregulation of Leptin and Resistin Expression in Blood Following Bariatric Surgery

Introduction: Morbidly obese patients are at increased risk for developing type 2 diabetes (T2D). Interestingly, T2D resolves rapidly after bariatric surgery, even before substantial weight is lost. However, the underlying molecular pathways by which T2D resolves after bariatric surgery remain unclear. Previous microarray data has shown the genes for leptin and resistin are differentially expressed in diabetic vs. nondiabetic and pre vs. post op groups of patients undergoing bariatric surgery. Both leptin and resistin are derived from adipose tissue, circulate in the blood, and are associated with obesity and insulin resistance. This study examines expression of these genes pre- and post-operatively in diabetic and non-diabetic morbidly obese patients undergoing bariatric surgery.

Methods: The study included eight morbidly obese patients undergoing bariatric surgery including laparoscopic gastric bypass or an adjustable band. Four patients were diabetic, requiring oral medication for glucose control. Pre- and post-operative blood samples were collected and incubated in PAXgene tubes (PreAnalytix) in order to stabilize the mRNA expression. Post-operative samples were collected approximately three months after surgery. Blood samples were also collected from four non-obese, non-diabetic volunteers. Total RNA was extracted and purified (PreAnalytix, Qiagen) according to the manufacturer’s protocol, then cDNA was synthesized using the iScript cDNA Synthesis Kit (Bio-Rad Laboratories). Finally, real time quantitative PCR (ABI 7300 System) was used to quantify gene expression. Results were analyzed using Student’s t-test with a p<0.05 significant.

Results: At three months post-operatively, three of the morbidly obese diabetic patients had discontinued hypoglycemic medications while the fourth patient showed improved glycemic control with fewer medications. Post-operatively, mean leptin expression was decreased for all morbidly obese patients. However, this value was not significantly decreased (p=0.16). Post-operatively, mean resistin expression was unchanged for the entire cohort (p=0.36). However, resistin expression was significantly lower (p=0.05) after surgery in diabetic morbidly obese patients. Post-operative resistin expression in non-diabetic morbidly obese patients was not significantly different from pre-op values (p=0.32).

Conclusions: This unique data shows that decreased gene expression of resistin and leptin may play a significant role in normalizing insulin resistance in morbidly obese patients following bariatric surgery. Also, this preliminary data suggests that modulation of resistin expression plays a role in diabetic obese patients and not necessarily in morbidly obese patients without T2D. Patient recruitment is ongoing to further elucidate these trends. Specific understanding of the pathways by which these adipocytokines contribute to both obesity and T2D could potentially lead to novel therapies for these conditions.

Session: Podium Presentation

Program Number: S013

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