Endocrine Abstracts

Bariatric surgery is known to improve obesity-induced systemic inflammation and glucose homeostasis, however, the exact mechanisms behind this effect are not fully understood. We have previously shown that Sodium Glucose Transporter 2 (SGLT2) is significantly inhibited in the kidney cortex following Vertical Sleeve Gastrectomy (VSG), causing a reduction in renal glucose reabsorption. In this study, we hypothesize that the observed post-operative reduction of SGLT2 is controlled by adipokines, as part of a direct kidney-adipose tissue axis. To do so, we utilised human kidney cells (HK-2) to reveal the effects of glucose, sodium, leptin, interleukin-6 (IL-6), and tumour-necrosis factor alpha (TNF-α) treatments on the expression of SGLT2, via RT-qPCR and Western Blot. Additionally, we performed VSG on high-fat diet (HFD) fed C57BL/6J mice in order to investigate changes in leptin, IL-6 and SGLT2 expression levels in kidney, liver and adipose biopsies post-operatively. Treatments of leptin (5nM) and sodium buffer, HEPES (N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid) were shown to directly upregulate the expression of SGLT2 in HK-2 cells. Leptin and IL-6 expression was significantly reduced in the adipose tissue and liver respectively, following VSG. This indicates that the observed renal SGLT2 inhibition is due to the reduction of post-operative leptin secretion, a result of either weight loss or regained leptin sensitivity. Decoding this novel axis can provide us with a new angle on post-bariatric surgery euglycemic effects, as well as a novel insight into inter-organ communication.