scholarly journals Vertical sleeve gastrectomy lowers kidney SGLT2 expression in the mouse

2019 ◽  
Author(s):  
Elina Akalestou ◽  
Livia Lopez-Noriega ◽  
Isabelle Leclerc ◽  
Guy A. Rutter

AbstractBackgroundBariatric surgery has been established to improve insulin sensitivity and glucose clearance, but also increases insulin and glucagon secretion. Each of the above effects have also been observed following treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors.AimTo determine whether there is an effect of bariatric surgery (Vertical Sleeve Gastrectomy; VSG) on renal SGLT2 expression in mice.MethodsEighteen lean mice underwent VSG (n=8) or sham (n=9) surgery. Glucose tolerance tests with or without treatment with the SGLT2 inhibitor dapagliflozin were performed four weeks post operatively, in order to assess if pharmacological SGLT2 inhibition has the same euglycemic effects after bariatric surgery. Kidneys were harvested from fed mice and SGLT2 expression was analysed using Quantitative reverse-transcription PCR and immunofluorescence.ResultsVSG mice displayed significantly improved glucose tolerance (AUC=103±6.8; AUC=66.6±2.9 in control and VSG mice, respectively; p<0.001), despite an absence of significant weight loss when compared to sham operated mice (p=0.37, Mann-Whitney test). Treatment of sham-operated mice with dapagliflozin (10 mg/kg) improved glucose tolerance. In contrast, dapagliflozin did not further improve glucose tolerance in VSG-operated mice. Moreover, qRT-PCR and immunofluorescence analysis on mouse kidneys demonstrated a significant lowering of SGLT2 expression at both the mRNA (n=7, p<0.0001) and protein (n=5, p=0.0007) levels four weeks after VSG.ConclusionsVertical sleeve gastrectomy in lean animals causes a significant inhibition of SGLT2 expression in the kidney cortex. These findings are in line with our previous results on the effects of Duodenal Jejunal Bypass in lean rats, and point towards a physiologically-relevant gut-kidney axis. SGLT2 inhibition may thus be an important mechanism through which bariatric surgery improves glucose tolerance in man.

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3192
Author(s):  
Chiu-Li Yeh ◽  
Po-Jen Yang ◽  
Po-Chu Lee ◽  
Jin-Ming Wu ◽  
Po-Da Chen ◽  
...  

Obesity is a health problem associated with many metabolic disorders. Weight reduction can effectively alleviate obesity-associated complications. Sleeve gastrectomy is a commonly used bariatric surgery and is considered safe and effective for improving outcomes. Glutamine (GLN) is an amino acid with anti-oxidative and anti-inflammatory properties. This study used a mouse model of sleeve gastrectomy to investigate the impacts of intravenous GLN administration on glucose tolerance and adipocyte inflammation short-term after surgery. C57BL6 male mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat for 10 weeks to induce obesity. Mice fed the high-fat diet were then assigned to a sham (SH) or sleeve gastrectomy with saline (S) or GLN (G) groups. The S group was intravenously injected with saline, while the G group was administered GLN (0.75 g/kg body weight) via a tail vein postoperatively. Mice in the experimental groups were sacrificed on day 1 or 3 after the surgery. Results showed that obesity resulted in fat accumulation, elevated glucose levels, and adipokines production. Sleeve gastrectomy aggravated expressions of inflammatory cytokine and macrophage infiltration markers, cluster of differentiation 68 (CD68), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR-1), and macrophage chemoattractant protein-1, in adipose tissues. Treatment of obese mice with GLN downregulated hepatic proteomic profiles associated with the gluconeogenesis pathway and improved glucose tolerance. Moreover, macrophage infiltration and adipose tissue inflammation were attenuated after the sleeve gastrectomy. These findings imply that postoperative intravenous GLN administration may improve glucose tolerance and attenuate inflammation shortly after the bariatric surgery in subjects with obesity.


Author(s):  
Kristi Reynolds ◽  
Lee J. Barton ◽  
Anirban Basu ◽  
Heidi Fischer ◽  
David E. Arterburn ◽  
...  

Weight loss is an effective strategy for the management of hypertension, and bariatric surgery is the most effective weight loss and maintenance strategy for obesity. The importance of bariatric surgery in the long-term management of hypertension and which operation is most effective is less clear. We compared the effectiveness of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) for remission and relapse of hypertension after surgery in the ENGAGE CVD cohort study (Effectiveness of Gastric Bypass Versus Gastric Sleeve for Cardiovascular Disease). Operations were done by 23 surgeons across 9 surgical practices. Hypertension remission and relapse were assessed in each year of follow-up beginning 30 days and up to 5 years postsurgery. We used a local instrumental variable approach to account for selection bias in the choice of VSG or RYGB. The study population included 4964 patients with hypertension at the time of surgery (n=3186 VSG and n=1778 RYGB). At 1 year, 27% of patients with RYGB and 28% of patients with VSG achieved remission. After 5 years, without accounting for relapse, 42% of RYGB and 43% of VSG patients had experienced hypertension remission. After accounting for relapse, only 17% of RYGB and 18% of VSG patients remained in remission 5 years after surgery. There were no statistically significant differences between VSG and RYGB for hypertension remission, relapse, or mean systolic and diastolic blood pressure at any time during follow-up.


Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3700-3705 ◽  
Author(s):  
Hilary E. Wilson-Pérez ◽  
Randy J. Seeley

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age. Although some of the primary symptoms of PCOS are reproductive abnormalities, including hyperandrogenism, menstrual dysfunction, and hirsutism, other metabolic disturbances are also common, including obesity and insulin resistance. Women with PCOS who have undergone weight-loss bariatric surgery have reported surprising postoperative benefits beyond weight loss, including resolution of menstrual dysfunction and improvement of hirsutism. Here, we use a chronic dihydrotestosterone (DHT) exposure model of PCOS in female rats and investigate the efficacy of a specific type of bariatric surgery, namely vertical sleeve gastrectomy (VSG), to resolve the reproductive and metabolic disturbances induced by DHT treatment. We find that VSG causes loss of body weight and body fat in DHT-treated rats but does not improve glucose tolerance or restore estrous cyclicity. Although human PCOS patients have shown decreased androgen levels after bariatric surgery, the chronic nature of DHT administration in this rat model both before and after VSG renders this effect impossible in this case. Therefore, the lack of improvement in glucose tolerance and estrous cyclicity may implicate a direct effect of androgen knockdown as a mechanism for the improvements seen in human PCOS patients after bariatric surgery. In addition, the dissociation of body weight loss without improved glucose tolerance suggests that glucose intolerance may be a body weight-independent phenomenon in women with PCOS.


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