Objective Microarray studies identified Ch12:orf39 (Spexin) as the most dysregulated gene in obese human fat. Therefore we examined its role in obesity pathogenesis. Design and Methods Spexin effects on food intake, meal patterns, body weight, Respiratory Exchange Ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with dietary-induced obesity (DIO). Its effects on adipocyte [3H]-oleate uptake were determined. Results In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 μg/kg/day s.c) reduced caloric intake ~32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 μg/kg/day i.p.) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70μg/kg/day i.p.) demonstrated no aversive Spexin effects. Conclusions Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.

The rising prevalence of morbid obesity and the increased incidence of super-obese patients (BMI >50 kg/m2) seeking surgical treatments has led to the search for surgical techniques that provide adequate EWL with the least possible morbidity. Sleeve gastrectomy (SG) was initially added as a modification to the biliopancreatic diversion (BPD) and then combined with a duodenal switch (DS) in 1988. It was first performed laparoscopically in 1999 as part of a DS and subsequently done alone as a staged procedure in 2000. With the revelation that patients experienced weight loss after SG, interest in using this procedure as a bridge to more definitive surgical treatment has risen. Benefits of SG include the low rate of complications, the avoidance of foreign material, the maintenance of normal gastro-intestinal continuity, the absence of malabsorption and the ability to convert to multiple other operations. Reduction of the ghrelin-producing stomach mass may account for its superiority to other gastric restrictive procedures. SG should be in the armamentarium of all bariatric surgeons. Nonetheless, long-term studies are necessary to see if it is a durable procedure in the treatment of morbid obesity.