Fat Mass Regain in Middle-Aged Mice after Sleeve Gastrectomy is divergent from plasma leptin levels

Abstract

BackgroundSome degree of weight regain is typically observed in human patients who undergo Sleeve Gastrectomy (SG), even if the majority of them do not return to their presurgical body weight. Although the majority of bariatric surgery patients are middle aged, most preclinical models of bariatric surgery utilize juvenile male mice. A long-term characterization of the response of mature, wild type, obese male mice to SG has not been performed. MethodsEight-month old C57bl/6J obese male mice were randomized to undergo SG, sham surgery without caloric restriction (SH) or sham surgery with caloric restriction to match body weight to the SG group (SWM). Body weight, body composition and glucose tolerance were matched at baseline. Mice were followed for 60 days following their respective surgeries. ResultsSG mice had a more pronounced percent weight loss than the SH group in the first post-operative month (p<0.05), along with fat mass loss (p<0.01). By the second post-operative month, the SG group started to regain fat mass, although it continued to be statistically lower than the SH group (p<0.05). Cumulative food intake was significantly lower in the SG group compared to SH group only in the first post-operative week (p<0.05), with both groups having similar cumulative food intake thereafter (p>0.05). SWM group had a significantly lower cumulative food intake throughout the study, except for week 1 (p<0.01). Glucose tolerance was only demonstrably better in the SG group compared to SH group at 8 weeks post-operatively (p<0.01). Plasma leptin was significantly lower in the SG group compared to both SWM and SH groups group by the second post-operative month (p<0.01), in spite of SGs increasing fat mass accumulation. In the second post-operative month, both FGF-21 and GDF-15 were increased in the SH group compared to the SG and SWM groups (p<0.05), while there was no difference in plasma insulin among the three groups. Heat production was surprisingly higher in the SH group compared to the other two groups (p<0.05), even though brown adipose tissue Peroxisome Proliferator-Activated Receptor Gamma (PPARg) and Cidea mRNA expression were significantly higher in SG and SWM compared to SH (p<0.01). There was no change in BAT UCP-1 mRNA expression among the groups (p>0.05). There was also no change in fecal lipid content among the groups (p>0.05). ConclusionsSG in obese, middle aged male mice leads is accompanied by fat mass regain in the second post-operative month, while plasma leptin levels continue to be significantly lower. This raises the question of whether the observed fat mass regain consists mostly of visceral adipose tissue.