Diet-dependent sex differences in the response to vertical sleeve gastrectomy

Abstract

Nearly 80% of patients that receive bariatric surgery are women, yet mechanistic pre-clinical studies have focused on males. The goal of this study was to determine the metabolic impact of diet- and surgery-induced weight loss in males, females, and ovariectomized females. Male and female mice were fed a 60% high-fat (HFD) diet before undergoing either vertical sleeve gastrectomy (VSG) or sham surgery. Mice either remained on HFD or were switched to a standard chow diet post-surgically. When maintained on HFD, both males and females decreased fat mass and improved oral glucose tolerance after VSG. After dietary intervention, additional adiposity was lost in both surgical groups. Ovariectomized females had a blunted decrease in fat mass on a HFD, but lost significant adiposity after dietary intervention. Energy expenditure was only impacted by dietary but not surgical intervention across all groups. Males decreased hepatic triglyceride levels after VSG, which was further decreased after dietary intervention. Intact and ovariectomized females had a blunted decrease in hepatic triglycerides after surgical intervention but a significant decrease after dietary intervention. The more pronounced effect of surgery on hepatic lipids in males was strongly associated with changes in expression of hepatic microRNAs and genes that have previously been linked to hepatic lipid regulation and systemic energy homeostasis. These data highlight the importance of post-surgical diet on metabolic outcomes across sexes and hormone levels. Furthermore, these data suggest the impact of VSG on hepatic triglycerides is diet-dependent in females and support that hypothesis that males and females achieve a similar metabolic outcome, at least within the liver, via distinct mechanisms.

Changes in gut microbiota, metabolite SCFAs, and GPR43 expression in obese diabetic mice after sleeve gastrectomy

“…Among the various surgeries available, SG has become increasingly popular owing to its positive effects and relatively simple and safe surgical method (Peterli et al, 2018). Currently, many mouse models are available to study the mechanisms by which metabolic surgery treats obesity and diabetes (Ding et al, 2021; Hutch et al, 2021). DIO and ob mice represented two types of obesity and responded differently to RYGB surgery (Hao et al, 2015; Mokadem et al, 2015).…”

Intestinal epithelial adaptations to vertical sleeve gastrectomy defined at single-cell resolution

“…To better understand how diet and bariatric surgery impact the small intestinal epithelium, we first initiated male C57BL/6J mice on a 16-week high-fat diet (HFD) regimen followed by surgical intervention (Figure 1A). Upon induction of diet-induced obesity, HFD fed mice underwent vertical sleeve gastrectomy (VSG), resulting in improved metabolic outcomes compared to their sham-operated counterparts as expected from previous studies in both murine models 15,16 and human patients 10,17 . Within one-week post-surgery, HFD VSG animals lost significantly more body weight than HFD sham mice, reaching weights comparable to that approached those of a parallel group of sham mice fed a low-fat diet (LFD) (Figure 1B).…”

Lactation from the inside out: Maternal homeorhetic gastrointestinal adaptations regulating energy and nutrient flow into milk production

“…As being able to study maternal gut architecture and functioning during reproductive events is limited, other research areas have to be mined for relevant findings. Studies of metabolic diseases and medical interventions have revealed sex differences in both responses and recovery as the development and pathogenesis of metabolic disorders are notably influenced by gonadal/reproductive hormones (Hutch et al, 2021). Females with early ovarian insufficiency or after they have reached menopause (hormonally similar in lacking oestradiol), have greater risk factors for developing metabolic dysfunction, in particular type 2 diabetes, with larger adipose depots, hyperglycaemia, increased liver triglycerides; all greater than in premenopausal women.…”

“…Male and female animals both see expected metabolic and body mass (loss) improvements although ovarian hormones seem necessary for the full impact as menstruating/cycling women lose more body mass in the two years following surgery than those that are post menopausal. However, in pre-clinical animal models fed high fat diets post-surgery, females were more resistant to liver lipid decreases and corresponding differences are found in human hepatic gene expression key regulators of lipid metabolism and inflammation (reviewed by Hutch et al, 2021). These observations emphasise the importance of appropriate post-surgical diets to achieve maximum benefits in the same way that there needs to be improved post lactation nutritional guidance for females.…”

“…Pregnancy and lactation outcomes following bariatric surgery in pre-clinical animal studies have been reported (reviewed by Spann and Grayson, 2020) including offspring with intrauterine growth restriction, born smaller and shorter. Lactation following vertical sleeve gastrectomy had a milk caloric content shift, with total calories from fat reduced and total calories increased from glucose, changes with unwanted negative metabolic consequences for reliant offspring, especially if they needed compensatory catch-up growth (Hutch et al, 2021). Robust physiological sex differences in metabolic responses to bariatric surgeries and interactions with diet suggest the mechanistic pathways are dependent on different hormone profiles and warrant urgent further exploration.…”