Weight loss by calorie restriction versus bariatric surgery differentially regulates the hypothalamo-pituitary-adrenocortical axis in male rats

Abstract

Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in 5 groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n=7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n=11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n=11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n=11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n=12). Compared to Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentrations and increased hypothalamic corticotropin releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results suggest that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches.

Hepatic and visceral adipose tissue 11βHSD1 expressions are markers of body weight loss after bariatric surgery

“…The considerable reduction in overall SAT tissue that comprises twothirds of total adipose tissue, together with the near 50% reduction in SAT 11bHSD1 expression 1 year after surgery, could significantly account for the downshift of serum and tissue cortisol levels. Accordingly with our data, in rats, a reduction in HPA basal activity after bariatric surgery has been recently reported, in contrast to the HPA activation elicited by food-restriction to achieve body weight loss (22). In this context, correlations found between total cortisol and ACTH with body weight, BMI and adipose tissue are consistent with the increase in food intake and body weight elicited by glucocorticoids in humans (23).…”

“…The literature concerning this issue is scarce and, again, controversial. Data obtained for nonhealthy women with obesity 1 year or 2 years after bariatric surgery are consistent with our results, but those including men and women with healthy obesity are not .…”

The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions

“…The study of eight participants who were subjected to DER for 2 years in a closed ecological space (Biosphere 2) also showed increased morning total cortisol ( 157 ). Interestingly, Grayson et al ( 158 ) reported that rodent weight loss induced by DER increased basal HPA axis activity, unlike the same level of weight loss induced by bariatric surgery. Cortisol is usually released in a circadian rhythm, being an important aspect of the circadian system.…”

MANAGEMENT OF ENDOCRINE DISEASE: Which metabolic procedure? Comparing outcomes in sleeve gastrectomy and Roux-en Y gastric bypass

“…Although these findings are important and help to shed light on the mechanisms of metabolic surgery, there is ample evidence that food restriction plays a lesser role than initially expected (69,70). In line with these findings are recent studies showing that the fibroblast growth factor, a hormone that is relevant for energy consumption and mitochondrial function and the hypothalamic-adrenal axis is very differently affected by metabolic surgery than very-low-calorie diets (71,72). Further supporting the role of hormonal changes after metabolic surgery is the fact that the LAGB is clearly inferior to both SG and RYGB regarding long-term weight loss and T2DM remission (73,74).…”