The 2020 ESPEN Arvid Wretlind lecture: Metabolic response in bariatric surgery - Mechanisms and clinical implications

Abstract

Background & aims: Owing to the "obesity-pandemic", an increasing number of individuals are in need of treatment for obesity and obesity-related disorders. For patients with severe disease, results with conventional treatment modalities such as diet regimens, physical activity, and pharmacologic agents most often lack satisfactory efficacy and/or sustainability. In contrast, bariatric surgery has been demonstrated to be associated with marked, long-term weight loss as well as resolution or improvement of co-morbid disease, in particular metabolic aberrations such as insulin resistance and type 2 diabetes. The underlying mechanisms for the effects of surgery-induced weight loss on such morbidity are incompletely understood.

Methods: This article gives an updated overview of some aspects on the mechanisms involved in the improvement in metabolism in obese individuals submitted to surgery-induced weight loss. Patients undergoing Roux en-Y Gastric Bypass (RYGB) were studied before and at various times after the operation. Weight, body composition with determination of distribution of adipose tissue (DEXA), and insulin sensitivity (hyperinsulinemic clamp) was determined. In vitro; lipolytic activity and adipose morphology (fat cell size) was assessed.

Results: Low calorie intake, rerouting of nutrients as well as loss of fat mass are all associated with improved insulin sensitivity after RYGB. In obese individuals, an increase in lipolytic activity in visceral adipose tissue might contribute to the association with cardiometabolic disease. However, selective reduction (omentectomy) seems not to improve insulin sensitivity or cardiometabolic risk. Adipose hyperplasia (many small cells) might be protective against metabolic abnormalities compared to hypertrophy (large cells). Preoperative fat cell size is related to improvement in insulin sensitivity after RYGB. Two years after weight loss, a change in adipose morphology to a more metabolically benign phenotype (remodeling) is seen, with a reduction of fat cell size which is correlated to the improvement in insulin sensitivity. Patients with weight regain 5 years after RYGB, still display a more benign metabolic profile compared to weight-matched controls.

Conclusions: Several factors contribute to the improvements in insulin sensitivity and cardiometabolic disease after surgery-induced weight loss, including low calorie intake rerouting of nutrients and loss of adipose tissue mass. Increased lipolytic activity in visceral adipose tissue as well as adipose hypertrophy relates to increased metabolic risk. RYGB-induced weight loss is associated with redistribution of adipose tissue as well as remodeling of fat cells to a more benign profile. Reduction of fat cell size might be a possible target to improve insulin sensitivity in patients with obesity in the future.

Keywords: Bariatric surgery; Lipolysis; Obesity; Subcutaneous adipose tissue; Visceral adipose tissue; Weight regain.