Leptin Receptors Are Not Required for Roux-en-Y Gastric Bypass Surgery to Normalize Energy and Glucose Homeostasis in Rats

Abstract

Sensitization to the adipokine leptin is a promising therapeutic strategy against obesity and its comorbidities and has been proposed to contribute to the lasting metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We formally tested this idea using Zucker fatty fa/fa rats as an established genetic model of obesity, glucose intolerance, and fatty liver due to leptin receptor deficiency. We show that the changes in body weight in these rats following RYGB largely overlaps with that of diet-induced obese Wistar rats with intact leptin receptors. Further, food intake and oral glucose tolerance were normalized in RYGB-treated Zucker fatty fa/fa rats to the levels of lean Zucker fatty fa/+ controls, in association with increased glucagon-like peptide 1 (GLP-1) and insulin release. In contrast, while fatty liver was also normalized in RYGB-treated Zucker fatty fa/fa rats, their circulating levels of the liver enzyme alanine aminotransferase (ALT) remained elevated at the level of obese Zucker fatty fa/fa controls. These findings suggest that the leptin system is not required for the normalization of energy and glucose homeostasis associated with RYGB, but that its potential contribution to the improvements in liver health postoperatively merits further investigation.

Gut peptides before and following Roux‐En‐Y gastric bypass: A systematic review and meta‐analysis

“…The reasoning for this is that a large number of studies solely evaluating leptin were retrieved and could, by themselves, be studied in a future meta-analysis. Because leptin signaling does not appear to be necessary for appetite suppression and weight loss after RYGB, 25,32,33 members of the research group decided not to have leptin as a main outcome in this paper. If data from multiple reports corresponded to the same study, only the study with the most information of the outcomes of interest was included.…”

Periphery-Brain Interactions and Leptin in the Regulation of Whole-Body Energy Metabolism

“…Hankir et al [1] revisited the premise that enhanced central leptin sensitivity contributes to the beneficial effects of RYGB on body weight status, glycemic control, and liver health. The researchers performed RYGB on Zucker fatty rats that developed overweight and obesity, glucose intolerance and fatty liver disease from functional mutation loss in the leptin receptor gene and diet-induced obese rats with intact leptin receptors.…”