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

• Main Authors: Mohammed K. Hankir, Laura Rotzinger, Arno Nordbeck, Caroline Corteville, Ulrich Dischinger, Juna-Lisa Knop, Annett Hoffmann, Christoph Otto, Florian Seyfried
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Nutrients
• Subjects: Roux-en-Y gastric bypass surgery; energy homeostasis; glucose homeostasis; fatty liver; leptin system; Zucker fatty <i>fa/fa</i> rats
• Online Access: https://www.mdpi.com/2072-6643/13/5/1544

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 <i>fa/fa</i> 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 <i>fa/fa</i> rats to the levels of lean Zucker fatty <i>fa/+</i> 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 <i>fa/fa</i> rats, their circulating levels of the liver enzyme alanine aminotransferase (ALT) remained elevated at the level of obese Zucker fatty <i>fa/fa</i> 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.