Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery

Version 1 : Received: 8 February 2021 / Approved: 9 February 2021 / Online: 9 February 2021 (16:57:48 CET)
Version 2 : Received: 11 February 2021 / Approved: 12 February 2021 / Online: 12 February 2021 (13:11:41 CET)

How to cite: Hankir, M.K.; Rotzinger, L.; Nordbeck, A.; Corteville, C.; Hoffmann, A.; Otto, C.; Seyfried, F. Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery. Preprints 2021, 2021020243 (doi: 10.20944/preprints202102.0243.v1). Hankir, M.K.; Rotzinger, L.; Nordbeck, A.; Corteville, C.; Hoffmann, A.; Otto, C.; Seyfried, F. Intact Leptin Receptor Signalling is not Required for the Sustained Weight Loss and Appetite Suppression Induced by Roux-en-Y Gastric Bypass Surgery. Preprints 2021, 2021020243 (doi: 10.20944/preprints202102.0243.v1).

Abstract

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of endogenous leptin action. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Keywords

Roux-en-Y gastric bypass surgery; Weight loss; Food intake; Oral glucose tolerance; Leptin; Leptin receptors; Zucker Fatty fa/fa rats

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