This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: This research received grants from the Swiss National Science Foundation (Grant no. Received: FebruAccepted: ApPublished: August 11, 2021Ĭopyright: © 2021 Saponara et al. PLoS ONE 16(8):Įditor: Clemens Fürnsinn, Medical University of Vienna, AUSTRIA (2021) Single or combined ablation of peripheral serotonin and p21 limit adipose tissue expansion and metabolic alterations in early adulthood in mice fed a normocaloric diet. Our results suggest that serotonin and p21 act as a central molecular determinant of weight gain and associated metabolic alterations, and highlights the potential of targeting these molecules as a pharmacologic approach to prevent the development of obesity.Ĭitation: Saponara E, Chen R, Reding T, Zuellig R, Henstridge DC, Graf R, et al. Single or double ablation of Tph1 and p21 were equally effective in preventing adipocyte expansion and systemic perturbation of glucose metabolism, upon both normocaloric and hypercaloric diets. Mechanistically, we discovered that Tph1 inactivation resulted in down-regulation of cyclin-dependent kinase inhibitor p21 Waf1/Cip1 expression. Genetic inactivation of Tph1 was sufficient to limit adipose tissue expansion and associated metabolic alterations.

At the molecular level, this was associated with an increase in adipose tissue tryptophan hydroxylase 1 (Tph1) transcripts, the key enzyme responsible for the synthesis of peripheral serotonin.

We demonstrated that normal physiological weight gain was accompanied by an increase in adipose tissue mass and the presence of cellular and metabolic signatures typically found during obesity, including adipocyte hypertrophy, macrophage recruitment into visceral fat and perturbed glucose metabolism. In addition, we used three different genetic models to identify molecular factors that promote physiological weight gain during normocaloric and hypercaloric diets. Here we investigated both adipose tissue-specific and systemic events that underlie the physiological weight gain occurring during early adulthood in mice fed a normocaloric diet. Identifying the fundamental molecular factors that drive weight gain even in the absence of hypercaloric food intake, is crucial to enable development of novel treatments for the global pandemic of obesity.

Ablation and weight gain 2017