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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Obesity
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1448107

Loss of Sult1a1 reduces body weight and increases browning of white adipose tissue Authors

Provisionally accepted
  • 1 Max Planck Institute of Psychiatry (MPI), Munich, Germany
  • 2 Université Claude Bernard Lyon 1, Lyon, Rhône-Alpes, France
  • 3 Chair of Molecular Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany
  • 4 Maven Health, Lausanne, Switzerland
  • 5 PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch, France
  • 6 Centre Hospitalier Universitaire (CHU) de Saint-Étienne, Saint-Etienne, France
  • 7 Nestlé Research Center, Lausanne, Vaud, Switzerland

The final, formatted version of the article will be published soon.

    Background & Objectives: Overweight and obesity affects millions of individuals worldwide and consequently represents a major public health concern. Individuals living with overweight and obesity have difficulty maintaining a low body weight due to known physiological mechanisms which prevent further weight loss and drive weight regain. In contrast, mechanisms which promote low body weight maintenance receive less attention and are largely unknown. To uncover these intrinsic mechanisms, we investigated a human cohort of constitutionally thin (CT) individuals which maintain a low body weight and are resistant to weight gain despite exposure to an obesogenic environment. Methods: To identify novel genes that contribute to low body weight maintenance, we performed transcriptomics on adipose tissue biopsies collected from CT and normal body weight (NBW) individuals and identified sulfotransferase 1A1 (SULT1A1) as a target for further investigation in mice. Sult1a1 knockout (KO) mice were fed a standard diet to assess the impact of Sult1a1 deletion on metabolic traits. To determine if high-fat feeding recapitulated the CT weight gain resistance phenotype, Sult1a1 KO mice were fed a high-fat diet for 13-weeks. A subset of wild-type and Sult1a1 KO mice from the standard diet were further analyzed for characterization of adipose tissue respiratory capacity. Results: In comparison to NBW controls, adipose tissue from CT individuals expresses less SULT1A1. Sult1a1 KO mice weigh 10% less at the end of the study period and on a high-fat diet, Sult1a1 KO mice tended to gain less weight and had reduced fat mass at 14-weeks of age. These changes were associated with reduced fasting insulin and lessened adipose tissue inflammation and fibrosis. Subcutaneous adipose tissue from Sult1a1 KO mice on a standard chow diet had elevated leak respiration, uncoupling protein 1 (UCP1) expression and increased expression of a mitochondrial marker, VDAC, associating Sult1a1 deletion to adipose tissue browning. Conclusions: Our results associate Sult1a1 deletion with a tendency for lower body weight through remodeling of white adipose tissue towards a brown phenotype. The presence of UCP1, the expression of an additional mitochondrial protein and increased respiratory capacity suggest browning of the subcutaneous adipose tissue depot of Sult1a1 KO mice.

    Keywords: Sulfotransferase 1A1, white adipose tissue, Browning, leanness, Obesity

    Received: 12 Jun 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Springer, Meugnier, Schnabl, Hof, Champy, Sorg, Petit-Demoulière, GERMAIN, Estour, Vidal, Klingenspor and Hager. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Margherita Springer, Max Planck Institute of Psychiatry (MPI), Munich, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.