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Differential Responses to Sigma-1 or Sigma-2 Receptor Ablation in Adiposity, Fat Oxidation, and Sexual Dimorphism.
Li, Jing; Félix-Soriano, Elisa; Wright, Katherine R; Shen, Hongtao; Baer, Lisa A; Stanford, Kristin I; Guo, Lian-Wang.
  • Li J; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Félix-Soriano E; Department of Physiology & Cell Biology, College of Medicine, Wexner Medical Center, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Wright KR; Department of Physiology & Cell Biology, College of Medicine, Wexner Medical Center, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Shen H; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Baer LA; Department of Physiology & Cell Biology, College of Medicine, Wexner Medical Center, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Stanford KI; Department of Physiology & Cell Biology, College of Medicine, Wexner Medical Center, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Guo LW; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Int J Mol Sci ; 23(18)2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2039873
ABSTRACT
Obesity is increasing at epidemic rates across the US and worldwide, as are its co-morbidities, including type-2 diabetes and cardiovascular disease. Thus, targeted interventions to reduce the prevalence of obesity are of the utmost importance. The sigma-1 receptor (S1R) and sigma-2 receptor (S2R; encoded by Tmem97) belong to the same class of drug-binding sites, yet they are genetically distinct. There are multiple ongoing clinical trials focused on sigma receptors, targeting diseases ranging from Alzheimer's disease through chronic pain to COVID-19. However, little is known regarding their gene-specific role in obesity. In this study, we measured body composition, used a comprehensive laboratory-animal monitoring system, and determined the glucose and insulin tolerance in mice fed a high-fat diet. Compared to Sigmar1+/+ mice of the same sex, the male and female Sigmar1-/- mice had lower fat mass (17% and 12% lower, respectively), and elevated lean mass (16% and 10% higher, respectively), but S1R ablation had no effect on their metabolism. The male Tmem97-/- mice exhibited 7% lower fat mass, 8% higher lean mass, increased volumes of O2 and CO2, a decreased respiratory exchange ratio indicating elevated fatty-acid oxidation, and improved insulin tolerance, compared to the male Tmem97+/+ mice. There were no changes in any of these parameters in the female Tmem97-/- mice. Together, these data indicate that the S1R ablation in male and female mice or the S2R ablation in male mice protects against diet-induced adiposity, and that S2R ablation, but not S1R deletion, improves insulin tolerance and enhances fatty-acid oxidation in male mice. Further mechanistic investigations may lead to translational strategies to target differential S1R/S2R regulations and sexual dimorphism for precision treatments of obesity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, sigma / Insulins / COVID-19 Type of study: Observational study / Prognostic study Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Ijms231810846

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, sigma / Insulins / COVID-19 Type of study: Observational study / Prognostic study Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Ijms231810846