A Role for Oncostatin M in the Impairment of Glucose Homeostasis in Obesity.

Abstract

CONTEXT:

Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood.

OBJECTIVE:

The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice.

DESIGN:

28 patients with severe obesity were included and stratified into two groups: (1) glucose levels <100 mg/dL and (2) glucose levels >100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects.

RESULTS:

OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice.

CONCLUSIONS:

OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.

• Authors: Irene Piquer-Garcia, Laura Campderros, Siri D Taxerås, Aleix Gavaldà-Navarro, Rosario Pardo, María Vila, Silvia Pellitero, Eva Martínez, Jordi Tarascó, Pau Moreno, Joan Villarroya, Rubén Cereijo, Lorena González, Marjorie Reyes, Silvia Rodriguez-Fernández, Marta Vives-Pi, Carles Lerin, Carrie M Elks, Jacqueline M Stephens, Manel Puig-Domingo, Francesc Villarroya, Josep A Villena, David Sánchez-Infantes
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 105 Issue 3 (Mar 01 2020) ISSN: 1945-7197 [Electronic] United States
• PMID: 31606738 (Publication Type: Journal Article)
• Copyright: © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Glucose Transporter Type 4
• Receptors, Oncostatin M
• Oncostatin M
• Glucose

Topics

• Adipocytes (cytology)
• Adult
• Animals
• Female
• Glucose (metabolism)
• Glucose Transporter Type 4 (genetics)
• Homeostasis
• Humans
• Insulin Resistance
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Obesity (metabolism)
• Oncostatin M (physiology)
• Receptors, Oncostatin M (physiology)