iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents

Author(s)

Katashima, Carlos Kiyoshi ; Rodrigues Silva, Vagner Ramon ; Lenhare, Luciene ; Marin, Rodrigo Miguel ; Campello Carvalheira, Jose Barreto

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, AUG 23 2017.
• Web of Science Citations: 5

Abstract

Inducible nitric oxide (iNOS)-mediated S-nitrosation of the metabolic signaling pathway has emerged as a post-translational modification that triggers insulin resistance in obesity and aging. However, the effects of S-nitrosation in controlling energy homeostasis are unknown. Thus, in the present study we aimed to evaluate the effects of S-nitrosation in insulin signaling pathway in the hypothalamus of rodents. Herein, we demonstrated that the intracerebroventricular infusion of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) promoted hypothalamic insulin signaling resistance and replicated the food intake pattern of obese individuals. Indeed, obesity induced S-nitrosation of hypothalamic IR and Akt, whereas inhibition of iNOS or S-nitrosation of insulin signaling pathway protected against hypothalamic insulin resistance and normalized energy homeostasis. Overall, these findings indicated that S-nitrosation of insulin signaling pathway is required to sustain hypothalamic insulin resistance in obesity. (AU)

• FAPESP's process: 10/19503-4 - S-nitrosation of proteins involved in insulin and leptin signaling pathways in the hypothalamus of obese rodents: a novel mechanism involved in obesity genesis
• Grantee: José Barreto Campello Carvalheira
• Support Opportunities: Regular Research Grants