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Effect of interleukin 17 in the hypothalamic regulation of energy homeostasis

Grant number: 14/24362-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Licio Augusto Velloso
Grantee:Guilherme Augusto da Silva Nogueira
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Obesity results from the interaction between genetic, metabolic, hormonal and environmental factors. Once established, promotes the development of insulin resistance, cardiovascular disease, hypertension, dyslipidemia and some cancers, impacting on quality of life and mortality rates of the population. By providing high spending on public health and affecting approximately 300 million people worldwide, obesity is a major clinical and epidemiological phenomena of recent times. Recent studies have shown that interleukin 17 (IL-17) is capable of modulating the expression of leptin, predisposing mice to obesity. An important site of action of cytokines is the mucosal barrier of the gastrointestinal tract by stimulating the production of adhesion and anti-microbial molecules involved in the barrier integrity. Changes in the expression of this interleukin may lead to imbalanced homeostasis of resident intestinal microbiota, favoring increased permeability of this tissue and translocation of bacterial lipopolysaccharide and thus, metabolic endotoxemia associated with increased inflammatory tone, body weight gain and resistance to insulin. A study conducted at the Laboratory of Cell Signaling showed that the increased expression of mRNA of IL-17 in mice gut reflected in an increased plasmatic cytokine which plays an important effect on insulin secretion, similarly to the incritin hormones. Furthermore, also a pilot study conducted in our laboratory showed that injection of IL-17 intraperitoneally in fasted mice C57BL/6 increased the expression of the POMC hypothalamic neuropeptide, suggesting that IL-17 may be involved in the modulation of hunger and hypothalamic energy homeostasis, but to the best of our knowledge, the mechanisms involved in this process are unclear. Outbred animals prone and obesity-resistant will be separated into groups that receive standard or high fat diet. The hypothalamus of animals will be extracted after acute stimulation of IL-17 in a time-course. Through real-time PCR, immunoblot and indirect immunofluorescence analysis by confocal microscopy assays we will analyze the modulation of neurotransmitter expression mediated by this cytokine. (AU)