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CD1 protein is involved in diet-induced hypothalamic inflammation in obesity

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Author(s):
Bruna Bombassaro
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Licio Augusto Velloso; Gabriel Forato Anhê; Liana Maria Cardoso Verinaud; Alexandre Alarcon Steiner; Fernando Abdulkader
Advisor: Licio Augusto Velloso
Abstract

Obesity is the main risk factor for many comorbidities and its prevalence is rising to astounding numbers. The activation of a subclinic and chronic inflammatory process in the hypothalamus has been shown to be the trigger event leading to several comorbidities, such as insulin resistence and diabetes. This process occurs due to a complex interaction between genetic and envirolmental factors. The consumptions of saturated fatty acid rich diets is one of the most important envirolmental factors, leading to inflammation due to activation of the innate immune receptor, TLR4. The role of innate immune response in the hypothalamic inflammation has been extensively studied. However, the putative role of the adaptive immune response in this scenario is still unknown. In neurodegenative diseases, the inflammation is responsible for the recruitment and activation of T lymphocytes to the brain, which contributes to the emergence of many syptoms of the diseases. As we know that fatty acids trigger an infammatory immune response that disrupts hypothalamic control of food intake and energy homeostases, we hypothesized that CD1, a lipid-presenting protein to lymphocytes, would play a central role in the hypothalamic immune response. In this work, we show that as early as one day of high fat diet, the CD1 expression is higher in the hypothalamus of mice and the distribution in this tissue is also disturbed. The deacrease in CD1 expression leads to improvement of glucose tolerance e reduced weight gain; wheras the increase of CD1 signaling exacerbates the obese phenotype. Bioinformatics analyses showed that the hypothalamic expression of CD1 correlates with other celular mechanisms involved in the pathophysiology of obesity. Therefore, CD1 seems to have a pivotal role in hypothalamic inflammation due to saturated fatty acids consumption (AU)

FAPESP's process: 13/25415-9 - Evaluation Of Adaptive Immune Response in Inflammation of the Hypothalamus in Obesity
Grantee:Bruna Bombassaro
Support Opportunities: Scholarships in Brazil - Doctorate