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Apoptosis in hypothalamic neurons from rats fed high-fat diet

Juliana Contin Moraes
Total Authors: 1
Document type: Doctoral Thesis
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Anibal Eugenio Vercesi; Eliane Beraldi Ribeiro; Francesco Langone; Silvana Bordin
Advisor: Licio Augusto Velloso

Obesity and diabetes have reached epidemic proportions in several regions of the world. General changes in life-style, including consumption of fat-rich diets, are amongst the most important factors leading to an unprecedented increase in the prevalence of these diseases. The complete characterization of the pathophysiological mechanisms leading to obesity and diabetes may disclose potential targets for the development of specific drugs and development of better prophylactic approaches. Recent work has shown that the consumption of a fat-rich diet for 16 weeks leads to the increased expression of pro-inflammatory cytokines in the hypothalamus, which is accompanied by an apparent reduction in the numbers of neurons in this region. Because many of these cytokines can activate apoptotic pathways we decided to investigate the presence of apoptosis in neurons from rats fed on high-fat diet. Using real-time PCR, TUNEL, immunoblot, immunohistochemistry and transmission electron microscopy we observed increased apoptosis of neurons of the hypothalamus. The subpopulations preferentially affected depend on genetic background. Thus, in a strain genetically protected from obesity, apoptosis affects both, orexigenic and anorexigenic neurons, while in an obesity-prone strain, the anorexigenic neurons are preferentially affected. In addition, we observed that the presence of an intact TLR4 expression protects against apoptosis, suggesting that this receptor of the innate immune system plays a dual role, participating in the activation of an inflammatory response and protecting against further neuronal damage. We believe the present data will contribute to unveil some the pathophysiological mechanisms involved in the development of obesity and the roles played by nutritional and immunological factors in this context (AU)