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Effect of saturated fatty acids in the molecular mechanisms involved in the central control of feeding: immunomodulation and autophagy


Obesity is a public health problem that reached epidemic proportions in the last few years. The increased body fat storage due to impairment in energy balance is the determinant of obesity. The hypothalamus in the central nervous system (CNS) is the region responsible to coordinate and integrate peripheral signals as nutrients and hormones, regulating food intake and energy expenditure. The energy balance disruption prior to obesity onset is due to the inflammatory stimuli in the hypothalamus associated with the activation of TLR4 and ER stress. Studies have shown that disruption in autophagy, a cellular process responsible to the organelles and protein clearance can induce body weight gain, once hypothalamic homeostasis is impaired. Autophagy is responsible to the degradation of intracellular proteins, and disruption of this mechanism induces the overload of dysfunctional proteins and protein aggregate, leading to neurotoxicity. Recent studies have shown that animals submitted to DIO presented decreased expression of autophagy markers in hypothalamus which is important to exacerbate the inflammatory response via IKK/NFkB pathway. Thus, the aim of this study is to investigate the relationship between TLR4 activation and autophagy modulation in response to saturated fatty acids in the hypothalamus. The investigation of TLR4 activation and autophagy modulation in neuronal cell lines and in murine model submitted to DIO. The first step of this study will be the investigation of macroautophagy and chaperone mediated autophagy (CMA) in different time exposition in response to HFD. The second step of this investigation will be to unveil the connection between TLR4 activation and autophagy pathway. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PORTOVEDO, M.; REGINATO, A.; MIYAMOTO, J. E.; SIMINO, L. A.; HAKIM, M. P.; CAMPANA, M.; LEAL, R. F.; IGNACIO-SOUZA, L. M.; TORSONI, M. A.; MAGNAN, C.; et al. Lipid excess affects chaperone-mediated autophagy in hypothalamus. Biochimie, v. 176, p. 110-116, . (14/11751-0, 13/10911-0)

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