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Characterization of mechanisms involved on early regulation of POMC neurons in response to saturated fatty acids

Grant number: 16/23271-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 27, 2017
Effective date (End): September 26, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Licio Augusto Velloso
Grantee:Daniela Soares Razolli
Supervisor abroad: Florian Tobias Merkle
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: University of Cambridge, England  
Associated to the scholarship:14/00742-0 - Characterization of rapid POMC regulation mechanisms involved in high-fat diet response, BP.PD

Abstract

The development of obesity is due to association between genetic, metabolic and hormones factors. As consequence it's contribute to insulin resistance, cardiovascular diseases, hypertension, dyslipidemia and certain types of cancer. Obesity affects more than 500 million human worldwide which represent one of the most clinical-epidemiological phenomenon currently. In the past ten years studies have shown that saturated fat acids act through specific receptors, as such as TLR4, activating cellular signaling pathways involved with the expression of mediators of inflammation, endoplasmic reticulum stress and apoptosis of hypothalamic neurons that participate of the food intake control and energy expenditure. Furthermore, worsen the gut-brain signaling and gastrointestinal peptides secretion. The consumption of a diet rich in saturated fat acids promotes hypothalamic inflammation and disruption of anorexigenic signaling, especially in POMC neurons, favoring weight gain. Here, we employed obese prone (OP) and obese resistant (OR) mice to characterize the mechanism involved in saturated fatty acid of POMC neuron function. We have concluded experiments in mice that supports the hypothesis that palmitate can modulate the expression of enzymes involved in the synthesis of alpha-MSH and beta-endorphin. Recently Dr. Florian Merkle. efficiently generated functional hypothalamic neurons from human pluripotent stem cells (hPSCs). In collaboration with Dr. Merkle we would like to test our main findings from rodents experiments in human hPSCs POMC cells, as part of a BEPE-FAPESP project. We believe that with this set of experiments we will be able to elevate the quality of this research in a significant level. (AU)

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