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Effect of palmitate treatment in PC 1/3 expression in a hypothalamic cell lineage

Grant number: 19/00330-7
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2019
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Licio Augusto Velloso
Grantee:Ariane Maria Zanesco
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity is a worldwide public health problem frequently associated to comorbidities like type 2 diabetes, systemic arterial hypertension and cardiovascular complications. Food intake and energy expenditure are highly regulated by first-order neuronal populations located in the hypothalamic arcuate nucleus: the POMC e NPY/AgPR neurons. The released prohormone POMC is cleaved by specific proteins, among them the PC 1/3, resulting in inhibitory control of food intake and increase in energy expenditure. The increased consumption of palmitate, a saturated fatty acid found abundantly in ultra-processed foods, has been associated, in preclinical studies, to hypothalamic damage that leads to neuronal dysfunction and cell death. The main outcome seems to be an imbalance in energy homeostasis control due to damage in POMC neurons. Palmitate may interfere with the activation of some signaling pathways, including the pathway that activates the cyclic AMP response-element-binding protein (CREB), a nuclear protein which when phosphorylated by PKA and / or CaCaMK II proteins exerts transcription promoter effects. For identification of the possible modifications on these pathways, we will run gene and protein expression analysis of CaCaMK II, PKA, CREB and PC 1/3 proteins, after palmitate exposure in the hypothalamic cell lineage mHypoA 2/29 (CLU189). Inhibition assays will be performed to evaluate if CaCaMK II, PKA, CREB proteins have a regulatory effect on PC 1/3 gene and protein expression. Therefore, this work aims to elucidate if palmitate can induce alterations in these signaling pathways and establish if these proteins are involved in the cleavage process of the prohormone POMC by the enzyme PC 1/3.