Effect of palmitate treatment in pc1/3 expression in a hypothalamic cell lineage

• Grant number: 19/00330-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2019
• Effective date (End): April 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Ariane Maria Zanesco
• Host 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. (AU)

Scientific publications

(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)

MENDES, NATALIA FERREIRA; JARA, CARLOS POBLETE; ZANESCO, ARIANE MARIA; DE ARAUJO, ELIANA PEREIRA. Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet-Induced Inflammation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 5, MAR 2021. (19/00330-7, 17/22511-8, 16/17810-3, 13/07607-8)

ZANESCO, ARIANE MARIA; MENDES, NATALIA F.; ENGEL, DAIANE F.; GASPAR, RODRIGO S.; SIDARTA-OLIVEIRA, DAVI; DONATO, JOSE; VELLOSO, LICIO A.. Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2. CELLS, v. 11, n. 13, p. 20-pg., 2022-07-01. (13/07607-8, 19/00330-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ZANESCO, Ariane Maria. The hypothalamic CREB transcription factor is regulated by palmitate and hyperlipidic diet. 2021. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.