Role of microglial cells in the high-fat diet-induced hypothalamic inflammation

• Grant number: 17/22511-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 01, 2018
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Eliana Pereira de Araujo
• Grantee: Natália Ferreira Mendes
• Supervisor: Young-Bum Kim
• Host Institution: Faculdade de Enfermagem. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 16/17810-3 - Evaluation of TGF-b1 function in the hypothalamus of animals with obesity and diabetes induced by high-fat diet, BP.DR

Abstract

Emerging data demonstrate that microglial inflammatory signaling plays a pivotal role in the development of obesity induced-hypothalamic inflammation. In the early stages of hypothalamic inflammation, cells from microglia recognize the excess of saturated fatty acids (SFAs) from the diet and activate an important inflammatory response. Due to fenestrated nature of the blood-brain barrier (BBB) surrounding the mediobasal hypothalamus, bone-marrow-derived myeloid cells can cross BBB in response to this excessive consumption of SFAs, magnifying hypothalamic inflammation. However, a major limitation in understanding SFAs-induced metabolic dysfunction is a lack of knowledge of direct involvement of hypothalamic microglial cells or bone marrow-derived myeloid cells on the development of hypothalamic inflammation (at the early stage during over-nutrition). To address this, Aim 1 will determine whether modulation of hypothalamic microglial activity can affect hypothalamic inflammation and energy metabolism. Aim 2 will determine the contribution of microglial cells or bone marrow-derived myeloid cells in regulating SFAs-induced hypothalamic inflammation. To accomplish these aims, we will use state-of-the-art technologies, including DREADD (designer receptors exclusively activated by designer drugs) to directly modulate hypothalamic microglia cells, CX3CR1-Cre and CD169-Cre mice to test cellular mechanisms of fat-induced hypothalamic inflammation in an in vivo context. These studies provide a unique opportunity to establish a new paradigm in which microglial cell or bone marrow-derived myeloid cells is a key determinant of fat-induced metabolic disorders, and may offer a novel target for the treatment of obesity and its co-morbidities.

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)

MENDES, NATALIA F.; KIM, YOUNG-BUM; VELLOSO, LICIO A.; ARAUJO, ELIANA P.. Hypothalamic Microglial Activation in Obesity: A Mini-Review. FRONTIERS IN NEUROSCIENCE, v. 12, NOV 15 2018. (17/22511-8, 13/07607-8, 17/02983-2, 16/17810-3)

MENDES, NATALIA; ZANESCO, ARIANE; AGUIAR, CRISTHIANE; RODRIGUES-LUIZ, GABRIELA F.; SILVA, DAYANA; CAMPOS, JONATHAN; CAMARA, NIELS OLSEN SARAIVA; MORAES-VIEIRA, PEDRO; ARAUJO, ELIANA; VELLOSO, LICIO A.. CXCR3-expressing myeloid cells recruited to the hypothalamus protect against diet-induced body mass gain and metabolic dysfunction. eLIFE, v. 13, p. 27-pg., 2024-11-13. (21/00443-6, 17/22511-8)