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Effects of obesity on hypothalamic glucose metabolism: role of lactato-dehydrogenase A and B enzymes

Grant number: 19/14428-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Eliane Beraldi Ribeiro
Grantee:Pedro Norton Gonçalves Dias
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The hypothalamic metabolism of glucose plays an important role in the central control of glycemia and food intake, aspects that are dysregulated in obesity and diabetes. In astrocytes, glucose metabolism generates pyruvate, which is converted to lactate by the enzyme lactate dehydrogenase A (LDH-A). The lactate is then transferred to neurons where it is reconverted to pyruvate by the enzyme LDH-B. The present project aims to evaluate whether the prolonged consumption of a high-fat saturated diet affects the mechanisms involved in hypothalamic glucose utilization .For this, 2 months-old Swiss mice will be fed for 12 weeks with either a control balanced diet or a hyperlipidic diet enriched with lard. Body mass and food intake will be measured once a week. At the end of the 12 weeks, the animals will receive an intraperitoneal injection of pyruvate and euthanized 1 hour later. The retroperitoneal, epididimal and mesenteric fat depots will me dissected and weighed. The hypothalami will be harvested and processed for determination of LDH-A and LDH-B protein levels by Western blot. Blood glucose levels will be measured.