Contribution of GPNMB protein on temporal control and hepatic glucose metabolism in mice subjected to a hyperlipidic diet

• Grant number: 23/08461-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Grantee: Eliz Maria de Oliveira Furtado
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism, AP.JP

Abstract

Circadian metabolism control involves both the central biological clock and peripheral clocks, such as the liver, which exhibit rhythmic physiological functions according to the phase of activity or rest. Such temporal regulation depends on the functioning of molecular components of the biological clock that involves a series of clock genes that act through positive and negative feedback loops. Animals submitted to hyperlipidic diets, present alteration in the expression of hepatic clock genes, which may lead to phase alteration in the rhythmic profile. Lifestyle changes, such as sedentary lifestyle and consumption of high-fat diets, contribute to metabolic disorders such as insulin resistance and type 2 diabetes mellitus (DM2) that may predispose to liver damage. In cases of DM2 and fatty liver disease, high GPNMB protein expression, which is positively correlated with higher BMI, is observed in rodents and humans. Therefore, we propose that the increase in hepatic GPNMB induced by hyperlipidic diet associated with fructose may affect glucose homeostasis and be associated with a dysregulation of hepatic temporal function. Thus, the hepatic glucose metabolism will be evaluated by ipGTT and ITT, as well as the response to insulin stimulation of components of the glycogenolysis pathway in mice carrying the mutated GPNMB protein in response to fructose-associated HFD. Complementarily, the temporal profile of clock genes in the liver will be evaluated.