The effects of physical exercise on IP3 in the liver of obese mice

• Grant number: 19/11338-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2019
• End date: October 31, 2020
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Rodrigo Pauli
• Grantee: Rafael Calais Gaspar
• Supervisor: Gerald Shulman
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: Yale School of Medicine (YSM), United States
• Associated to the scholarship: 17/20542-3 - Role of physical exercise in regulation of Notch1 protein in obese mice: effects on hepatic lipogenesis and gluconeogenesis, BP.DR

Abstract

In hepatocytes, the calcium (Ca+) concentrations play an important role in the cellular function. In this setting, studies have demonstrated that calcium plays an important role in the development of Non-alcoholic fatty liver disease (NAFLD). However, few therapies are efficient to treat the lipid accumulation in the liver. Thus, the IP3Rs are impotent intracellular regulators of calcium fluxes. Therefore, diabetic mice have increased IP3R-I activity suggesting the role IP3R-I in lipids metabolic liver. In this grant we will test the chronic excercise training will result in increases in plasma glucagon concentrations which in turn will result in increases hepatic mitochondrial oxidation rates by signaling through the InsP3R-I receptor. Next we will perform chronic exercise training in HFD IP3R-I KO mice in order to determine whether liver calcium signaling is required to mediate the effect of exercise to improve hepatic and/or whole-body insulin sensitivity with exercise training.

Scientific publications

(4)

(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)

GASPAR, RAFAEL C.; LYU, KUN; HUBBARD, BRANDON T.; LEITNER, BROOKS; LUUKKONEN, PANU; HIRABARA, SANDRO; SAKUMA, IKKI; NASIRI, ALI; ZHANG, DONGYAN; KAHN, MARIO; et al. Lower Plasma Membrane Sn-1,2-Diacylglycerol Content and PKCepsilon/theta Activity Explain the Athlete's Paradox. Diabetes, v. 70, p. 3-pg., 2021-06-01. (19/11338-9, 17/20542-3)

GASPAR, RAFAEL C.; PAULI, JOSE R.; SHULMAN, I, GERALD; MUNOZ, VITOR R.. An update on brown adipose tissue biology: a discussion of recent findings. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 320, n. 3, p. E488-E495, MAR 2021. (19/00227-1, 19/11338-9, 18/07568-6, 18/20872-6)

GASPAR, RAFAEL C.; MUNOZ, VITOR; NAKANDAKARI, SUSANA C.; CRISOL, BARBARA M.; VIEIRA, RENAN F. L.; CONCEICAO, LUCIANA R.; SILVA, ADELINO; CINTRA, DENNYS E.; MOURA, LEANDRO P.; ROPELLE, EDUARDO R.; et al. Physical Exercise Decreases Notch1 Activation and Reduces the Gluconeogenesis in Liver of Obese Mice. Diabetes, v. 69, p. 2-pg., 2020-06-01. (19/11338-9, 17/20542-3)

GASPAR, RAFAEL C.; LYU, KUN; HUBBARD, BRANDON T.; LEITNER, BROOKS P.; LUUKKONEN, PANU K.; HIRABARA, SANDRO M.; SAKUMA, IKKI; NASIRI, ALI; ZHANG, DONGYAN; KAHN, MARIO; et al. Distinct subcellular localisation of intramyocellular lipids and reduced PKC epsilon/PKC theta activity preserve muscle insulin sensitivity in exercise-trained mice. Diabetologia, v. 66, n. 3, p. 12-pg., 2022-12-01. (19/11338-9, 17/20542-3, 20/13443-1)