Hepatic bioenergetics and redox signaling in obesity murine model: integrative analysis of nutritional, hormonal, and inflammatory stimuli

• Grant number: 15/25862-0
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): June 01, 2016
• Effective date (End): January 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal researcher: Alicia Juliana Kowaltowski
• Grantee: Pâmela Aiako Hypólito Brito Kakimoto
• Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Increased production of intracellular oxidants due to nutrient overloading from diet has been linked to the development of metabolic diseases such as Nonalcoholic Fatty Liver Disease (NAFLD) and diabetes type 2. The inability of the adipose tissue to handle excess lipids can result in increased efflux of Non-Esterified Fatty Acids (NEFAs) and release of proinflammatory cytokines and adipokines that may result in ectopic fat deposition in the liver, muscle and heart. Mitochondrial lipid metabolism, when compared to carbohydrates, displays lower bioenergetic efficiency and increased production of reactive oxygen species. These functions, although fundamental for energy homeostasis and cellular redox signaling, may be involved in the development and progression of metabolic diseases. Oxidants, when exceeding cellular capacity to control and remove, may impair insulin signaling at both the level of the receptor and downstream, leading to resistance to its action. The cellular redox state is critical in the control of mitochondrial function, but, in addition, the activity of many metabolic enzymes and signaling processes is susceptible to oxidative modification. Consequently, understanding the actions of reactive species in metabolic control is important for uncovering the pathophysiological mechanisms of diet-associated metabolic diseases. In this project, we sought to evaluate the effects of obesity on the bioenergetic profile of murine hepatocytes, correlating to possible changes in the profile of redox signaling and insulin signaling. (AU)

Scientific publications

(7)

(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)

KAKIMOTO, PAMELA A.; SERNA, JULIAN DAVID C.; RAMOS, VITOR DE MIRANDA; ZORZANO, ANTONIO; KOWALTOWSKI, ALICIA J. Increased glycolysis is an early consequence of palmitate lipotoxicity mediated by redox signaling. REDOX BIOLOGY, v. 45, SEP 2021. Web of Science Citations: 0.

RAMOS, VITOR DE MIRANDA; KOWALTOWSKI, ALICIA J.; KAKIMOTO, PAMELA A. Autophagy in Hepatic Steatosis: A Structured Review. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, APR 15 2021. Web of Science Citations: 0.

CHAUSSE, BRUNO; KAKIMOTO, PAMELA A.; KANN, OLIVER. Microglia and lipids: how metabolism controls brain innate immunity. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 112, p. 137-144, APR 2021. Web of Science Citations: 3.

CERQUEIRA, FERNANDA M.; VON STOCKUM, SOPHIA; GIACOMELLO, MARTA; GOLIAND, INNA; KAKIMOTO, PAMELA; MARCHESAN, ELENA; DE STEFANI, DIEGO; KOWALTOWSKI, ALICIA J.; ZIVIANI, ELENA; SHIRIHAI, ORIAN S. A new target for an old DUB: UCH-L1 regulates mitofusin-2 levels, altering mitochondrial morphology, function and calcium uptake. REDOX BIOLOGY, v. 37, OCT 2020. Web of Science Citations: 0.

CHAUSSE, BRUNO; KAKIMOTO, PAMELA A.; CALDEIRA-DA-SILVA, CAMILLE C.; CHAVES-FILHO, ADRIANO B.; YOSHINAGA, MARCOS Y.; DA SILVA, RAILMARA PEREIRA; MIYAMOTO, SAYURI; KOWALTOWSKI, ALICIA J. Distinct metabolic patterns during microglial remodeling by oleate and palmitate. BIOSCIENCE REPORTS, v. 39, n. 4 APR 30 2019. Web of Science Citations: 0.

KAKIMOTO, PAMELA A.; CHAUSSE, BRUNO; CALDEIRA DA SILVA, CAMILLE C.; DONATO JUNIOR, JOSE PRIME; KOWALTOWSKI, ALICIA J. Resilient hepatic mitochondria! function and lack of iNOS dependence in diet-induced insulin resistance. PLoS One, v. 14, n. 2 FEB 4 2019. Web of Science Citations: 1.

ALSABEEH, NOUR; CHAUSSE, BRUNO; KAKIMOTO, PAMELA A.; KOWALTOWSKI, ALICIA J.; SHIRIHAI, ORIAN. Cell culture models of fatty acid overload: Problems and solutions. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1863, n. 2, p. 143-151, FEB 2018. Web of Science Citations: 10.