Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

Author(s):Show less -

de-Lima-Junior, Jose C. ^{[1, 2]} ; Souza, Gabriela F. ^{[1, 2]} ; Moura-Assis, Alexandre ^{[1, 2]} ; Gaspar, Rodrigo S. ^{[2, 3]} ; Gaspar, Joana M. ^{[1, 2]} ; Rocha, Andrea L. ^[4] ; Ferrucci, Danilo L. ^{[5, 6]} ; Lima, Tanes I. ^{[4, 2]} ; Victorio, Sheila C. ^{[1, 2]} ; Bonfante, Ivan L. P. ^[7] ; Cavaglieri, Claudia R. ^[7] ; Pareja, Jose C. ^[8] ; Brunetto, Sergio Q. ^[9] ; Ramos, Celso D. ^{[2, 10]} ; Geloneze, Bruno ^{[2, 8]} ; Mori, Marcelo A. ^[4] ; Silveira, Leonardo R. ^{[4, 2]} ; Segundo, Gesmar R. S. ^[11] ; Ropelle, Eduardo R. ^{[2, 3]} ; Velloso, Licio A. ^{[1, 2]}

Affiliation:Show less -

^[1] Univ Estadual Campinas, Dept Internal Med, Lab Cell Signaling, BR-13084970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Obes & Comorbid Res Ctr, BR-13084970 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Sch Appl Sci, CEPECE Res Ctr Sport Sci, Limeira, SP - Brazil

^[4] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil

^[5] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, BR-13083970 Campinas, SP - Brazil

^[6] Natl Inst Photon Appl Cell Biol INFABiC, Campinas, SP - Brazil

^[7] Univ Estadual Campinas, Lab Exercise Physiol, Sch Phys Educ, BR-13083970 Campinas, SP - Brazil

^[8] Univ Campinas UNICAMP, Dept Surg, Lab Invest Metab & Diabet LIMED, Gastroctr, BR-13083970 Campinas, SP - Brazil

^[9] Univ Campinas UNICAMP, Biomed Engn Ctr, Campinas, SP - Brazil

^[10] Univ Estadual Campinas, Dept Radiol, BR-13084970 Campinas, SP - Brazil

^[11] Univ Fed Uberlandia, Dept Pediat, Uberlandia, MG - Brazil

• Document type: Journal article
• Source: EBIOMEDICINE; v. 39, p. 436-447, JAN 2019.
• Web of Science Citations: 3

Abstract

Background: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue. Methods: The relations between IL10 and mitochondria structure/ function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice. Findings: IL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNF alpha monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression. Interpretation: IL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function. Fund: Sao Paulo Research Foundation grant 2013/07607-8. (c) 2018 The Authors. Published by Elsevier B.V. (AU)

• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC