Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy

Author(s)

Diniz, Gabriela Placona ^{[1, 2]} ; Huang, Zhan-Peng ^[2] ; Liu, Jianming ^[2] ; Chen, Jinghai ^[2] ; Ding, Jian ^[2] ; Fonseca, Renata Inzinna ^[1] ; Barreto-Chaves, Maria Luiza ^[1] ; Donato, Jr., Jose ^[3] ; Hui, Xiaoyun ^[2] ; Wang, Da-Zhi ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, SP - Brazil

^[2] Harvard Med Sch, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 - USA

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Clinical Science; v. 131, n. 24, p. 2885-2900, DEC 15 2017.
• Web of Science Citations: 9

Abstract

Obesity is associated with development of diverse diseases, including cardiovascular dis- eases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously, we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In the present study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high-fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alter HF diet induced cardiac hypertrophy or fibrosis in the heart. Our study therefore establishes miR-22 as an important regulator of dyslipidemia and suggests it may serve as a potential candidate in the treatment of dyslipidemia associated with obesity. (AU)

• FAPESP's process: 15/21859-5 - Role of microRNA-22 in the development of cardiac and metabolic alterations induced by high fat diet
• Grantee: Gabriela Placoná Diniz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50140-6 - Clams comprehensive Lab animal monitoring system
• Grantee: Jose Donato Junior
• Support Opportunities: Multi-user Equipment Program