miRNA-22 deletion limits white adipose expansion and activates brown fat to attenuate high-fat diet-induced fat mass accumulation

Author(s):Show less -

Lima, Vanessa M. ^[1] ; Liu, Jianming ^[2] ; Brandao, Bruna B. ^[3] ; Lino, Caroline A. ^[1] ; Silva, Camila S. Balbino ^[1] ; Ribeiro, Marcio A. C. ^[1] ; Oliveira, Tiago E. ^[4] ; Real, Caroline C. ^[5] ; Faria, Daniele de Paula ^[5] ; Cederquist, Carly ^[3] ; Huang, Zhan-Peng ^[6] ; Hu, Xiaoyun ^[2] ; Barreto-Chaves, Maria Luiza ^[1] ; Ferreira, Julio C. B. ^{[1, 7]} ; Festuccia, William T. ^[4] ; Mori, Marcelo A. ^[8] ; Kahn, C. Ronald ^[3] ; Wang, Da-Zhi ^[2] ; Diniz, Gabriela P. ^[1]

Affiliation

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

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

^[3] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA 02115 - USA

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med FMUSP, Dept Radiol & Oncol, Sao Paulo - Brazil

^[6] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Translat Med, NHC Key Lab Assisted Circulat, Guangzhou - Peoples R China

^[7] Stanford Univ, Dept Chem & Syst Biol, Sch Med, Stanford, CA 94305 - USA

^[8] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas - Brazil

• Document type: Journal article
• Source: METABOLISM-CLINICAL AND EXPERIMENTAL; v. 117, APR 2021.
• Web of Science Citations: 0

Abstract

Background: Obesity, characterized by excessive expansion of white adipose tissue (WAT), is associated with numerous metabolic complications. Conversely, brown adipose tissue (BAT) and beige fat are thermogenic tissues that protect mice against obesity and related metabolic disorders. We recently reported that deletion of miR-22 enhances energy expenditure and attenuates WAT expansion in response to a high-fat diet (HFD). However, the molecular mechanisms involved in these effects mediated by miR-22 loss are unclear. Methods and Results: Here, we show that miR-22 expression is induced during white, beige, and brown adipocyte differentiation in vitro. Deletion of miR-22 reduced white adipocyte differentiation in vitro. Loss of miR-22 prevented HFD-induced expression of adipogenic/lipogenic markers and adipocyte hypertrophy in murine WAT. In addition, deletion of miR-22 protected mice against HFD-induced mitochondrial dysfunction in WAT and BAT. Loss of miR-22 induced WAT browning. Gain-and loss-of-function studies revealed that miR-22 did not affect brown adipogenesis in vitro. Interestingly, miR-22 KO mice fed a HFD displayed increased expression of genes involved in thermogenesis and adrenergic signaling in BAT when compared to WT mice fed the same diet. Conclusions: Collectively, our findings suggest that loss of miR-22 attenuates fat accumulation in response to a HFD by reducing white adipocyte differentiation and increasing BAT activity, reinforcing miR-22 as a potential therapeutic target for obesity-related disorders. (c) 2021 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 17/01558-6 - Role of microRNA-22 in the adipogenesis and in the browning process of adipose tissue in obesity induced by high-fat diet
• Grantee: Vanessa Morais Lima
• Support type: Scholarships in Brazil - Post-Doctorate
• 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 type: Regular Research Grants
• FAPESP's process: 18/10338-2 - Role of microRNA-22 in differentiation of brown adipocytes and in browning of white adipose tissue
• Grantee: Gabriela Placoná Diniz
• Support type: Regular Research Grants
• FAPESP's process: 17/26528-2 - Role of microRNA-22 in adipogenesis and browning process of adipose tissue in high-fat diet-induced obesity
• Grantee: Vanessa Morais Lima
• Support type: Scholarships abroad - Research Internship - Post-doctor