Vanessa M Lima1, Jianming Liu2, Bruna B Brandão3, Caroline A Lino1, Camila S Balbino Silva1, Márcio A C Ribeiro1, Tiago E Oliveira4, Caroline C Real5, Daniele de Paula Faria5, Carly Cederquist3, Zhan-Peng Huang6, Xiaoyun Hu2, Maria Luiza Barreto-Chaves1, Julio C B Ferreira7, William T Festuccia4, Marcelo A Mori8, C Ronald Kahn3, Da-Zhi Wang2, Gabriela P Diniz9. 1. Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. 2. Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 3. Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. 4. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. 5. Department of Radiology and Oncology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. 6. Center for Translational Medicine, The First Affiliated Hospital, NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China. 7. Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Department of Chemical and Systems Biology, Stanford University School of Medicine, California, USA. 8. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil. 9. Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: gpdiniz@usp.br.
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.
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.
Authors: Matteo Oliverio; Elena Schmidt; Jan Mauer; Catherina Baitzel; Nils Hansmeier; Sajjad Khani; Sandra Konieczka; Marta Pradas-Juni; Susanne Brodesser; Trieu-My Van; Deniz Bartsch; Hella S Brönneke; Markus Heine; Hans Hilpert; Emilio Tarcitano; George A Garinis; Peter Frommolt; Joerg Heeren; Marcelo A Mori; Jens C Brüning; Jan-Wilhelm Kornfeld Journal: Nat Cell Biol Date: 2016-02-22 Impact factor: 28.824
Authors: Tábatha de Oliveira Silva; Caroline A Lino; Vanessa C Buzatto; Paula Fontes Asprino; Yao Wei Lu; Vanessa M Lima; Renata I B Fonseca; Leonardo Jensen; Gilson M Murata; Sidney V Filho; Márcio A C Ribeiro; Jose Jr Donato; Julio C B Ferreira; Alice C Rodrigues; Maria Cláudia Irigoyen; Maria Luiza M Barreto-Chaves; Zhan-Peng Huang; Pedro A Favoretto Galante; Da-Zhi Wang; Gabriela P Diniz Journal: Cell Physiol Biochem Date: 2020-12-01
Authors: Krzysztof Koźniewski; Michał Wąsowski; Marta Izabela Jonas; Wojciech Lisik; Maurycy Jonas; Artur Binda; Paweł Jaworski; Wiesław Tarnowski; Bartłomiej Noszczyk; Monika Puzianowska-Kuźnicka; Alina Kuryłowicz Journal: Int J Mol Sci Date: 2022-05-26 Impact factor: 6.208