Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice

被引:0
|
作者
Veerapaneni, Praneet [1 ]
Goo, Brandee [1 ]
Ahmadieh, Samah [1 ]
Shi, Hong [1 ,2 ]
Kim, David S. [1 ]
Ogbi, Mourad [1 ]
Cave, Stephen [1 ]
Chouhaita, Ronnie [1 ]
Cyriac, Nicole [1 ]
Fulton, David J. [1 ,3 ]
Verin, Alexander D. [1 ,2 ]
Chen, Weiqin [4 ]
Lei, Yun [5 ]
Lu, Xin-Yun [5 ]
Kim, Ha Won [1 ,2 ]
Weintraub, Neal L. [1 ,2 ]
机构
[1] Augusta Univ, Med Coll Georgia, Vasc Biol Ctr, 1460 Laney Walker Blvd, Augusta, GA 30912 USA
[2] Augusta Univ, Med Coll Georgia, Dept Med, 1460 Laney Walker Blvd, Augusta, GA 30912 USA
[3] Augusta Univ, Med Coll Georgia, Dept Pharmacol & Toxicol, 1460 Laney Walker Blvd, Augusta, GA 30912 USA
[4] Augusta Univ, Med Coll Georgia, Dept Physiol, 1460 Laney Walker Blvd, Augusta, GA 30912 USA
[5] Augusta Univ, Med Coll Georgia, Dept Neurosci & Regenerat Med, 1460 Laney Walker Blvd, Augusta, GA 30912 USA
基金
美国国家卫生研究院;
关键词
HDAC9; overexpression; insulin resistance; adipose tissue; liver; HISTONE DEACETYLASE 9; METABOLIC DISEASE; TISSUE; PHYSIOLOGY; REGULATOR;
D O I
10.3390/biom14040494
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and hepatic steatosis, all of which were alleviated by global genetic deletion of Hdac9. Here, we developed a novel transgenic (TG) mouse model to test whether overexpression of Hdac9 is sufficient to induce adipocyte hypertrophy, insulin resistance, and hepatic steatosis in the absence of obesity. HDAC9 TG mice gained less body weight than wild-type (WT) mice when fed a standard laboratory diet for up to 40 weeks, which was attributed to reduced fat mass (primarily inguinal adipose tissue). There was no difference in insulin sensitivity or glucose tolerance in 18-week-old WT and HDAC9 TG mice; however, at 40 weeks of age, HDAC9 TG mice exhibited impaired insulin sensitivity and glucose intolerance. Tissue histology demonstrated adipocyte hypertrophy, along with reduced numbers of mature adipocytes and stromovascular cells, in the HDAC9 TG mouse adipose tissue. Moreover, increased lipids were detected in the livers of aging HDAC9 TG mice, as evaluated by oil red O staining. In conclusion, the experimental aging HDAC9 TG mice developed adipocyte hypertrophy, insulin resistance, and hepatic steatosis, independent of obesity. This novel mouse model may be useful in the investigation of the impact of Hdac9 overexpression associated with metabolic and aging-related diseases.
引用
收藏
页数:11
相关论文
共 50 条
  • [41] Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice
    Sinem Karaman
    Maija Hollmén
    Sun-Young Yoon
    H. Furkan Alkan
    Kari Alitalo
    Christian Wolfrum
    Michael Detmar
    Scientific Reports, 6
  • [42] Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance
    T. Ferre
    E. Riu
    S. Franckhauser
    J. Agudo
    F. Bosch
    Diabetologia, 2003, 46 : 1662 - 1668
  • [43] Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance
    Ferre, T
    Riu, E
    Franckhauser, S
    Agudo, J
    Bosch, F
    DIABETOLOGIA, 2003, 46 (12) : 1662 - 1668
  • [44] Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice
    Karaman, Sinem
    Hollmen, Maija
    Yoon, Sun-Young
    Alkan, H. Furkan
    Alitalo, Kari
    Wolfrum, Christian
    Detmar, Michael
    SCIENTIFIC REPORTS, 2016, 6
  • [45] Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance
    Ludwig, DS
    Tritos, NA
    Mastaitis, JW
    Kulkarni, R
    Kokkotou, E
    Elmquist, J
    Lowell, B
    Flier, JS
    Maratos-Flier, E
    JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03): : 379 - 386
  • [46] Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice
    Wu, Lan
    Parekh, Vrajesh V.
    Gabriel, Curtis L.
    Bracy, Deanna P.
    Marks-Shulman, Pamela A.
    Tamboli, Robyn A.
    Kim, Sungjune
    Mendez-Fernandez, Yanice V.
    Besra, Gurdyal S.
    Lomenick, Jefferson P.
    Williams, Brandon
    Wasserman, David H.
    Van Kaer, Luc
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (19) : E1143 - E1152
  • [47] Hepatic n-3 Polyunsaturated Fatty Acid Depletion Promotes Steatosis and Insulin Resistance in Mice: Genomic Analysis of Cellular Targets
    Pachikian, Barbara D.
    Essaghir, Ahmed
    Demoulin, Jean-Baptiste
    Neyrinck, Audrey M.
    Catry, Emilie
    De Backer, Fabienne C.
    Dejeans, Nicolas
    Dewulf, Evelyne M.
    Sohet, Florence M.
    Portois, Laurence
    Deldicque, Louise
    Molendi-Coste, Olivier
    Leclercq, Isabelle A.
    Francaux, Marc
    Carpentier, Yvon A.
    Foufelle, Fabienne
    Muccioli, Giulio G.
    Cani, Patrice D.
    Delzenne, Nathalie M.
    PLOS ONE, 2011, 6 (08):
  • [48] Hepatic Overexpression of SIRT3 in Mice Heterozygous for Mitochondrial Trifunctional Protein Rescues Hepatic Steatosis and Improves Insulin Sensitivity
    Nassir, Fatiha
    Arndt, Justin J.
    Ibdah, Jamal A.
    GASTROENTEROLOGY, 2015, 148 (04) : S973 - S973
  • [49] Inducible hepatic expression of CREBH mitigates diet-induced obesity, insulin resistance, and hepatic steatosis in mice
    Krumm, Christopher S.
    Xu, Xu
    Bare, Curtis J.
    Holman, Corey D.
    Kersten, Sander
    Dow, Lukas E.
    Lee, Ann-Hwee
    Cohen, David E.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 297 (01)
  • [50] Fisetin Alleviates Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice
    Choi, Myung-Sook
    Choi, Ji-Young
    Kwon, Eun-Young
    JOURNAL OF MEDICINAL FOOD, 2020, 23 (10) : 1019 - 1032