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.
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页数:11
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