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Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice.
Veerapaneni, Praneet; Goo, Brandee; Ahmadieh, Samah; Shi, Hong; Kim, David S; Ogbi, Mourad; Cave, Stephen; Chouhaita, Ronnie; Cyriac, Nicole; Fulton, David J; Verin, Alexander D; Chen, Weiqin; Lei, Yun; Lu, Xin-Yun; Kim, Ha Won; Weintraub, Neal L.
Afiliación
  • Veerapaneni P; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Goo B; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Ahmadieh S; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Shi H; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Kim DS; Department of Medicine, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Ogbi M; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Cave S; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Chouhaita R; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Cyriac N; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Fulton DJ; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Verin AD; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Chen W; Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Lei Y; Vascular Biology Center, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Lu XY; Department of Medicine, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Kim HW; Department of Physiology, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
  • Weintraub NL; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd, Augusta, GA 30912, USA.
Biomolecules ; 14(4)2024 Apr 18.
Article en En | MEDLINE | ID: mdl-38672510
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Adipocitos / Hígado Graso / Histona Desacetilasas Límite: Animals Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Adipocitos / Hígado Graso / Histona Desacetilasas Límite: Animals Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza