Unknown

Dataset Information

0

Molecular mechanisms of hepatic steatosis and insulin resistance in the AGPAT2-deficient mouse model of congenital generalized lipodystrophy.


ABSTRACT: Mutations in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) cause congenital generalized lipodystrophy. To understand the molecular mechanisms underlying the metabolic complications associated with AGPAT2 deficiency, Agpat2 null mice were generated. Agpat2(-/-) mice develop severe lipodystrophy affecting both white and brown adipose tissue, extreme insulin resistance, diabetes, and hepatic steatosis. The expression of lipogenic genes and rates of de novo fatty acid biosynthesis were increased approximately 4-fold in Agpat2(-/-) mouse livers. The mRNA and protein levels of monoacylglycerol acyltransferase isoform 1 were markedly increased in the livers of Agpat2(-/-) mice, suggesting that the alternative monoacylglycerol pathway for triglyceride biosynthesis is activated in the absence of AGPAT2. Feeding a fat-free diet reduced liver triglycerides by approximately 50% in Agpat2(-/-) mice. These observations suggest that both dietary fat and hepatic triglyceride biosynthesis via a monoacylglycerol pathway may contribute to hepatic steatosis in Agpat2(-/-) mice.

SUBMITTER: Cortes VA 

PROVIDER: S-EPMC2673980 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Molecular mechanisms of hepatic steatosis and insulin resistance in the AGPAT2-deficient mouse model of congenital generalized lipodystrophy.

Cortés Víctor A VA   Curtis David E DE   Sukumaran Suja S   Shao Xinli X   Parameswara Vinay V   Rashid Shirya S   Smith Amy R AR   Ren Jimin J   Esser Victoria V   Hammer Robert E RE   Agarwal Anil K AK   Horton Jay D JD   Garg Abhimanyu A  

Cell metabolism 20090201 2


Mutations in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) cause congenital generalized lipodystrophy. To understand the molecular mechanisms underlying the metabolic complications associated with AGPAT2 deficiency, Agpat2 null mice were generated. Agpat2(-/-) mice develop severe lipodystrophy affecting both white and brown adipose tissue, extreme insulin resistance, diabetes, and hepatic steatosis. The expression of lipogenic genes and rates of de novo fatty acid biosynthesis were inc  ...[more]

Similar Datasets

| S-EPMC8089820 | biostudies-literature
| S-EPMC3471069 | biostudies-literature
| S-EPMC5070584 | biostudies-other
| S-EPMC6886673 | biostudies-literature
| S-EPMC1794117 | biostudies-literature
| S-EPMC3909042 | biostudies-literature
2013-08-07 | E-GEOD-39825 | biostudies-arrayexpress
2013-08-07 | GSE39825 | GEO
| S-EPMC3886666 | biostudies-other
| S-EPMC8465110 | biostudies-literature