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Regulated adipose tissue-specific expression of human AGPAT2 in lipodystrophic Agpat2-null mice results in regeneration of adipose tissue.


ABSTRACT: Genetic loss of Agpat2 in humans and mice results in congenital generalized lipodystrophy with near-total loss of adipose tissue and predisposition to develop insulin resistance, diabetes mellitus, hepatic steatosis, and hypertriglyceridemia. The mechanism by which Agpat2 deficiency results in loss of adipose tissue remains unknown. We studied this by re-expressing human AGPAT2 (hAGPAT2) in Agpat2-null mice, regulated by doxycycline. In both sexes of Agpat2-null mice, adipose-tissue-specific re-expression of hAGPAT2 resulted in partial regeneration of both white and brown adipose tissue (but only 30%-50% compared with wild-type mice), which had molecular signatures of adipocytes, including leptin secretion. Furthermore, the stromal vascular fraction cells of regenerated adipose depots differentiated ex vivo only with doxycycline, suggesting the essential role of Agpat2 in adipocyte differentiation. Turning off expression of hAGPAT2 in vivo resulted in total loss of regenerated adipose tissue, clear evidence that Agpat2 is essential for adipocyte differentiation in vivo.

SUBMITTER: Agarwal AK 

PROVIDER: S-EPMC10518674 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Regulated adipose tissue-specific expression of human <i>AGPAT2</i> in lipodystrophic <i>Agpat2</i>-null mice results in regeneration of adipose tissue.

Agarwal Anil K AK   Tunison Katie K   Vale Goncalo G   McDonald Jeffrey G JG   Li Xilong X   Scherer Philipp E PE   Horton Jay D JD   Garg Abhimanyu A  

iScience 20230901 10


Genetic loss of <i>Agpat2</i> in humans and mice results in congenital generalized lipodystrophy with near-total loss of adipose tissue and predisposition to develop insulin resistance, diabetes mellitus, hepatic steatosis, and hypertriglyceridemia. The mechanism by which <i>Agpat2</i> deficiency results in loss of adipose tissue remains unknown. We studied this by re-expressing human <i>AGPAT2</i> (hAGPAT2) in <i>Agpat2</i>-null mice, regulated by doxycycline. In both sexes of <i>Agpat2</i>-nul  ...[more]

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