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ARTD1 deletion causes increased hepatic lipid accumulation in mice fed a high-fat diet and impairs adipocyte function and differentiation
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
2833321
Author(s)
Erener, Süheda; Mirsaidi, Ali; Hesse, Mareike; Tiaden, André N; Ellingsgaard, Helga; Kostadinova, Radina; Donath, Marc Y; Richards, Peter J; Hottiger, Michael O
ARTD1 deletion causes increased hepatic lipid accumulation in mice fed a high-fat diet and impairs adipocyte function and differentiation
Journal
The FASEB Journal
Volume
26
Number
6
Pages / Article-Number
2631-8
Keywords
adipogenesis, ADP-ribosylation, liver, PARP-1
Abstract
ADP-ribosyltransferase Diphtheria toxin-like 1 [ARTD1; formerly called poly-ADP-ribose polymerase 1 (PARP1)] is a chromatin-associated enzyme involved in regulating metabolic homeostasis. The liver is at the core of glucose and lipid metabolism and is significantly affected by obesity and the metabolic syndrome. Here, we show that when fed a high-fat diet (HFD), mice lacking ARTD1 developed exacerbated hepatic steatosis. ARTD1(-/-) mice had a 19% higher liver weight than wild-type (WT) animals and exhibited a significantly increased serum concentration of cholesterol (38%) and impaired glucose tolerance. In addition, adipocyte function and size were significantly reduced in ARTD1(-/-) mice fed an HFD (7794 mum(2) for WT and 5579 mum(2) for ARTD1(-/-) mice). The significantly reduced adipogenic differentiation of adipose-derived stromal cells (ASCs) isolated from ARTD1(-/-) mice (28 vs. 11% Oil red O-positive cells in WT and ARTD1(-/-) ASCs, respectively) suggested that impaired adipogenesis as the underlying cause for this adipose tissue malfunction. This function of ARTD1 was specific for adipogenesis, since osteogenic differentiation was not affected by the ARTD1 deletion. In summary, we show that ARTD1(-/-) mice fed an HFD display impaired adipogenesis and show exacerbated hepatic steatosis, which can have important implications for nonalcoholic fatty liver disease.
