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Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling
被引:82
作者:
Obrowsky, Sascha
[1
]
Chandak, Prakash G.
[1
]
Patankar, Jay V.
[1
]
Povoden, Silvia
[1
]
Schlager, Stefanie
[1
]
Kershaw, Erin E.
[3
]
Bogner-Strauss, Juliane G.
[4
]
Hoefler, Gerald
[2
]
Levak-Frank, Sanja
[1
]
Kratky, Dagmar
[1
]
机构:
[1] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria
[2] Med Univ Graz, Inst Pathol, Graz, Austria
[3] Univ Pittsburgh, Dept Med, Div Endocrinol, Pittsburgh, PA USA
[4] Graz Univ Technol, Inst Genom & Bioinformat, A-8010 Graz, Austria
基金:
奥地利科学基金会;
关键词:
triglyceride absorption;
cholesterol absorption;
enterocytes;
peroxisome proliferator-activated receptor alpha target genes;
HORMONE-SENSITIVE LIPASE;
MURINE SMALL-INTESTINE;
CHOLESTEROL ABSORPTION;
TRIACYLGLYCEROL LIPASE;
GENE-EXPRESSION;
FATTY-ACIDS;
IN-VIVO;
MICE;
ENTEROCYTES;
DEFICIENCY;
D O I:
10.1194/jlr.M031716
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:
Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [H-3] trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [H-3] oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPAR alpha target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPAR alpha-dependent processes also in the small intestine.-Obrowsky, S., P. G. Chandak, J. V. Patankar, S. Povoden, S. Schlager, E. E. Kershaw, J. G. Bogner-Strauss, G. Hoefler, S. Levak-Frank, and D. Kratky. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPAR alpha signaling. J. Lipid Res. 2013. 54: 425-435.
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页码:425 / 435
页数:11
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