title: Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.
abstract: 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 α (PPARα). 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 [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]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 PPARα 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 PPARα-dependent processes also in the small intestine.
authors.affiliation: Institute of Molecular Biology, Medical University of Graz, Graz, Austria.
authors.forename: Sascha
authors.initials: S
authors.lastname: Obrowsky
authors.forename: Prakash G
authors.initials: PG
authors.lastname: Chandak
authors.forename: Jay V
authors.initials: JV
authors.lastname: Patankar
authors.forename: Silvia
authors.initials: S
authors.lastname: Povoden
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schlager
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kershaw
authors.forename: Juliane G
authors.initials: JG
authors.lastname: Bogner-Strauss
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.forename: Sanja
authors.initials: S
authors.lastname: Levak-Frank
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kratky
mesh_terms: D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D055786:Gene Knockout Techniques; D006706:Homeostasis; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D008049:Lipase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009928:Organ Specificity; D047493:PPAR alpha / Q000378:metabolism*; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D002784:Cholesterol; D005230:Fatty Acids, Nonesterified; D008049:Lipase; D047493:PPAR alpha; D014280:Triglycerides; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases