title: PPARγ regulates expression of carbohydrate sulfotransferase 11 (CHST11/C4ST1), a regulator of LPL cell surface binding.
abstract: The transcription factor PPARγ is the key regulator of adipocyte differentiation, function and maintenance, and the cellular target of the insulin-sensitizing thiazolidinediones. Identification and functional characterization of genes regulated by PPARγ will therefore lead to a better understanding of adipocyte biology and may also contribute to the development of new anti-diabetic drugs. Here, we report carbohydrate sulfotransferase 11 (Chst11/C4st1) as a novel PPARγ target gene. Chst11 can sulphate chondroitin, a major glycosaminoglycan involved in development and disease. The Chst11 gene contains two functional intronic PPARγ binding sites, and is up-regulated at the mRNA and protein level during 3T3-L1 adipogenesis. Chst11 knockdown reduced intracellular lipid accumulation in mature adipocytes, which is due to a lowered activity of lipoprotein lipase, which may associate with the adipocyte cell surface through Chst11-mediated sulfation of chondroitin, rather than impaired adipogenesis. Besides directly inducing Lpl expression, PPARγ may therefore control lipid accumulation by elevating the levels of Chst11-mediated proteoglycan sulfation and thereby increasing the binding capacity for Lpl on the adipocyte cell surface.
authors.affiliation: Department of Metabolic Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Ismayil
authors.initials: I
authors.lastname: Tasdelen
authors.forename: Ruud
authors.initials: R
authors.lastname: Berger
authors.forename: Eric
authors.initials: E
authors.lastname: Kalkhoven
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000494:pharmacology*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D008071:Lipoprotein Lipase; D047495:PPAR gamma; D015238:Sulfotransferases; C557901:Chst11 protein, mouse; D000097811:Carbohydrate Sulfotransferases