title: Hormonal and nutritional regulation of lipogenic enzyme mRNA levels in rat primary white and brown adipocytes.
abstract: Hyroid hormone stimulates hepatic lipogenesis in the rat by increasing the expression of relevant genes, including acetyl-CoA carboxylase and fatty acid synthase. S14 mRNA, which encodes a protein thought to be involved in lipogenesis, responds in parallel. The effects of thyroid hormone on lipogenesis in white and brown adipose tissue are less clear, and may be complicated by indirect effects of the hormone. Rat white and brown preadipocytes were therefore isolated, grown to confluence, and used to test direct effects of thyroid hormone, insulin, and glucose. Lipogenesis was assessed by tritiated water incorporation, and acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and S14 mRNAs were measured by Northern analysis. Insulin (1 nM) increased lipogenesis about 9-fold in both white and brown adipocytes. Similar increases were seen in the levels of the three mRNAs. Thyroid hormone (1 microM) stimulated lipogenesis and acetyl-CoA carboxylase, fatty acid synthase, and S14 mRNA levels up to 2-fold in both types of adipocyte in the presence or absence of insulin. A high carbohydrate level (25 mM glucose) had no effect on lipogenesis compared to a low carbohydrate level (5 mM glucose) in white and brown adipocytes. There was no synergistic effect on lipogenesis by the combination of thyroid hormone and high carbohydrate level in both types of adipocytes. These experiments have shown that T3 has small, direct stimulatory effects on lipogenesis in adipocytes. These effects are seen at a pre-translational level, through the coordinate induction of ACC, FAS, and S14 mRNAs. Although lipogenic rates were usually higher in brown adipocytes than white adipocytes, very similar patterns of regulation were seen in the two cell types. These data support the idea that the divergent results seen concerning T3 regulation of the lipogenic pathway in both brown and white adipose tissue in vivo arise from secondary effects of the alteration of thyroid status.
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269-4017, USA.
authors.forename: Hedley Christopher
authors.initials: HC
authors.lastname: Freake
authors.forename: Yangha Kim
authors.initials: YK
authors.lastname: Moon
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D017667:Adipocytes / Q000201:enzymology*; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D006728:Hormones; D007328:Insulin; D008055:Lipids; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C051065:THRSP protein, human; C501478:Thrsp protein, rat; D014157:Transcription Factors; D014284:Triiodothyronine; D003907:Dexamethasone; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase