title: 11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.
abstract: Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin synthesis. We investigated whether 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression is increased in hypertrophic adipocytes and whether this is responsible for mitochondrial dysfunction and reduced adiponectin synthesis. Differentiated 3T3L1 adipocytes were cultured for up to 21 days. The effect of AZD6925, a selective 11β-HSD1 inhibitor, on metabolism was examined. db/db mice were administered 600 mg/kg AZD6925 daily for 4 weeks via gastric lavage. Mitochondrial DNA (mtDNA) content, mRNA expression levels of 11 β -H sd1 and mitochondrial biogenesis factors, adiponectin synthesis, fatty acid oxidation (FAO), oxygen consumption rate and glycolysis were measured. Adipocyte hypertrophy in 3T3L1 cells exposed to a long duration of culture was associated with increased 11 β -Hsd1 mRNA expression and reduced mtDNA content, mitochondrial biogenesis factor expression and adiponectin synthesis. These cells displayed reduced mitochondrial respiration and increased glycolysis. Treatment of these cells with AZD6925 increased adiponectin synthesis and mitochondrial respiration. Inhibition of FAO by etomoxir blocked the AZD6925-induced increase in adiponectin synthesis, indicating that 11β-HSD1-mediated reductions in FAO are responsible for the reduction in adiponectin synthesis. The expression level of 11 β -Hsd1 was higher in adipose tissues of db/db mice. Administration of AZD6925 to db/db mice increased the plasma adiponectin level and adipose tissue FAO. In conclusion, increased 11β-HSD1 expression contributes to reduced mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes.
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Eun Hee
authors: EH
authors: Koh
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Ah-Ram
authors: AR
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Hyunshik
authors: H
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Jin Hee
authors: JH
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Hye-Sun
authors: HS
authors: Park
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Myoung Seok
authors: MS
authors: Ko
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Mi-Ok
authors: MO
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Hyuk-Joong
authors: HJ
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Bum Joong
authors: BJ
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Hyun Ju
authors: HJ
authors: Yoo
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Su Jung
authors: SJ
authors: Kim
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Jin Sun
authors: JS
authors: Oh
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Chang-Yun
authors: CY
authors: Woo
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Jung Eun
authors: JE
authors: Jang
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Jaechan
authors: J
authors: Leem
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea.
authors: Myung Hwan
authors: MH
authors: Cho
authors: Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea Department of Internal Medicine University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Biomedical Research Center Asan Institute for Life Sciences, Seoul 138-736, Korea Department of Biological Sciences Konkuk University, Seoul 143-701, Korea kulee@amc.seoul.kr.
authors: Ki-Up
authors: KU
authors: Lee
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D041721:3T3-L1 Cells; D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006984:Hypertrophy; D050356:Lipid Metabolism / Q000187:drug effects; D008082:Lipotropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D063154:Mitochondrial Dynamics; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000517:prevention & control; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: C000600176:AZD6925; D052242:Adiponectin; D004791:Enzyme Inhibitors; D008082:Lipotropic Agents; D009536:Niacinamide; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000218:Adamantane
keywords: 11β-hydroxysteroid dehydrogenase type 1; adipocyte hypertrophy; adiponectin; fatty acid oxidation; glycolysis; mitochondria