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11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.
J Endocrinol. 2015 Jun; 225(3):147-58.JE

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+Show Affiliations

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.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.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.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.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 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 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.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 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 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 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 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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25869616

Citation

Koh, Eun Hee, et al. "11β-HSD1 Reduces Metabolic Efficacy and Adiponectin Synthesis in Hypertrophic Adipocytes." The Journal of Endocrinology, vol. 225, no. 3, 2015, pp. 147-58.
Koh EH, Kim AR, Kim H, et al. 11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes. J Endocrinol. 2015;225(3):147-58.
Koh, E. H., Kim, A. R., Kim, H., Kim, J. H., Park, H. S., Ko, M. S., Kim, M. O., Kim, H. J., Kim, B. J., Yoo, H. J., Kim, S. J., Oh, J. S., Woo, C. Y., Jang, J. E., Leem, J., Cho, M. H., & Lee, K. U. (2015). 11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes. The Journal of Endocrinology, 225(3), 147-58. https://doi.org/10.1530/JOE-15-0117
Koh EH, et al. 11β-HSD1 Reduces Metabolic Efficacy and Adiponectin Synthesis in Hypertrophic Adipocytes. J Endocrinol. 2015;225(3):147-58. PubMed PMID: 25869616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes. AU - Koh,Eun Hee, AU - Kim,Ah-Ram, AU - Kim,Hyunshik, AU - Kim,Jin Hee, AU - Park,Hye-Sun, AU - Ko,Myoung Seok, AU - Kim,Mi-Ok, AU - Kim,Hyuk-Joong, AU - Kim,Bum Joong, AU - Yoo,Hyun Ju, AU - Kim,Su Jung, AU - Oh,Jin Sun, AU - Woo,Chang-Yun, AU - Jang,Jung Eun, AU - Leem,Jaechan, AU - Cho,Myung Hwan, AU - Lee,Ki-Up, Y1 - 2015/04/13/ PY - 2015/04/07/accepted PY - 2015/4/15/entrez PY - 2015/4/15/pubmed PY - 2015/8/12/medline KW - 11β-hydroxysteroid dehydrogenase type 1 KW - adipocyte hypertrophy KW - adiponectin KW - fatty acid oxidation KW - glycolysis KW - mitochondria SP - 147 EP - 58 JF - The Journal of endocrinology JO - J Endocrinol VL - 225 IS - 3 N2 - 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. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/25869616/11β_HSD1_reduces_metabolic_efficacy_and_adiponectin_synthesis_in_hypertrophic_adipocytes_ L2 - https://joe.bioscientifica.com/doi/10.1530/JOE-15-0117 DB - PRIME DP - Unbound Medicine ER -