Format

Send to

Choose Destination
J Endocrinol. 2015 Jun;225(3):147-58. doi: 10.1530/JOE-15-0117. Epub 2015 Apr 13.

11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.

Author information

1
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.
2
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.
3
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.

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.

KEYWORDS:

11β-hydroxysteroid dehydrogenase type 1; adipocyte hypertrophy; adiponectin; fatty acid oxidation; glycolysis; mitochondria

PMID:
25869616
DOI:
10.1530/JOE-15-0117
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center