期刊
DIABETES
卷 62, 期 1, 页码 124-136出版社
AMER DIABETES ASSOC
DOI: 10.2337/db11-1779
关键词
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资金
- College of Education and Human Ecology (EHE) Seed Grant
- Food Innovation Center Seed Grant
- Ohio State University (OSU) International Office Seed Grant
- Pilot Industry Partnership grant
- National Center for Research Resources [UL1RR025755]
- National Institutes of Health (NIH) [R01-ES-017290, R21-DK-088522]
- Alpha Omega Alpha Honor Medical Society
- NIB National Cancer Institute OSU Comprehensive Cancer Center Support Grant
- National Research Service Award grant [F32-DK-083903]
- College of Education and Human Ecology
- [R01-EY-013969]
- [P30-CA-16058-30]
- NATIONAL CANCER INSTITUTE [P30CA016058] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR023647, UL1RR025755] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R01EY013969] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [F32DK083903, R21DK088522] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES017290] Funding Source: NIH RePORTER
- Austrian Science Fund (FWF) [Z 136] Funding Source: researchfish
Mechanisms for sex- and depot-specific fat formation are unclear. We investigated the role of retinoic acid (RA) production by aldehyde dehydrogenase 1 (Aldh1a1, -a2, and -a3), the major RA-producing enzymes, on sex-specific fat depot formation. Female Aldh1a1(-/-) mice, but not males, were resistant to high-fat (HF) diet-induced visceral adipose formation, whereas subcutaneous fat was reduced similarly in both groups. Sexual dimorphism in visceral fat (VF) was attributable to elevated adipose triglyceride lipase (Atgl) protein expression localized in clusters of multilocular uncoupling protein 1 (Ucp1)-positive cells in female Aldh1a1(-/-) mice compared with males. Estrogen decreased Aldh1a3 expression, limiting conversion of retinaldehyde (Raid) to RA. Raid effectively induced Atgl levels via nongenomic mechanisms, demonstrating indirect regulation by estrogen. Experiments in transgenic mice expressing an RA receptor response element (RARE-lacZ) revealed HF diet-induced RARE activation in VF of females but not males. In humans, stromal cells isolated from VF of obese subjects also expressed higher levels of Aldh1 enzymes compared with lean subjects. Our data suggest that an HF diet mediates VF formation through a sex-specific autocrine Aldh1 switch, in which Raid-mediated lipolysis in Ucp1-positive visceral adipocytes is replaced by RA-mediated lipid accumulation. Our data suggest that Aldh1 is a potential target for sex-specific antiobesity therapy. Diabetes 62:124-136, 2013
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