PMID- 12488352 OWN - NLM STAT- MEDLINE DCOM- 20030117 LR - 20161124 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 144 IP - 1 DP - 2003 Jan TI - Dehydroepiandrosterone down-regulates the expression of peroxisome proliferator-activated receptor gamma in adipocytes. PG - 253-9 AB - Dehydroepiandrosterone (DHEA) is expected to have a weight-reducing effect. In this study, we evaluated the effect of DHEA on genetically obese Otsuka Long Evans Fatty rats (OLETF) compared with Long-Evans Tokushima rats (LETO) as control. Feeding with 0.4% DHEA-containing food for 2 wk reduced the weight of sc, epididymal, and perirenal adipose tissue in association with decreased plasma leptin levels in OLETF. Adipose tissue from OLETF showed increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) protein, which was prevented by DHEA treatment. Further, we examined the effect of DHEA on PPARgamma in primary cultured adipocytes and monolayer adipocytes differentiated from rat preadipocytes. PPARgamma protein level was decreased in a time- and concentration-dependent manner, and DHEA significantly reduced mRNA levels of PPARgamma, adipocyte lipid-binding protein, and sterol regulatory element-binding protein, but not CCAAT/enhancer binding protein alpha. DHEA-sulfate also reduced the PPARgamma protein, but dexamethasone, testosterone, or androstenedione did not alter its expression. In addition, treatment with DHEA for 5 d reduced the triglyceride content in monolayer adipocytes. These results suggest that DHEA down-regulates adiposity through the reduction of PPARgamma in adipocytes. FAU - Kajita, Kazuo AU - Kajita K AD - The Third Department of Internal Medicine, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan. FAU - Ishizuka, Tatsuo AU - Ishizuka T FAU - Mune, Tomoatsu AU - Mune T FAU - Miura, Atsushi AU - Miura A FAU - Ishizawa, Masayoshi AU - Ishizawa M FAU - Kanoh, Yoshinori AU - Kanoh Y FAU - Kawai, Yasunori AU - Kawai Y FAU - Natsume, Yoshiyuki AU - Natsume Y FAU - Yasuda, Keigo AU - Yasuda K LA - eng PT - Journal Article PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (Carrier Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Fabp7 protein, rat) RN - 0 (Fatty Acid-Binding Protein 7) RN - 0 (Fatty Acid-Binding Proteins) RN - 0 (Leptin) RN - 0 (Neoplasm Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Srebf1 protein, rat) RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - 0 (Transcription Factors) RN - 0 (Triglycerides) RN - 459AG36T1B (Dehydroepiandrosterone) RN - 57B09Q7FJR (Dehydroepiandrosterone Sulfate) SB - IM MH - Adipocytes/chemistry/*metabolism MH - Animals MH - CCAAT-Enhancer-Binding Protein-alpha/genetics MH - CCAAT-Enhancer-Binding Proteins/genetics MH - Carrier Proteins/genetics MH - Cell Differentiation MH - Cells, Cultured MH - DNA-Binding Proteins/genetics MH - Dehydroepiandrosterone/administration & dosage/*pharmacology MH - Dehydroepiandrosterone Sulfate/pharmacology MH - Diet MH - Dose-Response Relationship, Drug MH - Epididymis MH - Fatty Acid-Binding Protein 7 MH - Fatty Acid-Binding Proteins MH - Gene Expression Regulation/*drug effects MH - Kinetics MH - Leptin/blood MH - Male MH - *Neoplasm Proteins MH - *Nerve Tissue Proteins MH - Obesity/*metabolism MH - Polymerase Chain Reaction MH - RNA, Messenger/analysis MH - Rats MH - Rats, Inbred OLETF MH - Rats, Long-Evans MH - Receptors, Cytoplasmic and Nuclear/analysis/*genetics MH - Sterol Regulatory Element Binding Protein 1 MH - Transcription Factors/analysis/*genetics MH - Triglycerides/analysis EDAT- 2002/12/19 04:00 MHDA- 2003/01/18 04:00 CRDT- 2002/12/19 04:00 PHST- 2002/12/19 04:00 [pubmed] PHST- 2003/01/18 04:00 [medline] PHST- 2002/12/19 04:00 [entrez] AID - 10.1210/en.2002-220039 [doi] PST - ppublish SO - Endocrinology. 2003 Jan;144(1):253-9. doi: 10.1210/en.2002-220039.