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Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.
Arterioscler Thromb Vasc Biol. 2007 Mar; 27(3):635-41.AT

Abstract

OBJECTIVE

Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells.

METHODS AND RESULTS

Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi.

CONCLUSIONS

Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Authors+Show Affiliations

Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, B5, Yamada-oka, Suita, Osaka 565-0871, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17194889

Citation

Hiuge, Aki, et al. "Effects of Peroxisome Proliferator-activated Receptor Ligands, Bezafibrate and Fenofibrate, On Adiponectin Level." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 3, 2007, pp. 635-41.
Hiuge A, Tenenbaum A, Maeda N, et al. Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol. 2007;27(3):635-41.
Hiuge, A., Tenenbaum, A., Maeda, N., Benderly, M., Kumada, M., Fisman, E. Z., Tanne, D., Matas, Z., Hibuse, T., Fujita, K., Nishizawa, H., Adler, Y., Motro, M., Kihara, S., Shimomura, I., Behar, S., & Funahashi, T. (2007). Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(3), 635-41.
Hiuge A, et al. Effects of Peroxisome Proliferator-activated Receptor Ligands, Bezafibrate and Fenofibrate, On Adiponectin Level. Arterioscler Thromb Vasc Biol. 2007;27(3):635-41. PubMed PMID: 17194889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. AU - Hiuge,Aki, AU - Tenenbaum,Alexander, AU - Maeda,Norikazu, AU - Benderly,Michal, AU - Kumada,Masahiro, AU - Fisman,Enrique Z, AU - Tanne,David, AU - Matas,Zipora, AU - Hibuse,Toshiyuki, AU - Fujita,Koichi, AU - Nishizawa,Hitoshi, AU - Adler,Yehuda, AU - Motro,Michael, AU - Kihara,Shinji, AU - Shimomura,Iichiro, AU - Behar,Solomon, AU - Funahashi,Tohru, Y1 - 2006/12/28/ PY - 2006/12/30/pubmed PY - 2007/3/8/medline PY - 2006/12/30/entrez SP - 635 EP - 41 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 27 IS - 3 N2 - OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/17194889/Effects_of_peroxisome_proliferator_activated_receptor_ligands_bezafibrate_and_fenofibrate_on_adiponectin_level_ L2 - https://www.ahajournals.org/doi/10.1161/01.ATV.0000256469.06782.d5?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -