Tags

Type your tag names separated by a space and hit enter

Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes.
Am J Physiol Endocrinol Metab. 2007 Apr; 292(4):E1213-22.AJ

Abstract

A clinically employed antihyperlipidemic drug, bezafibrate, has been characterized as a PPAR(alpha, -gamma, and -delta) pan-agonist in vitro. Recent extended trials have highlighted its antidiabetic properties in humans. However, the underlying molecular mechanism is not fully elucidated. The present study was designed to explore potential regulatory mechanisms of intracellular glucocorticoid reactivating enzyme, 11beta-HSD1 and anti-diabetic hormone, adiponectin by bezafibrate in murine adipose tissue, and cultured adipocytes. Treatment of db/db mice with bezafibrate significantly ameliorated hyperglycemia and insulin resistance, accompanied by a marked reduction of triglyceride and nonesterified fatty acids. Despite equipotent in lipid-lowering effects, another fibrate, fenofibrate, did not show such beneficial effects on glycemic control. Treatment of bezafibrate caused a marked decrease in the mRNA level of 11beta-HSD1 preferentially in adipose tissue of db/db mice (-47%, P<0.05), concomitant with a significant increase in plasma adiponectin level (+37%, P<0.01). Notably, treatment of bezafibrate caused a marked decrease in the mRNA level (-34%, P<0.01) and enzyme activity (-32%, P<0.01) of 11beta-HSD1, whereas the treatment substantially augmented the expression (+71%, P<0.01) and secretion (+27%, P<0.01) of adiponectin in 3T3-L1 adipocytes. Knockdown of 11beta-HSD1 by siRNA confirmed that 11beta-HSD1 acts as a distinct oxoreductase in adipocytes and validated the enzyme activity assays in the present study. Effects of bezafibrate on regulation of 11beta-HSD1 and adiponectin in murine adipocytes were comparable with those in thiazolidinediones. This is the first demonstration that bezafibrate directly regulates 11beta-HSD1 and adiponectin in murine adipocytes, both of which may contribute to metabolically-beneficial effects by bezafibrate.

Authors+Show Affiliations

Pharmacology Research Laboratory R and D, Kissei Pharmaceutica, Nagano, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

17190905

Citation

Nakano, Shigeru, et al. "Bezafibrate Regulates the Expression and Enzyme Activity of 11beta-hydroxysteroid Dehydrogenase Type 1 in Murine Adipose Tissue and 3T3-L1 Adipocytes." American Journal of Physiology. Endocrinology and Metabolism, vol. 292, no. 4, 2007, pp. E1213-22.
Nakano S, Inada Y, Masuzaki H, et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 2007;292(4):E1213-22.
Nakano, S., Inada, Y., Masuzaki, H., Tanaka, T., Yasue, S., Ishii, T., Arai, N., Ebihara, K., Hosoda, K., Maruyama, K., Yamazaki, Y., Shibata, N., & Nakao, K. (2007). Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes. American Journal of Physiology. Endocrinology and Metabolism, 292(4), E1213-22.
Nakano S, et al. Bezafibrate Regulates the Expression and Enzyme Activity of 11beta-hydroxysteroid Dehydrogenase Type 1 in Murine Adipose Tissue and 3T3-L1 Adipocytes. Am J Physiol Endocrinol Metab. 2007;292(4):E1213-22. PubMed PMID: 17190905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes. AU - Nakano,Shigeru, AU - Inada,Yoichi, AU - Masuzaki,Hiroaki, AU - Tanaka,Tomohiro, AU - Yasue,Shintaro, AU - Ishii,Takako, AU - Arai,Naoki, AU - Ebihara,Ken, AU - Hosoda,Kiminori, AU - Maruyama,Kazuyasu, AU - Yamazaki,Yoshinobu, AU - Shibata,Nobuo, AU - Nakao,Kazuwa, Y1 - 2006/12/26/ PY - 2006/12/28/pubmed PY - 2007/5/22/medline PY - 2006/12/28/entrez SP - E1213 EP - 22 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 292 IS - 4 N2 - A clinically employed antihyperlipidemic drug, bezafibrate, has been characterized as a PPAR(alpha, -gamma, and -delta) pan-agonist in vitro. Recent extended trials have highlighted its antidiabetic properties in humans. However, the underlying molecular mechanism is not fully elucidated. The present study was designed to explore potential regulatory mechanisms of intracellular glucocorticoid reactivating enzyme, 11beta-HSD1 and anti-diabetic hormone, adiponectin by bezafibrate in murine adipose tissue, and cultured adipocytes. Treatment of db/db mice with bezafibrate significantly ameliorated hyperglycemia and insulin resistance, accompanied by a marked reduction of triglyceride and nonesterified fatty acids. Despite equipotent in lipid-lowering effects, another fibrate, fenofibrate, did not show such beneficial effects on glycemic control. Treatment of bezafibrate caused a marked decrease in the mRNA level of 11beta-HSD1 preferentially in adipose tissue of db/db mice (-47%, P<0.05), concomitant with a significant increase in plasma adiponectin level (+37%, P<0.01). Notably, treatment of bezafibrate caused a marked decrease in the mRNA level (-34%, P<0.01) and enzyme activity (-32%, P<0.01) of 11beta-HSD1, whereas the treatment substantially augmented the expression (+71%, P<0.01) and secretion (+27%, P<0.01) of adiponectin in 3T3-L1 adipocytes. Knockdown of 11beta-HSD1 by siRNA confirmed that 11beta-HSD1 acts as a distinct oxoreductase in adipocytes and validated the enzyme activity assays in the present study. Effects of bezafibrate on regulation of 11beta-HSD1 and adiponectin in murine adipocytes were comparable with those in thiazolidinediones. This is the first demonstration that bezafibrate directly regulates 11beta-HSD1 and adiponectin in murine adipocytes, both of which may contribute to metabolically-beneficial effects by bezafibrate. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17190905/Bezafibrate_regulates_the_expression_and_enzyme_activity_of_11beta_hydroxysteroid_dehydrogenase_type_1_in_murine_adipose_tissue_and_3T3_L1_adipocytes_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00340.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -