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# 1 of 7 April 30, 2008 06:05 (EDT)


Bradley Bale

I am relieved.
PDG2's main metabolite is 15-deoxyprostaglandin J2 which is a potent ligand of PPAR gamma. Ideal candidates for niacin therapy are insulin resistant patients. It should be beneficial to turn on PPAR gamma in these patients. Niacin's effect here may help explain the evidence for its apparent extra benefit in diabetics. Cordaptive would reduce this benefit by blocking PDG2. This would be a subtle signal compared to the lipid benefits and might take years of use before the adverse signal from this was strong enough for epidemiologists to recognize it. I believe the FDA made a good decision.

Cardiovascular Pathology Volume 17, Issue 4, July-August 2008, Pages 219-225
Original Article
Effect of niacin on adipocyte leptin in hypercholesterolemic rabbits

Jun Yang , a, , Shui-ping Zhaoa, , Jing Lia and Shao-zhuang Donga
aDepartment of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China
Abstract
Background
Leptin may play an important role in the development of atherosclerosis. Several transcription genes [including peroxisome proliferator-activated receptor ? (PPAR?) and CD36] involved in lipid and glucose metabolism and inflammatory processes may correlate to leptin expression. The aim of this study was to investigate the effect of niacin on serum leptin levels in hypercholesterolemic rabbits and the expression of leptin, PPAR?, and CD36 in adipocytes from hypercholesterolemic rabbits.
Methods
Eighteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (a) high-cholesterol group (n=6), which is maintained on high-cholesterol diet for 6 weeks, and (b) niacin group (n=6), which receives the same cholesterol diet plus niacin (200 mg/kg/day) for 6 weeks. The control group (n=6) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of niacin on leptin release was assayed in hypercholesterolemic rabbit adipocytes. Leptin levels in serum and adipocyte culture supernatant were measured via enzyme-linked immunosorbent assay. RT-PCR was used to evaluate leptin, PPAR?, and CD36 mRNA expression in adipose and adipocytes.
Results
Compared with the control group, rabbits fed with high-cholesterol diets showed higher levels of serum total cholesterol, low-density lipoprotein cholesterol, and leptin, all of which were significantly reduced by niacin treatment. After 6 weeks of treatment with niacin, the leptin level was significantly decreased by 21.8% (6.87±1.58 vs. 8.79±1.45, P

Prostaglandins &Other Lipid Mediators
Article in Press, Corrected Proof - Note to users
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doi:10.1016/j.prostaglandins.2011.01.002 | How to Cite or Link Using DOI
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Niacin promotes adipogenesis by reducing production of anti-adipogenic PGF2? through suppression of C/EBP?-activated COX-2 expression




References and further reading may be available for this article. To view references and further reading you must purchase this article.


Ko Fujimori, a, and Fumio Amanoa

a Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Received 19 November 2010; revised 22 December 2010; accepted 4 January 2011. Available online 12 January 2011.

Abstract
Niacin is converted to NAD and NADP in tissues, whose products are involved in a number of cellular processes; and it is associated with the regulation of adipogenesis. In this study, we identified the molecular mechanism by which niacin promotes the adipogenesis in mouse 3T3-L1 cells. When the cells were cultured with niacin, the expression of adipogenic peroxisome proliferator-activated receptor ?, CCAAT enhancer binding protein (C/EBP)?, and their target genes was enhanced concomitant with an increase in triglyceride storage. Moreover, niacin suppressed the expression of cyclooxygenase-2 and decreased the production of prostaglandin (PG) F2? in the early phase of adipogenesis, which PG suppresses the progression of adipogenesis via the PGF2? receptor. Furthermore, niacin decreased the C/EBP? level in the early phase of adipogenesis. These results indicate that niacin promoted adipogenesis by suppressing the production of the anti-adipogenic PGF2? through down-regulation of C/EBP?-activated cyclooxygenase-2 expression in adipocytes.

Research highlights
Niacin enhanced the expression of adipogenic PPAR?, C/EBP?, and their target genes in adipocytes. Niacin increased the accumulation of intracellular triglyceride storage. Niacin suppressed the production of anti-adipogenic PGF2? by down-regulation of C/EBP?-activated cyclooxygenase-2 expression in adipocytes.

Keywords: Niacin; C/EBP?; COX-2; PGF2?; Adipocytes

Abbreviations: COX, cyclooxygenase; PG, prostaglandin; AKR, aldo–keto reductase; PPAR ?, peroxisome proliferator-activated receptor ?; C/EBP, CCAAT enhancer binding protein; TBP, TATA-binding protein; aP2, fatty acid binding protein 4, adipocytes; EIA, enzyme immunoassay; ChIP, chromatin immunoprecipitation