Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 93, Issue 11, Pages 4431-4439Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2008-0782
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Funding
- Veterans Administration
- General Clinical Research Center [M01RR14288]
- National Institutes of Health [DK 39176, DK 71277, DK 71346]
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Context and Objective: Stearoyl-coenzyme A desaturase (SCD1) is the rate-limiting enzyme that converts palmitoyl-and stearoyl-coenzyme A to palmitoleoyl-and oleoyl-cownzyme A, respectively. SCD-deficient mice are protected from obesity, and the ob/ob mouse has high levels of SCD. This study was designed to better characterize SCD1 gene and protein expression in humans with varying insulin sensitivity. Design, Participants, and Setting: In a university hospital clinical research center setting, SCD1 gene expression was measured in sc adipose and vastus lateralis muscle of 86 nondiabetic subjects; 10wk of pioglitazone (45 mg daily) and metformin (1000 mg twice daily) treatment were assessed in 36 impaired glucose-tolerant subjects. Adipocytes were treated with pioglitazone, and SCD1 expression was attenuated with small interfering RNA (siRNA) to examine other adipocyte genes. Results: There was no significant relationship between adipose or muscle SCD1 mRNA and either body mass index or insulin sensitivity. After pioglitazone (but not metformin) treatment, there was a 2-fold increase in SCD1 mRNA and protein in adipose tissue. Pioglitazone also increased SCD1 in vitro. There were significant positive correlations between SCD1 and peroxisomal proliferator-activated receptor gamma(PPAR gamma) as well as other PPAR gamma-responsive genes, including lipin-beta, AGPAT2, RBP4, adiponectin receptors, CD68, and MCP1. When SCD1 expression was inhibited with a siRNA, lipin-beta, AGPAT2, and the adiponectin R2 receptor expression were decreased, and adipocyte MCP-1 was increased. Conclusions: SCD1 is closely linked to PPAR gamma expression in humans, and is increased by PPAR gamma agonists. The change in expression of some downstream PPAR gamma targets after SCD1 knockdown suggests that PPAR gamma up-regulation of SCD1 leads to increased lipogenesis and potentiation of adiponectin signaling. (J Clin Endocrinol Metab 93: 4431-4439, 2008)
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