Stearoyl-coenzyme A desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-γ responsiveness

Aiwei Yao-Borengasser, Negah Rassouli, Vijayalakshmi Varma, Angela M. Bodles, Neda Rasouli, Resat Unal, Bounleut Phanavanh, Gouri Ranganathan, Robert E. McGehee, Philip A. Kern

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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; 10 wk 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 γ (PPARγ) as well as other PPARγ-responsive genes, including lipin-β, AGPAT2, RBP4, adiponectin receptors, CD68, and MCP1. When SCD1 expression was inhibited with a siRNA, lipin-β, AGPAT2,andthe adiponectin R2 receptor expression were decreased,andadipocyte MCP-1 was increased. Conclusions: SCD1 is closely linked to PPARγ expression in humans, and is increased by PPARγ agonists. The change in expression of some downstream PPARγ targets after SCD1 knockdown suggests that PPARγ up-regulation of SCD1 leads to increased lipogenesis and potentiation of adiponectin signaling.

Original languageEnglish
Pages (from-to)4431-4439
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number11
DOIs
StatePublished - Nov 2008

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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