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- Title
Stearoyl-coenzyme A desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-gamma responsiveness.
- Authors
Yao-Borengasser, Aiwei; Rassouli, Negah; Varma, Vijayalakshmi; Bodles, Angela M; Rasouli, Neda; Unal, Resat; Phanavanh, Bounleut; Ranganathan, Gouri; McGehee, Robert E Jr; Kern, Philip A
- Abstract
<bold>Context and Objective: </bold>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.<bold>Design, Participants, and Setting: </bold>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.<bold>Results: </bold>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 (PPARgamma) as well as other PPARgamma-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.<bold>Conclusions: </bold>SCD1 is closely linked to PPARgamma expression in humans, and is increased by PPARgamma agonists. The change in expression of some downstream PPARgamma targets after SCD1 knockdown suggests that PPARgamma up-regulation of SCD1 leads to increased lipogenesis and potentiation of adiponectin signaling.
- Subjects
PREVENTION of obesity; ANIMAL experimentation; COMPARATIVE studies; FAT cells; GENES; GENETIC techniques; GLUCOSE tolerance tests; HYPOGLYCEMIC agents; RESEARCH methodology; MEDICAL cooperation; MICE; OBESITY; OXIDOREDUCTASES; POLYMERASE chain reaction; PROTEINS; RESEARCH; RESEARCH funding; RNA; EVALUATION research; METFORMIN; REVERSE transcriptase polymerase chain reaction; SKELETAL muscle; THIAZOLIDINEDIONES; PHARMACODYNAMICS; PHYSIOLOGY
- Publication
Journal of Clinical Endocrinology & Metabolism, 2008, Vol 93, Issue 11, p4431
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2008-0782