Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases after Pioglitazone Treatment and Is Associated with Peroxisomal Proliferator-Activated Receptor-γ Responsiveness

Autor: Philip A. Kern, Gouri Ranganathan, Aiwei Yao-Borengasser, Negah Rassouli, Neda Rasouli, Robert E. McGehee, Resat Unal, Vijayalakshmi Varma, Bounleut Phanavanh, Angela M. Bodles
Rok vydání: 2008
Předmět:
Male
Endocrinology
Diabetes and Metabolism
Receptor expression
Clinical Biochemistry
Mice
Obese
Adipose tissue
Peroxisome proliferator-activated receptor
Biochemistry
Mice
chemistry.chemical_compound
Endocrinology
Adipocyte
Adipocytes
RNA
Small Interfering
Mice
Knockout
chemistry.chemical_classification
Gene knockdown
Reverse Transcriptase Polymerase Chain Reaction
Middle Aged
Metformin
Female
Original Article
lipids (amino acids
peptides
and proteins)
Stearoyl-CoA Desaturase
medicine.drug
Adult
medicine.medical_specialty
Biology
Transfection
Gene Expression Regulation
Enzymologic
Young Adult
Internal medicine
medicine
Animals
Humans
Hypoglycemic Agents
Obesity
RNA
Messenger
Muscle
Skeletal
Aged
Pioglitazone
Adiponectin
Biochemistry (medical)
Glucose Tolerance Test
PPAR gamma
chemistry
Thiazolidinediones
Zdroj: The Journal of Clinical Endocrinology & Metabolism. 93:4431-4439
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jc.2008-0782
Popis: 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, and the adiponectin R2 receptor expression were decreased, and adipocyte 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.
Databáze: OpenAIRE
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