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


METHODS
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 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.


CONCLUSIONS
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.
Yao-Borengasser
Aiwei
A
Research, 598/151, Central Arkansas Veterans Healthcare System, Department of Medicine, 4300 West 7th Street, Little Rock, Arkansas 72205, USA.
Rassouli
Negah
N
Varma
Vijayalakshmi
V
Bodles
Angela M
AM
Rasouli
Neda
N
Unal
Resat
R
Phanavanh
Bounleut
B
Ranganathan
Gouri
G
McGehee
Robert E
RE
Kern
Philip A
PA
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D009765:Obesity / Q000235:genetics / Q000517:prevention & control; D047495:PPAR gamma / Q000187:drug effects / Q000502:physiology*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency* / Q000235:genetics*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014162:Transfection; D055815:Young Adult
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D008687:Metformin; D013230:Stearoyl-CoA Desaturase; D000077205:Pioglitazone