We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pioglitazone Increases Stearoyl-CoA Desaturase (SCD) Gene Expression and Protein Levels in Humans.
- Authors
Rassouli, Negah; Yao-Borengasser, Aiwei; Varma, Vijayalakshmi; Bodles, Angela M.; Phanavanh, Bounleut; Rasouli, Neda; Kern, Philip A
- Abstract
SCD is a rate-limiting enzyme that converts palmitoyl- (16:0) and stearoly-CoA (18:0) to palmitolenyl- (16:1) and olenyl-CoA (18:1), respectively. SCD is highly regulated and ultimately determines the ratio of monounsaturated to saturated fatty acids in cells, which affects membrane fluidity. In a SCD knockout mouse model, the absence of SCD protected the animals against obesity and insulin resistance, and the leptin deficient ob/ob mouse was shown to have high level of SCD that normalized after treatment with leptin, suggesting a role for SCD in energy homeostasis. In humans, the role of SCD in insulin resistance and obesity is not fully described. To elucidate this association, we measured mRNA levels of SCD in adipose tissue of 87 non-diabetic covering a wide range of BMI (19-55 Kg/m2) and insulin sensitivity (SI) (0.51-10.94 x 104.min-1/µ U/ml). SCD mRNA levels did not correlate with either BMI or SI. When matched for BMI, there was no difference in mRNA level between normal (NGT) or impaired glucose tolerant (IGT) subjects. We then assessed the effects of two insulin-sensitizing drugs, pioglitazone (PIO) and metformin, on SCD expression in adipose tissues and muscles from 36 IGT subjects. Tenweek treatment with PIO caused a 2-fold (p=0.01) increase in SCD mRNA levels in adipose tissue and a 10-fold increase in muscle (p=0.04). Following PIO, similar increases in SCD protein levels were found in adipose tissue using immunoblotting. SCD mRNA levels did not change after treatment with metformin in either tissue. To verify these findings in an in vitro system, we examined the effect of PIO on SCD expression in cultured human adipocytes, and found that PIO increased SCD mRNA levels by 2.8 fold. Thus, the absence of SCD in mice was associated with leanness and insulin sensitivity, although humans demonstrated no relationship between obesity and SCD, and the improvement of insulin sensitivity with PIO actually increased SCD. A PPAR response element has been identified in the promoter of the SCD gene, and our data suggest that PIO directly stimulates SCD gene expression. Clinical implications of the link between PPAR agonists and SCD need further investigation.
- Subjects
HYPOGLYCEMIC agents; ENZYMES; FATTY acids; FLUIDITY of biological membranes; INSULIN resistance; LEPTIN; MESSENGER RNA; ADIPOSE tissues
- Publication
Diabetes, 2007, Vol 56, pA356
- ISSN
0012-1797
- Publication type
Article