Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance Export

@article{citeulike:2285975, abstract = {Abstract Aims/hypothesis\ \ Fatty acid desaturases introduce double bonds into growing fatty acid chains. The key desaturases in humans are Δ5-desaturase (D5D), Δ6-desaturase (D6D) and stearoyl-CoA desaturase (SCD). Animal and human data implicate hepatic desaturase activities in insulin resistance, obesity and dyslipidaemia. However, the role of desaturase activity in adipose tissue is uncertain. We therefore evaluated relationships between adipose mRNA expression, estimated desaturase activities (fatty acid ratios) in adipose tissue and insulin resistance. Methods\ \ Subcutaneous adipose tissue mRNA expression of D5D (also known as FADS1), D6D (also known as FADS2) and SCD was determined in 75 individuals representative of the study population of 294 healthy 63-year-old men. Desaturation indexes (product/substrate fatty acid ratios) were generated from adipose tissue fatty acid composition in all individuals. Insulin resistance was defined as the upper quartile of the updated homeostasis model assessment (HOMA-2) index. Results\ \ The relevant desaturation indexes (16:1/16:0, 18:1/18:0, 20:4/20:3 and 18:3/18:2) reflected expression of SCD, but not of D5D or D6D in adipose tissue. Insulin-resistant individuals had a higher adipose tissue 18:1/18:0, but not 16:1/16:0 ratio than insulin-sensitive individuals. Individuals with a high adipose tissue 18:1/18:0 ratio were 4.4-fold (95\% CI 1.8–11.8) more likely to be insulin resistant [threefold (95\% CI 1.1–8.6) after adjustment for waist circumference and plasma triacylglycerol]. In a multiple regression model predicting HOMA-2, the independent effect of the 18:1/18:0 ratio was borderline (p = 0.086). Conclusions/interpretation\ \ Adipose tissue desaturation indexes of SCD reflect the expression of the gene encoding the enzyme in this tissue. Elevated SCD activity within adipose tissue is closely coupled to the development of insulin resistance.}, author = {Sj\"{o}gren, P. and Sierra-Johnson, J. and Gertow, K. and Rosell, M. and Vessby, B. and de Faire, U. and Hamsten, A. and Hellenius, M. L. and Fisher, R.}, citeulike-article-id = {2285975}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00125-007-0876-9}, day = {1}, doi = {10.1007/s00125-007-0876-9}, journal = {Diabetologia}, keywords = {adiposity, homa, insulinresistance, molecular, obesity, physiology}, month = {February}, number = {2}, pages = {328--335}, posted-at = {2008-01-24 20:58:12}, priority = {2}, title = {Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance}, url = {http://dx.doi.org/10.1007/s00125-007-0876-9}, volume = {51}, year = {2008} }

TY - JOUR ID - citeulike:2285975 L3 - citeulike-article-id:2285975 N2 - Abstract Aims/hypothesis  Fatty acid desaturases introduce double bonds into growing fatty acid chains. The key desaturases in humans are Δ5-desaturase (D5D), Δ6-desaturase (D6D) and stearoyl-CoA desaturase (SCD). Animal and human data implicate hepatic desaturase activities in insulin resistance, obesity and dyslipidaemia. However, the role of desaturase activity in adipose tissue is uncertain. We therefore evaluated relationships between adipose mRNA expression, estimated desaturase activities (fatty acid ratios) in adipose tissue and insulin resistance. Methods  Subcutaneous adipose tissue mRNA expression of D5D (also known as FADS1), D6D (also known as FADS2) and SCD was determined in 75 individuals representative of the study population of 294 healthy 63-year-old men. Desaturation indexes (product/substrate fatty acid ratios) were generated from adipose tissue fatty acid composition in all individuals. Insulin resistance was defined as the upper quartile of the updated homeostasis model assessment (HOMA-2) index. Results  The relevant desaturation indexes (16:1/16:0, 18:1/18:0, 20:4/20:3 and 18:3/18:2) reflected expression of SCD, but not of D5D or D6D in adipose tissue. Insulin-resistant individuals had a higher adipose tissue 18:1/18:0, but not 16:1/16:0 ratio than insulin-sensitive individuals. Individuals with a high adipose tissue 18:1/18:0 ratio were 4.4-fold (95% CI 1.8–11.8) more likely to be insulin resistant [threefold (95% CI 1.1–8.6) after adjustment for waist circumference and plasma triacylglycerol]. In a multiple regression model predicting HOMA-2, the independent effect of the 18:1/18:0 ratio was borderline (p = 0.086). Conclusions/interpretation  Adipose tissue desaturation indexes of SCD reflect the expression of the gene encoding the enzyme in this tissue. Elevated SCD activity within adipose tissue is closely coupled to the development of insulin resistance. IS - 2 JF - Diabetologia EP - 335 TI - Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance VL - 51 SP - 328 KW - adiposity KW - homa KW - insulinresistance KW - molecular KW - obesity KW - physiology AU - Sjögren, P AU - Sierra-Johnson, J AU - Gertow, K AU - Rosell, M AU - Vessby, B AU - de Faire, U AU - Hamsten, A AU - Hellenius, ML AU - Fisher, R PY - 2008/02/01/ UR - http://dx.doi.org/10.1007/s00125-007-0876-9 ER -