Original Article
European Journal of Clinical Nutrition (2006) 60, 1406–1413. doi:10.1038/sj.ejcn.1602471; published online 21 June 2006
Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance
Guarantors: K Gertow and RM Fisher.
Contributors: MR, PS, PE, BV, UdF, AH, M-LH.
K Gertow1,4, M Rosell2, P Sjögren1, P Eriksson1, B Vessby3, U de Faire2, A Hamsten1, M-L Hellenius1,5 and R M Fisher1
- 1Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- 2Division of Cardiovascular Epidemiology, Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- 3Department of Public Health and Caring Sciences, University of Uppsala, Uppsala, Sweden
- 4Laboratory of Cellular Biology and Biochemistry of Atherothrombosis, Monzino Cardiology Centre, Milano, Italy
- 5Centre for Family Medicine, Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden
Correspondence: Dr RM Fisher, Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institutet, Karolinska University Hospital (M1:01), SE-171 76 Stockholm, Sweden. E-mail: rachel.fisher@ki.se
Received 17 June 2005; Revised 12 April 2006; Accepted 17 May 2006; Published online 21 June 2006.
Abstract
Objective:
Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance.
Subjects:
75 subjects with a range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old Swedish men.
Measurements:
Anthropometric and biochemical variables (e.g. waist-hip-ratio (WHR) and homeostasis model assessment (HOMA) index of insulin sensitivity), FA composition of the subcutaneous (s.c.) gluteal adipose tissue, serum nonesterified FA (NEFA) and serum phospholipid compartments (by gas–liquid chromatography; n=294), and mRNA levels of FA handling proteins (adipocyte and keratinocyte lipid binding proteins, fatty acid transport protein (FATP) -1 and -4, CD36/fatty acid translocase, plasma membrane fatty acid binding protein, and acyl-CoA synthase-1 (ACS1)) in s.c. gluteal adipose tissue (by quantitative real-time polymerase chain reaction; n=75).
Results:
ACS1 expression was negatively correlated with measures of insulin resistance and central obesity (ACS1 versus HOMA: r=-0.28, P<0.05; ACS1 versus WHR: r=-0.23, P<0.05), with an opposite trend for FATP4. Further analysis of ACS1 expression levels revealed correlations with adipose tissue 16:0 (r=-0.27, P<0.05) and NEFA 16:1 (r=0.29, P<0.05), FA composition variables which in turn correlated with HOMA index (r=0.39, P<0.001 and r=-0.23, P<0.05, respectively, n=75). Moreover, NEFA 16:1 predicted ACS1 expression independently of HOMA, WHR and adipose tissue 16:0 in multiple regression analysis (standardized coefficient=0.27, P<0.05).
Conclusion:
Significant associations were found between measures of insulin sensitivity, adipose tissue FA handling protein expression, and specific FA composition variables. Although causal relationships could not be identified these findings suggest a role of FA handling proteins in relation to insulin sensitivity, via their involvement in FA trafficking and metabolism. In particular they indicate links between ACS1 activity, the distribution of 16:0 and 16:1, and insulin sensitivity, which may be of physiological relevance.
Keywords:
central obesity, insulin resistance, adipose tissue, fatty acid composition, fatty acid handling protein, expression
Abbreviations:
ACS1, acyl-CoA synthase-1; ALBP, adipocyte lipid binding protein; BMI, body mass index; CE, cholesteryl ester; CoA, coenzyme-A; FABP, fatty acid binding protein; FATP, fatty acid transport protein; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; KLBP, keratinocyte lipid binding protein; LDL, low-density lipoprotein; NEFA, nonesterified fatty acid; PL, phospholipid; SAD, sagittal abdominal diameter; SFA, saturated fatty acid; TG, triglyceride; VLDL, very low-density lipoprotein; WHR, waist-hip-ratio
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