Expression of fatty-acid-handling proteins in... : Diabetologia (original) (raw)

Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance

K. Gertow
K. H. Pietiläinen
H. Yki-Järvinen
J. Kaprio
A. Rissanen
P. Eriksson
A. Hamsten
R. M. Fisher

Diabetologia

(

)

1118

1125

June 2004

| DOI: 10.1007/s00125-004-1417-4

Abstract

Aims/hypothesis

Protein-mediated trans-membrane and intracellular fatty acid trafficking are becoming increasingly recognised as biochemically and physiologically important concepts. Obesity and insulin resistance are polygenic disorders, heavily influenced by environmental and life-style factors, and are virtually always associated with disturbed fatty acid metabolism in adipose and other tissues. The aim of this study was to investigate mRNA expression levels of fatty-acid-handling proteins in adipose tissue in relation to markers of genetic and acquired obesity and insulin resistance.

Methods

We quantified mRNA expression of subcutaneous adipose tissue fatty-acid-handling proteins (ALBP, KLBP, FATP1, FATP4, CD36, ACS1) in 17 monozygotic twin-pairs with a range of intra-pair differences (Δ) in BMI and detailed measures of obesity and insulin resistance, allowing influences of genetic and non-genetic factors to be distinguished.

Results

In acquired obesity FATP4 expression was up-regulated independently of genetic background (ΔFATP4 versus ΔBMI; _r_=0.50, _p_=0.04; ΔFATP4 versus Δbody fat; _r_=0.59, _p_=0.01). Similarly, CD36 and FATP1 expression correlated with acquired differences in HDL cholesterol and non-esterified fatty acid concentrations respectively. Moreover, FATP4 and CD36 expression levels correlated with measures of obesity and insulin resistance that are influenced by both genetic and non-genetic factors (FATP4 versus BMI: _r_=0.53, _p_=0.0001; FATP4 versus body fat: _r_=0.51, _p_=0.002; FATP4 versus homeostasis model assessment [HOMA]: _r_=0.49, _p_=0.001; CD36 versus BMI: _r_=0.50, _p_=0.02; CD36 versus body fat: _r_=0.63, _p_=0.001; CD36 versus HOMA: _r_=0.34, _p_=0.06).

Conclusions/interpretation

These findings indicate that expression of specific adipose tissue fatty-acid-handling proteins is related to obesity and insulin resistance, and that, in particular, FATP4 plays a role in acquired obesity. Our results suggest that facilitated fatty acid trafficking is a physiologically and pathologically relevant phenomenon in man.