Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance.
OBJECTIVE
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 (Delta) 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 (DeltaFATP4 versus DeltaBMI; r=0.50, p=0.04; DeltaFATP4 versus Deltabody 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
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.
Gertow
K
K
Atherosclerosis Research Unit. King Gustaf V Research Institute, Karolinska Institutet, Karolinska Hospital Building M1, 171 76 Stockholm, Sweden.
Pietiläinen
K H
KH
Yki-Järvinen
H
H
Kaprio
J
J
Rissanen
A
A
Eriksson
P
P
Hamsten
A
A
Fisher
R M
RM
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology*; D000328:Adult; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018579:Patient Selection; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013223:Statistics as Topic / Q000379:methods; D040521:Subcutaneous Tissue / Q000033:anatomy & histology / Q000502:physiology; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism; D014430:Twins, Monozygotic / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D018955:CD36 Antigens; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D012333:RNA, Messenger; C493572:Slc27a4 protein, mouse; D035181:TATA-Box Binding Protein