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

Diabetologia. 2004 Jun;47(6):1118-25. doi: 10.1007/s00125-004-1417-4. Epub 2004 May 28.


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 (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/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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / anatomy & histology
  • Adipose Tissue / physiology*
  • Adult
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Fatty Acid Transport Proteins
  • Fatty Acid-Binding Proteins
  • Fatty Acids / genetics
  • Fatty Acids / metabolism*
  • Female
  • Humans
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Male
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Patient Selection
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Statistics as Topic / methods
  • Subcutaneous Tissue / anatomy & histology
  • Subcutaneous Tissue / physiology
  • TATA-Box Binding Protein / genetics
  • TATA-Box Binding Protein / metabolism
  • Twins, Monozygotic / genetics
  • Twins, Monozygotic / metabolism
  • Up-Regulation / genetics


  • CD36 Antigens
  • Carrier Proteins
  • Fatty Acid Transport Proteins
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • RNA, Messenger
  • Slc27a4 protein, mouse
  • TATA-Box Binding Protein