Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator–Activated Receptor-γ Action in Humans
- David B. Savage1,
- Ciaran P. Sewter1,
- Ellen S. Klenk2,
- David G. Segal2,
- Antonio Vidal-Puig1,
- Robert V. Considine2 and
- Stephen O’Rahilly1
- 1University Departments of Medicine and Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge, United Kingdom
- 2Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
Recent studies in murine models suggest that resistin (also called Fizz3 ), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator–activated receptor-γ (PPAR-γ) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase–polymerase chain reaction–based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-γ agonists markedly upregulated fatty acid–binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-γ (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-γ action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism.
Address correspondence and reprint requests to S. O’Rahilly, Department of Medicine, Box 157, Addenbrooke’s Hospital, Cambridge, CB2 2QR, U.K. E-mail:.
Received for publication 24 April 2001 and accepted in revised form 7 August 2001. Posted on the World Wide Web at http://www.diabetes.org/diabetes_rapids on 6 September 2001.
FABP4, fatty acid–binding protein-4; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PBMC, peripheral blood mononuclear cell; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PPAR-γ, peroxisome proliferator–activated receptor-γ; RT, reverse transcriptase; TNF-α, tumor necrosis factor-α; WAT, white adipose tissue.