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1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: cmantzor{at}bidmc.harvard.edu.
Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance
and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose
tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia
in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum
resistin levels in lean C57BL/6J mice and various mouse models of obesity, including dietinduced
obese (DIO) C57BL/6J mice, high fat-fed TNF-
(-/-) mice, and brown adipose tissue
(BAT)-deficient UCP1-DTA mice. We also studied whether treatment with weight reducing and
insulin sensitizing compounds, i.e. MTII or CNTFAx15, alters resistin mRNA expression and/or
circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is
similar in obese DIO compared to lean C57BL/6J mice, as well as in TNF- (-/-) compared to
wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed
TNF- (-/-), and UCP1-DTA mice compared to lean controls. Moreover, although resistin
mRNA expression is up-regulated by MTII treatment for 24 hours and down-regulated by
CNTFAx15 treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or
CNTFAx15 treatment. In addition, serum resistin levels, but not resistin mRNA expression levels,
are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels
are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation
of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is
unlikely to play a major endocrine role in insulin resistance or glycemia in mice.
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