Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia.
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 diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-alpha-/- mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an alpha-melanocyte-stimulating hormone analog, or CNTF(Ax15), a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-alpha-/- and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-alpha-/-, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTF(Ax15) treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTF(Ax15) 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.
Lee
Jennifer H
JH
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Stoneman 816, Boston, MA 02215, USA.
Bullen
John W
JW
Stoyneva
Violeta L
VL
Mantzoros
Christos S
CS
D000273:Adipose Tissue / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D020934:Ciliary Neurotrophic Factor / Q000031:analogs & derivatives / Q000494:pharmacology; D004032:Diet; D004167:Diphtheria Toxin / Q000235:genetics; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D015870:Gene Expression / Q000235:genetics; D006729:Hormones, Ectopic / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins; D015999:Multivariate Analysis; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D052243:Resistin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000071256:Uncoupling Protein 1; D000521:alpha-MSH / Q000819:agonists / Q000031:analogs & derivatives* / Q000494:pharmacology
D001786:Blood Glucose; D002352:Carrier Proteins; D020934:Ciliary Neurotrophic Factor; D004167:Diphtheria Toxin; D006729:Hormones, Ectopic; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D052243:Resistin; C499623:Retn protein, mouse; D014409:Tumor Necrosis Factor-alpha; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; C029795:diphtheria toxin fragment A; D000521:alpha-MSH