Circulating irisin in relation to insulin resistance and the metabolic syndrome.
BACKGROUND
Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown.


OBJECTIVE
Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk.


METHODS
We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects.


RESULTS
Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = -0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66-33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72-19.60), high triglycerides (OR = 3.89, 95% CI = 1.16-13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18-9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes.


CONCLUSIONS
Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.
Harvard Medical School, JP9B52A, Boston, MA 02130. cmantzor@bidmc.harvard.edu.
Kyung Hee
KH
Park
Lesya
L
Zaichenko
Mary
M
Brinkoetter
Bindiya
B
Thakkar
Ayse
A
Sahin-Efe
Kyoung Eun
KE
Joung
Michael A
MA
Tsoukas
Eleni V
EV
Geladari
Joo Young
JY
Huh
Fadime
F
Dincer
Cynthia R
CR
Davis
Judith A
JA
Crowell
Christos S
CS
Mantzoros
D052242:Adiponectin / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001900:Boston / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology; D008875:Middle Aged; D008954:Models, Biological; D050177:Overweight / Q000150:complications; D012307:Risk Factors; D015854:Up-Regulation
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; C577593:FNDC5 protein, human; D005353:Fibronectins