Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C |
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Authors: | S P Y Wong M Huda P English A Bargiotta J P H Wilding A Johnson R Corrall J H Pinkney |
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Institution: | (1) Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK;(2) Diabetes and Endocrinology, Bristol Royal Infirmary, Bristol, UK;(3) Diabetes Centre, Southmead Hospital, Bristol, UK;(4) Department of Medicine, Royal Cornwall Hospital, Truro, TR13LJ, UK |
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Abstract: | Aims/hypothesis Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular
disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family
with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin
resistance and the metabolic syndrome.
Methods Plasma levels of adiponectin, leptin, resistin, IL-1β, IL-6 and TNF-α in 30 subjects (ten patients, 20 controls) were correlated
with indices of metabolic syndrome.
Results Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7±1.0 in FDLP cases vs 7.1±0.72 μg/ml
in controls, p=0.02), leptin (1.23±0.4 vs 9.0±1.3 ng/ml, p=0.002) and IL-6 (0.59±0.12 vs 1.04±0.17 pg/ml, p=0.047) and elevated TNF-α (34.8±8.1 vs 13.7±2.7 pg/ml, p=0.028), whereas IL-1β and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body
fat mass (controls, r=−0.44, p=0.036; FDLP, r=−0.67, p=0.025), insulin resistance (controls, r=−0.62, p=0.003; FDLP, r=−0.70, p=0.025) and other features of the metabolic syndrome. TNF-α concentrations were positively related to fat mass (controls,
r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1β and resistin did not demonstrate any correlations with the metabolic syndrome in either group.
Conclusions/interpretation Low adiponectin and leptin and high TNF-α were identified as the major plasma adipokine abnormalities in FPLD, consistent
with the hypothesis that low adiponectin and high TNF-α production may be mechanistically related, and perhaps responsible
for the development of insulin resistance and cardiovascular disease in FPLD. |
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Keywords: | Adipokines Adiponectin Diabetes Insulin resistance Lipodystrophy Obesity TNF-α |
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