Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C

Springer Science and Business Media LLC - 2005
S. P. Y. Wong1, M. Huda1, P. English1, A. Bargiotta2, J. P. H. Wilding1, A. Johnson3, R. Corrall2, J. H. Pinkney1,4
1Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK
2Diabetes and Endocrinology, Bristol Royal Infirmary, Bristol, UK
3Diabetes Centre, Southmead Hospital, Bristol, UK
4Department of Medicine, Royal Cornwall Hospital, Truro, UK

Tóm tắt

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. 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. 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. 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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