Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C.
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-1beta, IL-6 and TNF-alpha 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 mug/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-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta 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-alpha 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-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group.



Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.
Wong
S P Y
SP
Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.
Huda
M
M
English
P
P
Bargiota
A
A
Wilding
J P H
JP
Johnson
A
A
Corrall
R
R
Pinkney
J H
JH
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D003923:Diabetes Mellitus, Lipoatrophic / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007797:Laminin / Q000235:genetics* / Q000502:physiology; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D052243:Resistin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D052242:Adiponectin; D007375:Interleukin-1; D015850:Interleukin-6; D007797:Laminin; D020738:Leptin; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha; C084098:laminin A