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

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.

Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome

“…HIV lipodystrophy, familial partial lipodystrophy and obesity have been associated with high circulating levels of TNF-α [39,51,52]. In our sample, no significant differences in TNF-α levels were observed between controls and HIV-infected patients, in patients with or without FMR-L or regarding the four categories of fat composition.…”

“…These relationships suggest that the remaining SAT in HIV-infected patients with moderate to severe lipoatrophy is dysfunctional rather than simply reduced in size, as for example, patients suffering from anorexia nervosa, a condition characterized by low body weight and severe global fat depletion (although not isolated subcutaneous adipose tissue), adiponectin levels are higher [38-40]. Findings of abnormal function or loss of adipose tissue in partial lipodystrophy syndromes (due to lamin A/C or to PPAR-γ receptor mutations) and low adiponectinemia also support the hypothesis that low adiponectin concentrations in HIV-infected subjects with low levels of SAT are due to lipodystrophy per se [39,40] . Thus, lipodystrophies are characterized not only by a fat decreased but also by dysfunction or loss of adipocytes [30].…”

Diet, obesity and diabetes: a current update

“…An adequate amount of adipose tissue is also essential for metabolic homoeostasis [36,54]: although obesity is intimately linked to insulin resistance and Type 2 diabetes, these conditions also develop in people with lipodystrophies [54] and occur in rodent models of lipodystrophy [24,54,55]. These findings have confirmed adipose tissue and its secreted adipokines in the axis between the detection of nutrient status and the maintenance of energy balance [18,35,56].…”

Intra-individual Variation of Plasma Adipokine Levels and Utility of Single Measurement of These Biomarkers in Population-Based Studies

“…Levels of IL-1h, TNF-a, and PAI-1 were somewhat lower in our study than levels reported elsewhere (7,42), and the median leptin level (2.8 ng/mL) was also lower than the levels reported in the Health ABC cohort (5.5 ng/mL), the San Antonio Center for Biomarkers of Risk of Prostate cohort (7.6 ng/mL; refs. 7, 43), and in some clinical studies (24,37,43,44). Similarly, the median adiponectin level (4.2 Ag/mL) was 2-to 7-fold lower than levels observed previously (7,21,24,37,44,45).…”