Evaluation of epicardial adipose tissue in familial partial lipodystrophy

Abstract

BackgroundDunnigan type Familial Partial Lipodystrophy (FPLD) is characterized by loss of subcutaneous fat from the limbs and excessive accumulation on the visceral adipose tissue (VAT). Affected individuals have insulin resistance (IR), diabetes, dyslipidemia and early cardiovascular (CV) events, due to their imbalanced distribution of total body fat (TBF). Epicardial adipose tissue (EAT) is correlated with VAT. Hence, EAT could be a new index of cardiac and visceral adiposity with great potential as a marker of CV risk in FPLD.ObjectiveCompare EAT in FPLD patients versus healthy controls. Moreover, we aimed to verify if EFT is related to anthropometrical (ATPM) and Dual-Energy X-ray Absorptiometry (DEXA) measures, as well as laboratory blood findings. We postulated that FPLD patients have enlarged EAT.MethodsThis is an observational, cross-sectional study. Six patients with a confirmed mutation in the LMNA gene for FPLD were enrolled in the study. Six sex, age and BMI-matched healthy controls were also selected. EFT was measured by transthoracic echocardiography (ECHO). All participants had body fat distribution evaluated by ATPM and by DEXA measures. Fasting blood samples were obtained for biochemical profiles and also for leptin measurements.ResultsMedian EFT was significantly higher in the FPLD group than in matched controls (6.0 ± 3.6 mm vs. 0.0 ± 2.04 mm; p = 0.0306). Additionally, FPLD patients had lower leptin values. There was no significant correlation between EAT and ATPM and DEXA measurements, nor laboratory findings.ConclusionsThis study demonstrates, for the first time, that EAT measured by ECHO is increased in FPLD patients, compared to healthy controls. However, it failed to prove a significant relation neither between EAT and DEXA, ATPM or laboratory variables analyzed.

Evaluation of the hypothalamic–pituitary–adrenal axis in a case series of familial partial lipodystrophy

“…All patients in our series had an FMR > 1.2, and the cut-off point suggested in a previous study involving FPL type 2 carriers had a sensitivity of 88.9% and a specificity of 93.8% for clinical diagnosis [50]. The index also demonstrated prognostic relevance, indicating that the severity of FPL is determined by the degree of loss of subcutaneous adipose tissue [2–4, 8, 51].…”

Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice

“…To note, cardiac MRI in patients with congenital generalized lipodystrophy due to BSCL1 or BSCL2 pathogenic variants also show a concentric LV hypertrophy, independent of blood pressure, which could be due to increased myocardial triglyceride content [45]. In addition, epicardial fat has been shown to be increased in LMNA-associated partial lipodystrophy [46]. Therefore, whatever their underlying molecular cause, ectopic lipid storage and lipotoxicity-driven defects could contribute to cardiac hypertrophy in lipodystrophic syndromes.…”

Massive labial lipomatous hypertrophy in familial partial lipodystrophy seen on computed tomographic angiography

“…Through clinical findings and genetic testing, our patient was found to have FPLD type 2, which is due to an autosomal dominant heterozygous missense mutation in the LMNA gene, responsible for encoding nuclear lamin proteins A and C. A hyperinflammatory state caused by endoplasmic reticulum stress is also thought to play a role in the pathogenesis of type 2 FPLD, or Dunnigan type lipodystrophy [7]. Patients characteristically will develop diabetes and dyslipidemias, which predisposes them to early cardiovascular disease [8].…”