Familial partial lipodystrophy type 2 (FPLD2) is characterized by insulin resistance, adipose atrophy of the extremities and central obesity. Due to the resemblance with Cushing's syndrome, we hypothesized a putative role of glucocorticoid in the pathogenesis of metabolic abnormalities in FPLD2. Objective:To evaluate the phenotypic heterogeneity and glucocorticoid sensitivity in FPLD2 patients exhibiting the p.R482W or p.R644C LMNA mutations. Design, patients and measurements:Prospective study with FPLD2 patients (n = 24) and controls (n = 24), who underwent anthropometric, body composition, metabolic profile and adipokines/cytokine plasma measurements. Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5 and 1.0 mg of dexamethasone (DEX) given at 23:00 hours. Glucocorticoid receptor (GR) and 11βHSD isoforms expression were assessed by qPCR.Results: Familial partial lipodystrophy type 2 individuals presented increased waist and neck circumferences, decreased hip circumference, peripheral skinfold thickness and fat mass. Patients presented increased HOMA-IR, triglycerides, TNF-α, IL-1β, IL-6 and IL-10, and decreased adiponectin and leptin plasma levels. FPLD2 patients showed decreased ability to suppress the HPA axis compared with controls after 0.5 mg DEX. The phenotype was more pronounced in patients harbouring the p.R482W LMNA mutation. GRβ overexpression in PBMC was observed in female patients compared with female controls.Conclusions: Familial partial lipodystrophy type 2 patients exhibited anthropometric, clinical and biochemical phenotypic heterogeneity related to LMNA mutation sites and to gender. LMNA mutations affecting both lamin A and lamin C lead to more severe phenotype. FPLD2 patients also showed blunted HPA axis response to DEX, probably due to the association of increased levels of proinflammatory cytokines with GRβ overexpression leading to a more severe phenotype in female. K E Y W O R D Sfamilial partial lipodystrophy type 2, glucocorticoid sensitivity, insulin resistance, metabolic syndrome | 95 RESENDE Et al.
Meu eterno obrigada por sempre terem priorizado a nossa família e a educação, minhas maiores riquezas! Aos meus irmãos, Jorge e Marcelo, amigos inseparáveis e companheiros de profissão. Dividimos os melhores momentos da infância, os sabores das conquistas e também os amargos das decepções. Jorge, meu protetor e "companheiro de Turma", principal incentivador na minha formação acadêmica, exímio profissional, exemplo de determinação, competência e altruísmo. Marcelo, apesar do meu elo maternalista, é o meu gigante encorajador! Perspicácia diversificada, habilidoso e entusiasta, inspiração "savoir vivre". A vocês agradeço especialmente pelo acolhimento em Ribeirão Preto, amor, força e valiosos conselhos. À irmã que a vida me proporcionou, Graziela, amiga fiel e dedicada. Obrigada pela cumplicidade, ternura e cuidado. Você me traz ao equilíbrio e me fortalece! Agradeço especialmente a minha sogra, Wanda, que nunca poupou esforços e carinho para me ajudar. Obrigada pelo amor sincero e por sempre me acolher como sua filha. Aos cunhados, meu afeto por vocês vai além do propósito que nos uniu! Fabíola e Mariana, mais do que cunhadas, se tornaram verdadeiras amigas! Obrigada por me receberem com tanto esmero em suas casas e em suas vidas. Marco Aurélio, "cunhado-irmão", sempre disposto a ajudar e proteger. A vocês obrigada pelo companheirismo, receptividade, paciência e, epecialmente, pelo zelo com Ana Lis na minha ausência.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.