Lipodystrophies: adipose tissue disorders with severe metabolic implications

Abstract

Lipodystrophy encompass a group of heterogeneous disorders consisting in marked reduction, absence, and/or the redistribution of adipose tissue. Lipodystrophy is frequently complicated with severe insulin resistance, diabetes, hyperlipidemia, and fatty liver. Anatomically, lipodystrophies can be partial or generalized. Etiologically, they can be congenital or acquired. Lipodystrophy diagnosis can be challenging, and it has been suggested that partial forms can be easily misdiagnosed as common central obesity with associated metabolic syndrome. Conventional insulin-sensitizing approaches usually fail to fully ameliorate insulin resistance in lipodystrophic patients. Leptin replacement is an approved therapy for the metabolic complications of congenital generalized lipodystrophy. Novel nutritional interventions are promising complementary approaches for treating lipodystrophy metabolic complications.

AGPAT2 deficiency impairs adipogenic differentiation in primary cultured preadipocytes in a non-autophagy or apoptosis dependent mechanism

“…Nowadays, 11 human AGPAT isoforms have been described, however, only mutations in AGPAT2 have been found in patients with congenital generalized lipodystrophy (CGL, Berardinelli-Seip syndrome) [2]. These patients develop extreme adipose tissue paucity, insulin resistance, hyperlipidemia, fatty liver and diabetes [3][4][5].…”

High incidence of BSCL2 intragenic recombinational mutation in Peruvian type 2 Berardinelli–Seip syndrome

“…These include congenital generalized lipodystrophy (CGL), a genetically heterogeneous group of disorders characterized by the nearly complete lack of functional adipocytes. Metabolic abnormalities such as hypertriglyceridemia and insulin resistance are also characteristic features of these disorders [Prieur et al, ; Cortes and Fernandez‐Galilea, ; Patni and Garg, ]. CGL is usually caused by pathogenic variants in either the AGPAT2 or the BSCL2 genes, which are responsible for a milder CGL1 and a more severe CGL2 (Berardinelli–Seip syndrome), respectively [Van Maldergem et al, ; Agarwal et al, ; Haghighi et al, ].…”

Skeletal energy homeostasis: a paradigm of endocrine discovery

“…Thus, despite its association with metabolic diseases, WAT performs many essential physiological functions. Indeed, in the absence, and/or the redistribution of adipose tissue (lipodystrophy), patients develop insulin resistance, hyperglycemia, hypertriglyceridemia, hepatic steatosis and polycystic ovary syndrome underscoring the importance of adipose formation for normal physiological function (Cortes & Fernandez-Galilea 2015).…”