Congenital Lipodystrophies and Dyslipidemias

Abstract

Lipodystrophies are rare acquired and genetic disorders characterized by the selective loss of adipose tissue. One key metabolic feature of patients with congenital inherited lipodystrophy is hypertriglyceridemia. The precise mechanisms by which the lack of adipose tissue causes dyslipidemia remain largely unknown. In recent years, new insights have arisen from data obtained in vitro in adipocytes, yeast, drosophila, and very recently in several genetically modified mouse models of generalized lipodystrophy. A common metabolic pathway involving accelerated lipolysis and defective energy storage seems to contribute to the dyslipidemia associated with congenital generalized lipodystrophy syndromes, although the pathophysiological changes may vary with the nature of the mutation involved. Therapeutic management of dyslipidemia in patients with lipodystrophy is primarily based on specific approaches using recombinant leptin therapy. Preclinical studies suggest a potential efficacy of thiazolidinediones that remains to be assessed in dedicated clinical trials.

Congenital generalized lipodystrophies—new insights into metabolic dysfunction

“…14 Preclinical studies suggest a potential efficacy of thiazolidinediones that still needs to be assessed in clinical trials. 108,147 High doses of insulin are needed for most patients and some patients might experience dif ficulty injecting insulin because they lack subcutaneous fat in the abdomen or thighs. Patients with longstand ing diabetes mellitus might have diabetic nephropathy and endstage renal disease requiring haemodialysis and kidney transplantation.…”

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, ].…”

Hepatic Lipodystrophy in Galloway Calves

“…53 According to the cause and the anatomical distribution of adipose tissue, lipodystrophies are classified as genetic or acquired and generalized or partial, respectively. 37 Although the increased concentration of serum lipids in 2 calves and triglycerides in 1 calf as reported by Macleod and Allison 26 offers some evidence that this disease of Galloway calves is a bovine form of lipodystrophy, the proof is still lacking. Further investigations, including testing of the concentration of insulin in blood possibly enhanced by a glucose tolerance test, as well as blood concentration of lipids, namely triglycerides, have to be carried out indicating the described phenomenon being a lipodystrophy as defined in human medicine.…”

“…Further investigations, including testing of the concentration of insulin in blood possibly enhanced by a glucose tolerance test, as well as blood concentration of lipids, namely triglycerides, have to be carried out indicating the described phenomenon being a lipodystrophy as defined in human medicine. 37 …”