Lipodystrophy: pathophysiology and advances in treatment

Abstract

Lipodystrophy is a medical condition characterized by complete or partial loss of adipose tissue. Not infrequently, lipodystrophy occurs in combination with pathological accumulation of adipose tissue at distinct anatomical sites. Patients with lipodystrophy suffer from numerous metabolic complications, indicating the importance of adipose tissue as an active endocrine organ. Not only does the total amount but also the appropriate distribution of fat deposits contribute to the metabolic state. Recent genetic and molecular research has improved our understanding of the mechanisms underlying lipodystrophy. Circulating levels of hormones secreted by adipose tissue, such as leptin and adiponectin, are greatly reduced in distinct subsets of patients with lipodystrophy, rationalizing the use of such hormones or agents that increase their circulating levels, such as peroxisome proliferator-activated receptor gamma (PPARγ) agonists, in a subset of patients with lipodystrophy. Other novel therapeutic approaches, including the use of growth hormone (GH) and GH-releasing factors, are also being studied as potential additions to the therapeutic armamentarium. Insights from recent research efforts and clinical trials could potentially revolutionize the treatment of this difficult-to-treat condition.

Adipokines and Aging

“…The metabolic consequences include fatty liver, dyslipidemia, insulin resistance and type 2 diabetes. The mechanisms underlying insulin resistance in lipodystrophy are not fully elucidated, but in a subgroup of the disease, adipokine dysregulation, including low levels of circulating leptin and adiponectin, is closely linked to metabolic dysregulation 20) . Moreover, recombinant leptin treatment improved glucose and triglyceride metabolism in patients with lipodystrophy, indicating that leptin signaling plays an essential role in metabolic abnormalities associated with lipodystrophy 21) .…”

Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints

“…Após a triagem, 12 estudos foram incluídos para revisão. A metanálise dos resultados de 226 pacientes mostrou que a TRL reduziu a glicemia de jejum Cases of lipodystrophy not associated with the use of highly active antiretroviral therapy (HAART) are rare conditions, and most determined by molecular defects in genes that regulate adipocyte differentiation, lipid metabolism, and lipid droplet morphology (1). As the adipose tissue is an important endocrine organ that synthesizes hormones with cytokine-like actions (known as adipokines) (2,3), its absence determines several metabolic defects, such as insulin resistance, diabetes, and hypertriglyceridemia, which can lead to the development of atherosclerosis, acute pancreatitis, and nonalcoholic fatty liver disease (NAFLD) (4).…”

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls

“…HIV-infected patients demonstrate significant changes in body composition (5) and may thus demonstrate abnormalities in GH secretion. Moreover, consideration has been given to increasing GH in HIV patients to improve metabolic abnormalities, and recombinant human GH (r-hGH) as well as a GHRH-releasing analog, recently been approved by the FDA in this regard, have been considered (6,7,20,21,22,23).…”