HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. DurringtonRecent developments in lipodystrophyMelvin, Audreya,b; Stears, Annab; Savage, David B.a,b Author Information aMetabolic Research Laboratories, Wellcome Trust - MRC Institute of Metabolic Science, University of Cambridge bNational Severe Insulin Resistance Service, Wolfson Diabetes & Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust, United Kingdom Correspondence to Audrey Melvin, Metabolic Research Laboratories, Wellcome Trust - MRC Institute of Metabolic Science, University of Cambridge, United Kingdom. Tel: +00 44 1223 763200; e-mail: [email protected] Current Opinion in Lipidology: August 2019 - Volume 30 - Issue 4 - p 284-290 doi: 10.1097/MOL.0000000000000613 Buy Metrics Abstract Purpose of review Lipodystrophy syndromes have an estimated prevalence of 1.3–4.7 cases per million and as with other rare diseases conducting research can be challenging. The present review highlights recently published work that has provided insights into the field of non-HIV--associated lipodystrophy syndromes. Recent findings Lipodystrophies are a heterogenous group of disorders, as such research is often focused on specific subtypes of the condition. The identification of children carrying LMNA mutations has provided insights into the natural history of FPLD2, specifically that the adipose tissue phenotype predates the onset of puberty. Recent reports of PLIN1 heterozygous null variant carriers and the apparent absence of a lipodystrophy phenotype challenges our understanding of the molecular biology of perilipin 1 and its role in the pathogenesis of FPLD4. With a focus on therapeutics, studies delineating the differential responsiveness of PPARγ mutants to endogenous and synthetic ligands has illustrated the potential for pharmacogenetics to inform therapeutic decisions in lipodystrophy related to PPARG mutations, whereas robust human studies have provided insight into the food independent metabolic effects of leptin in lipodystrophy. Finally, rare syndromes of lipodystrophy continue to serve as an exemplar for the contribution of genetically determined adipose tissue expandability to metabolic disease in the general population. Summary Lipodystrophy research continues to illuminate our understanding of this rare disease and the possibility that lipodystrophy syndromes and the metabolic syndrome may have shared pathophysiology. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.