Lipodystrophy is a rare condition where people have little or no body fat, which messes up metabolism, causing insulin resistance, high triglycerides, and fat building up in the wrong places. It’s probably more common than we think, so doctors should look for it and check for heart, metabolic, and other health problems. Studying this extreme lack of fat can also teach us about regular obesity.

Lipodystrophy constitutes a spectrum of diseases characterized by a generalized or partial absence of adipose tissue. Underscoring the role of healthy fat in maintenance of metabolic homeostasis, fat deficiency in lipodystrophy typically leads to profound metabolic disturbances including insulin resistance, hypertriglyceridemia, and ectopic fat accumulation. While rare, recent genetic studies indicate that lipodystrophy is more prevalent than has been previously thought, suggesting considerable underdiagnosis in clinical practice. In this article, we provide an overview of the etiology and management of generalized and partial lipodystrophy disorders. We bring together the latest scientific evidence and clinical guidelines and expose key gaps in knowledge. Through improved recognition of the lipodystrophy disorders, patients (and their affected family members) can be appropriately screened for cardiometabolic, noncardiometabolic, and syndromic abnormalities and undergo treatment with targeted interventions. Notably, insights gained through the study of this rare and extreme phenotype can inform our knowledge of more common disorders of adipose tissue overload, including generalized obesity.