Chondroprotection of leptin deficiency demystified?

Abstract

Using the unique preclinical model of lipodystrophy—a rare heterogeneous disorder characterized by the absence of subcutaneous adipose tissue—paracrine signaling from fat, rather than body weight, has been identified as a mediator of spontaneous and injury-induced joint degeneration1. Lipodystrophy is a leptin-deficient state that can be considered a lipid-partitioning disorder associated with severe insulin resistance, fatty liver, and hyperlipidemia (www.endotext.org). Other leptin-deficient states associated with extreme obesity are also chondroprotective, including deficiency due to a leptin gene mutation, as observed in ob/ob mice2, functional deficiency due to a leptin receptor gene mutation or silencing, as observed in db/db mice2, and lentiviral vector-mediated leptin receptor targeting3.