Fatty acid synthase inhibitor, C75, blocks resistin-induced increases in lipid accumulation by human macrophages

Increasing adiposity (overweight and obesity) is associated with insulin resistance and increased risk of type II diabetes mellitus and cardiovascular disease. Adipose tissue is a highly active endocrine tissue, producing bioactive proteins called adipokines, such as leptin, apelin, adiponectin and resistin, which may link obesity and atherogenesis. Resistin, originally discovered in a search for novel adipocyte-derived molecules linking obesity and insulin-resistant diabetes [1], belongs to a new gene family of small cysteine-rich secretory proteins called ‘resistin-like molecules’ or RELMs. In rodents, resistin derives largely from adipose tissue and mice deficient in resistin (Retn [-/-]) are protected from obesity-associated insulin resistance [2]. In humans, expression of RETN, which shows significant sequence and tissue divergence from its murine counterpart, lies under the control of the myeloid-specific nuclear transcription factor CCAAT/enhancer-binding protein epsilon and is upregulated during monocyte–macrophage differentiation [3].