HSL null mice display defective lipolysis due to diminished expression of lipases and lipid droplet-associated proteins, reduced quantities of WAT with increased amounts of BAT, increased numbers of macrophages in WAT, are resistant to high-fat diet induced obesity secondary to an apparent increase in thermogenesis and energy expenditure, and have multiple alterations in the expression of genes involved in adipose differentiation, including transcription factors, markers of adipocyte differentiation, and enzymes of fatty acid and triglyceride synthesis. The gene discussed is LIPE; the disease is obesity due to melanocortin 4 receptor deficiency.