Hormone sensitive lipase catalyzes the hydrolysis of diacylglycerol, and of triacylglycerol to a lesser extent, in lipolysis in adipose and non-adipose tissues and is involved in the supply of cholesterol for steroid-hormone production in adrenals and testis. These mice carry a targeted mutation in which exons 2 through 7 have been deleted. Mice that are heterozygous for this targeted mutation are viable and fertile. Although homozygous females are fertile, homozygous males are infertile due to gonadal hypotrophy and oligospermia. No gene product (mRNA or protein) is detected by Northern blot analysis of white adipose tissue, or Western blot analysis of white adipose, cardiac muscle, skeletal muscle, testis, and liver tissues. Homozygotes exhibit decreased white fat cell mass but significant brown fat cell hypertrophy. While triglyceride levels are reduced in cardiac muscle and liver, and elevated in brown adipose tissue; diacylglycerols accumulate in brown fat, white fat, skeletal and cardiac muscle, and testes of homozygotes. After fasting conditions, homozygotes exhibit reduced plasma levels of triacylglycerol and non-esterified fatty acids. Hydrolysis of triglycerides and diacylglycerols is impaired, resulting in decreased free fatty acid and glycerol release from white adipose tissue. Homozygous are partially protected against certain forms of cancer cachexia. Although body weight of female knock out mice is similar to that seen in controls, gonadal white adipose tissue mass is significantly reduced, and decreases progressively with age. Cholesteryl ester hydrolase activity is substantially decreased in brown and white adipose, cardiac and skeletal muscle, liver, kidney, testis, and brain tissue of knock out mice.
