Learning about liver tissue

A group of Australian researchers are pursuing ground-breaking work on receptors in muscle tissue which play an unexpectedly important part in regulating cholesterol levels.

The research is deciphering the functional role of the protein LXR, or LiverX Receptor in skeletal muscle tissue. LXR has been previously demonstrated to regulate genes involved in fat and cholesterol metabolism in a number of tissues including intestine, fat, arterial wall and liver.

That makes LXR a potential target for novel drugs against cardiovascular disease, atherosclerosis, obesity and diabetes. The research team from Queensland's Institute for Molecular Bioscience led by principal investigator Dr George Muscat has received a $435,000 NHMRC grant to tease out LXRs secrets.

They will be using microarray-based expression profiling to examine the functional role of LXR in skeletal muscle, and investigate the genetic programs activated by LXR involved in the regulation of cholesterol homeostasis and lipogenesis.

"Previously we thought the liver was the primary organ for maintaining cholesterol at appropriate levels in the body, but we now know that LXR is expressed in muscle and regulates the expression of genes that control HDL cholesterol levels, said Muscat. "Activation of LXR in muscle tissue induces transport of excess cholesterol and lipids to acceptor proteins -- high density lipoproteins (HDLs) which transfer cholesterol to the liver for breakdown and excretion.

"Our work provides evidence which supports previous studies demonstrating a correlation between exercise, percentage lean body mass, levels of good cholesterol (HDL cholesterol) and the reduced incidence of cardiovascular disease.

"Skeletal muscle accounts for about 40 per cent of a person's body weight and burns fats and sugars for energy, consequently it plays a significant role in the blood lipid profile. LXR is expressed in skeletal muscle, and it obviously has a vital role for cholesterol regulation in the body.

Muscat says drugs that target LXR have shown therapeutic utility in the reduction of cholesterol absorption and accumulation in fat and the arterial wall, which is beneficial in cardiovascular disease.

The IMB team has spent more than a year on preliminary research and Muscat, whose speciality is in nuclear hormone receptors and skeletal muscle, also completed a stint with US startup X-Ceptor Therapeutics, a company trying to develop novel therapeutics to reduce cholesterol levels.