Leptin may be key to controlling obesity

Obesity is arguably our most significant health epidemic. Almost two thirds of Australians are overweight or obese, and its associated diseases are a major concern for researchers. Professor Michael Cowley is the Director of the Monash Obesity and Diabetes Institute (MODI), which focuses on developing new therapies for obesity and diabetes. Michael is particularly interested in why leptin resistance is high in obese people. He's also looking at some of our most dangerous obesity-related diseases.

Leptin is a protein hormone that our fat cells secrete to regulate our appetite, metabolism and body weight. Earlier research has established leptin resistance in obese people, and Michael is now expanding on this finding.

"We have a project trying to understand how obesity causes leptin resistance and inflammation in the brain," Michael says. "Our early work described how leptin acted and from that, we worked out that the system became resistant and stopped responding. We published a paper with Tony Tiganis [a professor in the Department of Biochemistry and Molecular Biology] recently. We established a new enzyme that disrupts leptin signalling. We've shown that if we block this enzyme, we can help restore body weight control."

"That work also described how other signals from the body, for example your stomach and intestines, tell the brain how much food is in your stomach and intestines. That map of the brain helped us develop a couple of therapeutics for the treatment of obesity. These were spun out into a company I started called Orexigen Therapeutics, and we've just finished phase three trials," he says.

Another of Michael's major projects looks at blood glucose regulation in a completely new way. It has also led to clinical trials of an exciting new therapeutic.

"I'm looking at the role of the melanocortin system in regulating blood glucose levels, either through changing outflow from the brain, changing neural tone from the brain, or changing the secretion of pituitary hormones. I'm the director of a company that has a diabetes therapy in phase two trials. It's a novel drug for increasing insulin sensitivity in type two diabetics. Type two diabetes is caused by becoming insensitive to insulin, so a drug that increases insulin sensitivity will treat it. Eventually type two diabetics need insulin replacement, and this drug is for before that. It's an oral drug."

Michael's obesity research also applies to two more very different diseases, highlighting its translational benefits.

"We have a project looking at how obesity causes heart disease and [we are] developing a new therapeutic to treat obesity-induced heart disease. We think we've discovered why obesity gives you heart disease and we've preliminarily shown that we can reverse obesity-induced heart disease risks without reducing weight," he says.

"We're also doing some work on what causes poly-cystic ovarian syndrome and how that disease is exacerbated by obesity. It's a dominant cause of infertility in young women."

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