TCD researchers are coming to grips with leptin, a hormone that controlsweight gain. Berni Dwan reports
It is all to do with a signalling hormone called leptin and how the brain and the body communicate about weight. The big "it" is obesity, the fastest growing health problem in the developed world.
Researchers are trying to establish if those of us who suffer from obesity are just the unfortunate victims of bad signalling, or if we are just greedy, because unlike animals, we can override the behavioural instinct to stop eating when full. Leptin is a signalling hormone released by our adipose tissue into the blood stream. Adipose tissue is connective tissue that functions as the major storage site for fat.
Leptin's primary target site is the hypothalamus, the brain's appetite centre. There it binds to receptors, stimulating neural pathways that control appetite. When leptin is released from fat cells it crosses the blood-brain barrier, positioning itself to tell the brain that the body has had enough to eat. If the brain doesn't receive the leptin signal, our appetite increases and we put on weight.
The neuroscience behind the control of appetite is in its infancy, but for Richard Porter, the discovery of leptin in 1994 by Jeffery Friedman has opened a door to a fascinating neuronal network and the world of appetite control. Dr Richard Porter and his research team in Trinity College Dublin's department of biochemistry are focusing on the role leptin plays in increasing "catabolism", the breakdown of nutrients by enzymes.
"Animal studies have shown that leptin promotes catabolism, in particular the burning-off of fat stores, but how leptin does this is not yet known," says Porter. "We have a particular interest in the organelles of the cell called mitochondria, which are the energy transducing engines of the cell. They, like any engine, work with a certain efficiency, and natural factors in our body can make them work more or less efficiently."
We all have different rates of metabolism, and the inefficiencies of metabolism have implications for obesity. Dr Porter believes that tweaking the mitochondria can make you lose weight.
"We have previously shown that leptin effects energy transducing efficiency in mouse liver (mice with no leptin became obese) and are about to submit a manuscript to the International Journal of Obesity showing that leptin decreases energy transducing efficiency in mouse skeletal muscle," says Dr Porter.
However, although leptin is a central player in the control of appetite, most humans who are obese or overweight do not have a problem with their leptin production, he says. "The more fat you have, the more leptin you produce. Although there are some examples of a single gene mutation causing obesity - like the humans who cannot produce leptin - they are unusual and rare. Clearly, a predisposition to be obese lies downstream of leptin production."
Lifestyle cannot be ignored. "The problem of obesity in Western society today, as evidenced by the increase in prevalence of children and adults who are overweight or obese, is much broader and multifactorial," says Dr Porter. "In general terms, one could view it as a problem of our behaviour superimposed upon our genetic make-up."
We can store food very well, that is why we have adipose tissue. But some people and some ethnic groups are better at storing than others, and the better you are at storing it the more susceptible you are to obesity if your food intake increases and your life becomes more sedentary.
Obese people have increased risk of type II diabetes, heart disease, high blood pressure, arthritis and early mortality. "There is no wonder-drug available," says Dr Porter. "Obesity is highest in the developed world where there is a readily available, limitless supply of good quality, high protein content, sugar rich food. Keeping your ideal weight is still a matter of controlling diet and increasing exercise."