Shall We Blame Too Much Food Or Too Little Leptins?

Among the most maligned individuals throughout history are the grossly obese. They are variously compared with similarly shaped animals and shunned by a society, which idolizes the perfectly shaped body and face. Yet we have long suspected that excessive intake of food may often play only a secondary role in creating their sorry state. Now researchers are beginning to unravel the mysteries behind why so many overweight individuals claim "I can starve myself for weeks, but I just keep gaining weight." And so we may soon discover that diet fads tend to fail in the long run because something is inherently wrong, perhaps in the brain itself.

Is it possible that certain substances might be genetically absent in some forms of obesity? In an article published two years ago in the journal Endocrinology, Ewart- Towland and colleagues studied the "Effect of the genetic background on the reproduction of leptin-deficient mice." It was becoming clear that the adipocyte hormone leptin plays a significant role in regulating energy balance. Studies done many years earlier spoke of an "obese gene" and it became well known that "mice with mutations in leptin or its receptors are hyperphagic (eat too much) and severely obese." These mice have numerous other problems as well such as diabetes, increased levels of cortisol in the blood, inability to produce offspring, poor tolerance of cold, and large fatty livers, which further contribute to their obesity.

Evidently leptin and leptin receptors may play an important role in creating at least certain kinds of obesity, but where does this occur in the body and is the effect limited to mice or are humans subject to similar effects? An article in Nature in 1998 by Friedman and Halaas spoke of the ability of leptin to regulate body weight in mammals while another article published even earlier, in 1994, in the same journal was entitled "Positional cloning of the mouse obese gene and its human homologue." It seems evident that studies of this sort are pointing to a definite role for leptin in humans as well as in mice. So when a group of distinguished researchers from The Rockefeller University led by Paul Cohen decide to publish their findings that "the brain is a direct target for the weight-reducing and neuroendocrine effects of leptin and that the liver abnormalities of db/db mice are secondary to defective signaling in the brain" the world of the diet creators should sit up and take notice. If this is really true for mice, it certainly behooves us to suspect that it may be true for humans as well.

Leptin deficient mice tend to recover considerably from their obesity and other changes when fed leptin. It's easy to extrapolate from this that the same should be true of humans. However, when dealing with humans it's never that simple. Certain conditions, and obesity definitely is one of them, have numerous causes. If you are to help a patient by replacing missing leptins, their receptors, or their obesity gene you must first prove that you have identified the correct reason for their obesity and then find a way to reverse the process appropriately.

The next time you accuse the overweight of overindulgence remember the leptin deficient obese mouse and tether your tongue with the thought that you may also possess some errant gene which may some future day express itself in a similarly embarrassing manner.

It's great to be an elephant, Just think of all that you can eat, And the bigger that you tend to get, The more your friends will think you're neat. Humans are really strange you know, Today it's thin, tomorrow plump, No sooner we decide the norm, Then back it goes into the dump. Could elephants have the right idea? Perhaps it's better to be large, In any event, I'd rather not argue, For the bigger the elephant the bigger the charge.