Leptin is an appetite suppressant which acts on specialized nerve cells in the brain and elsewhere to regulate food intake and body fat. At the time of its discovery in 1994 it was hailed as the decisive breakthrough that would lead to a cure for obesity. Unfortunately, as is so often the case in science, it turned out not to be the case.
Firstly it was assumed that observations made in mice would allow extrapolation to humans. Absence of leptin in mice resulted in weight gain, so (the theory went) low or absent leptin levels would turn out to be the underlying cause of obesity in humans. Once that was demonstrated, all that needed to be done was to develop a pill or even a nasal spray to deliver leptin and the obesity epidemic would be a distant memory.
Unfortunately, when researchers measured leptin in obese humans they found the levels to be high, rather than low suggesting that they are in some way insensitive to leptin rather than deficient. Since then a great deal of effort has gone into trying to understand the extremely complicated molecular mechanisms which are responsible for leptin resistance in humans. The work by Ozcan et al reported in Telegraph.co.uk begins to shed some light on these mechanisms, but it is frankly absurd at this stage to start talking about a leptin “revival”.
Firstly most researchers know (or should know) about the perils of making claims about the application to humans of research done in mice. Secondly, studies in humans which might exploit the work of Ozcan et al have not even started. As is so often the case, the journalists reporting such studies want to make claims that the researchers themselves are much more diffident about. This explains why in their paper, Ozcan and co-workers state that “Taken together, our results may provide the basis for a novel treatment of obesity”. The word “may” is important here and is – at least at this stage – not much more likely than “may not”.
The leptin story is far from over, but as a therapeutic possibility for the millions of obese people throughout the world, it remains a distant hope.
Dr David Ashton - January 2009
Ozcan L, Ergin AS, Lu Aet al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 2009; 9(1):35-51