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Friday, December 18, 2009

Leptin: Good for the Brain & Midsection


by JP Saleeby, MD

Leptin is a protein hormone seeing a lot of attention recently in the press.  The December 16th, 2009 issue of Journal of American Medical Association (JAMA) published an article relating Leptin levels and the incidence of Alzheimer's disease.  Leptin has in recent years been linked to obesity and fat metabolism.  The word leptin is derived from the Greek word leptos which means thin.  It is a 16 kilodalton protein derived from adipose tissue and associated with the Ob(Lep) gene on chromosome 7 in humans.  One of the main functions of Leptin is that it relays a message to the brain satiety centers when fat stores are low as seen during starvation.  Leptin levels respond quite rapidly going up when we over-feed and put on more adipose tissue and drop when we under-feed and loose adipose tissue.  The brain's response to this chemical messenger when we drop body fat and levels ofleptin are reduced is to shut down our satiety centers causing us to overeat.  This feed back system is what most researchers feel is responsible for theyoo-yoo dieting problems of "keeping the weight off" when we drop a lot of fat while dieting and exercising. 

In 2005 Dr. Rosenbaum and his team of researchers published research in the Journal of Clinical Investigation showing that injections of leptin in those fasting kept them from gaining back the unwanted fat after they had dieted.  Leptin's primary goal then is to defend and support body fat stores by increasing food seeking behavior when levels are too low.  The more fat cells you have the higher your leptin levels are.  It would be great to have a "leptin pill" that you could take to help thwart the rebound weight gain one often sees after dieting.  However, this is impractical for several reasons.  One, leptin in a pill form is useless as stomach acids will quickly destroy it before it gets absorbed.  Injecting leptin would be the alternative, but one would have to do it daily and for life to avoid weight gains and this would be cost prohibitive.  The way around this would be to "trick" the body into believing it was well fed by having "cheat days" or overfeeding days once or twice a week to produce enough leptin in the blood stream to prevent an over-eating frenzy.  According to the JAMA study with regards to serum leptin levels and Alzheimer's disease, it was shown that circulating leptin was associated with a reduced incidence of dementia and Alzheimer's disease in normal older adult test subjects.  Further research will be needed to determine how we can maintain health levels of leptin for our brains without having to become obese in the process.


Wolfgang, L., et. al, Association of Plasma Leptin Levels with Incident Alzheimer Disease and MRI measures of Brain Age., JAMA 2009;302(23):2565-2572

Rosenbaum, M. et. al, Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight., J. Clinical Investigations 2005;115, 3579-86



The herbal Garcinia cambogia was shown in a 2003 study by Dr. Hayamizu, et. al. studying the effects of G. cambogia extract on serum leptin and insulin in mice found that this extract has leptin like effects.  G. cambogia also known as Brindle Berry the rind of which is uses in India as a component in curry may be helpful as a leptin like modifier and weight loss supplement as one of its components is hydroxycitric acid (HCA) which in other studies has shown to reduce weight in subjects. Further trials will be necessary to prove effectiveness and safety since there are issues with HCA and hepatoxicity.  Although a study by Dr. Stohs, et. al as recently as the summer of 2009 showed no evidence of toxicity with HCA.


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