Dawn of the New Leptin Era

A decade ago I recognized the extreme importance of leptin to human health. Leptin is the king of hormones which impacts everything else in your body. My first book on the subject in 2002, Mastering Leptin, was the first translation of highly complex science into readable English for the general public – specifically addressing how to eat to be in harmony with leptin. This subject continues to evolve at a breakneck pace and is a shining beacon of hope for true health improvement, maintaining a vibrant quality of health, and extending your lifespan. The newly understood role of leptin in your brain is both sobering and exciting. It is sobering because of the millions of people of every age with leptin-related health-deteriorating problems. It is exciting because knowledge and consistent action offers a solutions from disease and improved health.

Leptin is the hormone that is made primarily in your white adipose tissue, (i.e., stored fat). Leptin production in your fat increases when you eat. The hormone enters your blood and travels up to your brain and crosses your blood brain barrier to your subconscious command and control center the hypothalamus gland. When levels in your brain get high enough it gives you a full signal, and then it gives your metabolism a go signal. The proper operation of this leptin-related feeding circuit, gives every other hormone in your body permission to operate, including thyroid hormone.

Leptin levels in your brain drop low for two main reasons: starvation and over-eating. Starvation is a normal reason for leptin levels to drop low, over-eating is not. When there is not much food around, your metabolism must run slower or you will perish. Your brain senses leptin just as you look at the gas gauge in your car to see if you need to go to the gas station. During evolution, food was often not readily available for extended periods of time, thus your body automatically slows everything down until more food is available – a low-leptin survival strategy of the utmost importance.

Eating too much causes excessively high levels of leptin in your blood along with excess numbers of fat blobs called triglycerides. The excess triglycerides cling on to leptin receptors at your blood brain barrier, in turn clogging leptin entry into your brain. This forces people to over-eat to drive leptin into their brain to get a full signal – typically requiring 30% - 200% more calories than is normal just to get a full signal and a consequent metabolic go signal. This problem is called leptin resistance. Your brain actually has low leptin levels – a false state of misperceived starvation. Your brain sets your hormones for starvation and running slow – yet your body is being overwhelmed with excess calories. Fat piles up while you feel like you are hibernating.

A cell's receptor for a hormone, answers the hormone phone call. Within the hypothalamus gland feeding-control center, leptin phone calls bind to leptin receptors that turn off hunger and food cravings on certain types of nerve cells (NPY - neuropeptide Y and AgRP -agouti-related protein) while binding to leptin receptors on other types of nerve cells that stimulate metabolism while reducing food intake (POMC -proopiomelanocortin and CART - cocaine and amphetamine–related transcript). When leptin levels in the brain drop low, the craving signals turn on and when you eat enough they turn off.

When leptin binds to a receptor, you can get either a go or stop signal depending on what that type of nerve cell it binds to. Importantly, when receptors no longer function properly, then phone calls are not answered and normal metabolism does not occur – regardless of the levels of hormone (this is true of any hormone system). Thus, if leptin receptors in your hypothalamus are not there in proper numbers you are headed for weight gain due to an inability to correctly get a full signal and metabolic go signal. The protection and maintenance of the receptors is as important as the hormone levels. It takes two to tango. Hormones make phone calls and receptors answer them.

The new science centers on what happens when leptin phone calls are answered. Leptin signaling into a cell activates multiple gene signals, depending on the cell type so activated. Not only do these gene signals impact hunger and satiety, they set off a chain reaction of gene signaling all over your body that is in many ways different than traditional concepts of hormonal regulation. These gene signals stimulate the energizing sympathetic nerves, regulate growth, influence your response to stress, and regulate many aspects of the cellular life cycle everywhere in your body. This is an unbelievably complex scenario of gene cross-talk. It is all designed to efficiently maintain energy distribution in relation to food availability and consumption, which is why it is all linked together via leptin. For example, what if you were starving yet had to flee from a saber-tooth tiger? The new gene science is painting a picture that leptin signaling is monitoring energy flux within your body and managing your response. This is a far more sophisticated understanding of leptin than as a simple full signal hormone that is only monitoring your stored fat levels.

All of this highly complex genetic signaling evolved during tens of thousands of years when food scarcity was a primary threat to survival. It is not hard to understand that excess food consumption can confuse and bewilder these genetic settings – making it much easier to gain weight than to lose weight.

The new science is showing that leptin problems with gene signaling cause an inappropriate uncoupling of energy production in cells all over your body (meaning less calorie combustion and consequent ATP/energy production). Leptin receptors in areas of your brain outside the hypothalamus gland are helping to process all the signals coming from the vagus nerve which are generated within your gut – which also influence metabolism and the inflammatory state. These findings link leptin, your gut, your brain, and your overall ability to make energy into one complex regulatory scheme.

The new science shows that leptin is active all over your brain, through highly connected and complex nerve circuits. This elevates the importance of understanding and managing leptin from the issues of food cravings and body weight to the very core essence of the function of your brain. This means that preserving proper leptin function in your brain is getting as close to the essence of what you consider yourself to be as anything yet understood. We are now getting into that fuzzy area where we start trying to figure out the nature of the human soul and how it communicates with the physical self to form the essence of whatever it is you consider yourself to be.

Of extreme importance is that analysis of leptin-related gene arrays shows that more than 9% of the genes activated by leptin have to do with protein metabolism that facilitates synaptic plasticity in your brain – which is the absolute bottom line of aging in your brain. This has been demonstrated in relationship to memory as well as in relationship to reward (dopamine drive). Proper leptin function has a profound influence on the health of your brain and even acts to protect your nerves from excitotoxic damage. Proper leptin gene signaling influences the speed of your brain's signaling ability, which is vital for optimal cognitive function. Leptin is not functioning as a minor player or some type of grunt worker, but rather the CEO that is running the show. In other words, the proper function of leptin is a primary issue for human ability as well as the prevention of all neurologic diseases associated with aging. This is truly a new era of science.

If you would like to read science, a good review article on key points of this posting can be read by clicking here¹ and following the links.

On July 4th our nation celebrates its freedom. The exercise of free will is best done by intelligent humans operating towards the mutual benefit of all members of society. The exercise of free will towards regularly eating anything you are addicted to has little to do with true free will and everything to do with being a misguided stimulus-response animal, quickly headed in the direction of stupid. Unfortunately our national trend is rapidly heading in that direction – marking the decay of a great nation. Celebrations on a grand scale typically involve lots of food – which is a really good thing to enjoy every now and then. Have a great 4th of July weekend. And then get yourself and loved ones firmly on the path to greater human potential. Changing society always requires that we lead by example.