After spending twenty years in the rarified atmosphere of academic research and teaching medical school, followed by a long stint in the biotechnology industry, I decided to revisit a subject I used to teach: energy metabolism. Wow! This was a culture “shock and awe”.

Twenty years ago, we used to teach our budding doctors the simple fact that if there are more calories in the diet than are burned by physical activity. The excess energy is stored as fat. We understood in great detail, the metabolic pathways by which food is used to provide energy and the excess converted to fat. When it came to overeating, the message we gave our students, and they, in turn, gave to their patients, was the equivalent of “just say no”.

But this simple message has turned out to be overly simplistic; it was rooted in our understanding of why some people abuse drugs, especially the “recreational” variety. We really did not have a clue about what controls our appetite in the first place and what drives us to eat to excess. And here lies the reason for my excitement: The brain, which used to be a foreboding terra incognita, is now being explored like any other organ and is beginning to yield its secrets. And the fruits of this research are, well, mind-boggling.

We now know that the brain gets real-time information about the state of our hunger and satiety (sensation of fullness) on the one hand and the state of our “fatness” on the other through hormonal signals secreted by the gastrointestinal tract (grehlin, for instance) and by the fat cells (leptin). But how do these hormones function? And, where do these signals work in the brain? A lot has already been discovered, but the more we learn, the more we realize how little we know. An incredibly complex picture of appetite and of body weight control is emerging.

The hypothalamus is a region deep in the brain that was known for many years to play a role in food intake control. In the 1990s, sets of nerve cells (neurons) were discovered in the hypothalamus that signal to each other, thus forming neural circuits. It is now believed that these neural circuits may constitute the “regulator of energy balance”. If this is true, it is like finding the keys to the kingdom. We can now unleash a whole armamentarium of investigative techniques to shine a light on the inner workings of what used to be a “black box”.

Eventually, we should be able to identify in great detail the whole spectrum of hormones and peptides that affect these neurons. We should also be able to identify the receptors (proteins on the surface of cells that serve as docking molecules for these chemical signals). The interaction of hormones and peptides with their receptors typically leads to a cascade of biochemical events inside of the cell.

Using sophisticated biochemical technique, we can decipher the messages transmitted from the receptors to the inside of the nerve cell. We can also trace the message being transmitted from one cell to other cells throughout the whole circuit. And ultimately, we will be able to unravel how this symphony of signals controls our food intake behavior.

As we learn more and more about the pathways in the brain that control appetite and body weight, we will discover potential targets for the development of drugs that will modify those pathways. This could result in whole new approaches to the treatment of obesity and related conditions.

Echoes of a brave new world? Maybe. But like everything else in science-knowledge is neutral. It is what we do with it that will determine if it brings misery or incredible benefits to humankind.

In subsequent blogs, I hope to journey more deeply into the brave new world of the mind and how it affects our body weight and food-seeking behaviors.

Stay tuned.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.