10 years of studying metabolism, nutrition, and human energy—what have we REALLY learned?

| Written by sgammon
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Every day we read or hear something about a food that is bad for us, a fruit that will help us lose weight, or a supplement that will extend our lives beyond their natural endpoint. Unquestionably, every year a significant amount of money, research, and time is spent exploring the cause and prevention of obesity, diabetes, heart disease, and the myriad of other metabolic conditions that affect our health and well-being. But what do scientists think are the truly important things we have learned about our metabolism, diet, and exercise over the last decade?  And how is this leading to the next-generation of medicines to treat metabolic disorders?

We asked some of our scientific leaders at the SBP Center for Metabolic Origins of Disease the ONE meaningful fact they have learned in their research in the past 10 years. And, we asked that they explain it to a non-scientist. So for all you photographers, realtors, lawyers, and accountants, here is what they want you to know.

Sheila Collins, Ph.D., Professor in the Integrative Metabolism Program I research the biochemical processes that regulate body weight, and have studied for many years how the hormone adrenaline stimulates the metabolism of fat cells to 'burn' energy. We are especially interested in so-called 'brown' fat cells that burn and waste energy, such that it causes a net loss of fat tissue. A couple of years ago we realized that hormones made in your heart that help to lower blood pressure can promote the same events in fat cells including increasing the amount and activity of these brown fat cells. I felt like for all these previous years there had been an elephant in the room that I only recently noticed was there! So now of course we work on both of these hormone stimulators! Our goal is to find a way to increase energy expenditure in fat in the fight against obesity and the devastating conditions that accompany it such as diabetes, cardiovascular disease, and hypertension.

Peter Crawford, M.D., Ph.D., Director of Cardiovascular Metabolism My research is focused on the relationship between the body’s fuels (carbohydrates, fats, and amino acids, and ketones), how they are metabolized, and how this leads to metabolic diseases. As humans, our bodies have the amazing ability to select among multiple biological engines to burn the nutrients that we eat. It turns out that which engine our body chooses, and how well that engine performs, can tell us a lot about what diseases we might be susceptible to, and what kinds of personalized treatment might be appropriate to consider for people with obesity, diabetes, heart disease, and cancer.

One key observation we have made is that the ketogenesis metabolic pathway—the pathway that releases ketones into the body when fat is broken down—influences fatty liver disease, an obesity linked disorder that causes both heart disease and cirrhosis. We used to think that ketogenesis was the equivalent of an exhaust pipe for burning fat, only important only when sugar intake or use was very low. Now we know ketogenesis can identify people at risk of disease and serve as a possible target for therapy when sugar intake is normal or even elevated.

Stephen Gardell, Ph.D., Senior Director of Scientific Resources (Lake Nona) Our lab works on a molecule called nicotinamide adenine dinucleotide, or NAD for short. NAD has always been known to play an important role in the production of cell energy by serving as a cofactor for enzyme reactions. In recent years, there has been a tsunami of new information implicating a role for NAD in a slew of other important metabolic processes, such as DNA repair, cell signaling, gene regulation, and programmed cell death for cells that are no longer needed. Knowing these new tricks of this ‘old school’ master molecule has spurred us to look for drugs to increase NAD levels with a goal to treat a number of diseases such as diabetes, obesity, muscle frailty, neurodegeneration, and aging.

Daniel Kelly, M.D., Director of the Center for Metabolic Origins of Disease My lab investigates how the body metabolizes fuels, with an emphasis on diabetes and heart failure. Heart failure is a major and growing worldwide health problem. Unfortunately, treatment for this problem is unsatisfactory and is largely directed at the very late stages when the heart is irreversibly damaged. Our work has led to the interesting finding that the heart starves for energy in the early stages of cardiac dysfunction that leads to heart failure. This finding has unveiled exciting new avenues for effective therapies aimed at the prevention or early stage treatment of heart failure.


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