Cell metabolism research starts path towards exercise pill, better cancer treatments

We’re all aware that regular exercise is very important when it comes to maintaining levels of personal fitness as well as health, but most of us seem to have no time to pursue a workout regimen. According to the Centers for Disease Control and Prevention (CDC), nearly four out of five adult Americans do not achieve the minimum recommended amount for weekly exercise. This is unfortunate because the health benefits of regular exercise, including better blood circulation, increased metabolic efficiency, improved skeletal strength and increased lung capacity, are far better than most vitamin or health supplements can provide.

Although the American psyche may not always be interested in accomplishing the proper amount of exercise but it still craves the idea of being physically fit. And, as with most things, if there’s a quick shortcut to getting where we want to be, we’re going to try and take it. One merely has to look at our country’s long history of short-lived dieting fads, perhaps most recently manifested in the South Beach and Atkins diets, to see how we’ve tried to achieve personal fitness while getting around exercise. “Get fit quick” schemes are found all over our country’s popular culture, from Lucille Ball’s comedic attempt to shed pounds in I Love Lucy to the Saved by the Bell episode which takes a dramatic turn when DJ is confronted with her abuse of caffeine pills. Many individuals attempt all sorts of odd workout fads, including dog yoga or kinesiology tape, to try and shed pounds quickly.

The scientific world may be close to discovering chemical compounds useful for mimicking the biological processes stimulated by exercise, much to the delight of couch potatoes everywhere. In early October, researchers from Australia’s University of Sydney announced that they had discovered a blueprint for more than 1,000 molecular changes in muscle tissue caused by exercise. These molecular-level changes were identified with mass spectrometry techniques used on a group of men asked to engage in high-intensity exercise for short intervals. This is the most complete roadmap yet for understanding the physiological processes behind exercise and the belief is that this knowledge can be used to develop a therapeutic supplement that targets those same processes.

There are those who scoff at the idea of an exercise pill, seeing it as just one more excuse for lazy people to stay lazy. However, this type of treatment could be useful for patients suffering from cardiovascular disease or diabetes for whom exercise is very beneficial but for some reason, such as physical disability, is impossible to accomplish. Findings from the University of Sydney researchers were published in the research journal Cell Metabolism.

The incredible number of molecular changes occurring in muscle tissue because of physical activity and exercise points out the complexity of metabolism, the chemical processes occurring within every living organism in order to sustain life. The CDC lists eight major health benefits to regular exercise including losing weight by burning calories, strengthening the cardiovascular system, improving mood and can even increase a person’s longevity. There’s also evidence to suggest that regular exercise can increase levels of high-density lipoprotein cholesterol (HDL-C) in the blood, useful for promoting the digestion and disposal of cholesterol from the body. Finding compounds that can start those same molecular processes which are achieved by exercise becomes more possible as the secrets behind cellular metabolism are unlocked.

University-level research in America is also contributing to a better understanding of the biology behind weight loss. Scientists working at the Harvard Stem Cell Institute have found a method for using stem cells in the conversion of white fat cells, which stores energy as lipids, into brown fat cells, which burn stored energy. White fat cells also play a role in the development of diabetes and obesity whereas brown fat is associated with reduced resistance to insulin in diabetics. Researchers, in collaboration with Roche Pharmaceuticals (SWX:RO), studied a group of 1,000 compounds to find two which, when applied to white blood cells, encouraged metabolic activity causing those cells to mimic brown fat cells. The treatment did show some side effects in suppressing immune system activity.

A pair of signaling pathways for cellular processes targeted by physical exercise are the focus of cell metabolism research at the Salk Institute for Biological Studies in La Jolla, CA. A study authored by Ronald Evans of the Howard Hughes Medical Institute found that a nuclear receptor known as the peroxisome proliferator-activated receptor (PPAR) delta encourages weight loss when it interacts with activated forms of the metabolic regulator AMP-activated protein kinase (AMPK). Using mice, researchers were able to activate the AMPK with a synthetic form of adenosine monophosphate (AMP), a nucleotide which is produced during exercise. The treatment also had some effect in improving endurance in untrained, unconditioned mice, which were able to run more than 40 percent farther than similar mice who were not provided with the synthetic AMP.

The reprogramming of cellular metabolism has implications in human health that go well beyond staying in shape. Research conducted jointly at the University of Illinois at Chicago and Barcelona’s Universitat Pompeu Fabra has led to the recent discovery that a known tumor suppressor in humans is able to modify tumor behavior by promoting optimal cell metabolism. Scientists working on this study have found a genetically coded protein known as retinoblastoma protein (pRb) inhibits an enzyme which can make cancers more aggressive. Restoring the natural metabolism of pRb found in cancerous cells could slow the spread of cancer.

The role of genetics and cell metabolism in cancer activity is at the center of research being conducted at the University of Pennsylvania’s Abramson Cancer Center. Researchers are looking at a specific gene, known as Myc, which increases a person’s risk of cancer but also disrupts the metabolic pathways and internal rhythms of cancer cells. The altered rhythms of Myc-driven cancers may make chronotherapy, where treatment is applied at a specific time of day to optimize therapeutic benefits and minimize side effects, a better option to treat those cancers. The blocking of certain metabolic processes in cells for treating patients with lung cancer was the focus of collaborative research pursued by scientists at Montreal’s McGill University, Washington University in St. Louis, Russia’s ITMO University and the University of Bristol in England. This project has uncovered the fact that blocking an enzyme known as phosphoenolpyruvate carboxykinase (PEPCK) would prevent cancer cells from switching to glutamine as an energy source, which allows those cells to survive when glucose levels are low.

Yale University is working on the creation of an analytical platform that would improve the analysis of cellular metabolism down to the level of mitochondria, the organelle component of living cells responsible for the biological processes of respiration and energy production. The platform, known as Mass Isotopomeric Multi-Ordinate Spectral Analysis (MIMOSA), utilizes both nuclear magnetic resonance spectroscopy and mass spectroscopy into a single technique that allows scientists to observe multiple cellular metabolic processes at once; previous methods required looking at each process individually. The MIMOSA platform should lead to further discoveries in cell metabolism and its role in various diseases.