In what has been dubbed “The Great Crawl of China”, in August 2010 commuters in Beijing accumulated along a 74.5-mile-long stretch of road for a preposterous 11 days straight. No mere rush-hour delay, the absurdity of this pile-up—one of the worst in recorded history—suggests that multiple factors were to blame.
Just as fewer cars and properly functioning traffic signals keep the expressways clear and communal road rage (mostly) in check, the same principles can be applied to keeping our metabolism running smoothly.
In a Cell Perspectives paper published in December, Deborah Muoio, PhD, a Duke University researcher investigating the impact of diet and exercise on metabolic health, explains how overeating can be detrimental to our health by contributing to cellular traffic jams—and ultimately to obesity and metabolic disease.
Serving as the engines that transform nutrients into an energy currency the body can use, mitochondria’s job is to burn carbon intermediates that come primarily from two different types of fuel: fatty acids and carbohydrates in the form of glucose.
In normal physiology, mitochondria switch between alternate fuel sources throughout the day. Fuel choice depends on physiological cues such as if you’ve just polished off that plate of leftover holiday cookies, or if you are unfalteringly upholding your New Year’s resolution by hitting the gym.
During a fasting state the body preferentially burns fatty acids, which serves two purposes. First, it saves glucose from being depleted to dangerous levels, defending the body against low blood sugar. Second, because the brain is picky and heavily reliant on glucose, the other organs selflessly burn fatty acids instead, in effort to keep the mind sharp. By contrast, after eating, mitochondria switch to burning glucose as a preemptive strike to stave off high blood sugar.
Mitochondria directing carbon traffic from fatty acids and glucose in this stop-and-go fashion is an example of how the body works to support steady blood sugar levels. Maintaining blood sugar levels in this way has evolved as a consequence of our ancestor’s hunter-gatherer lifestyle to cope with dramatic fluctuations in energy supply and demand during periods of feast or famine. But then came mammoth fast food portions, donuts the size of small children, and literal tubs of movie theater popcorn. And, in consequence, overeating.
The problem is this: while the cellular mechanisms regulating energy metabolism have not changed much over the past several centuries, our environment is vastly different. Chowing down on that Big Mac and supersize portion of fries is bound to make mitochondria go berserk. They don’t know what to do with all the extra energy that they are now being force-fed.
With overeating—especially foods that are high in both fat and carbs—fatty acids and glucose are simultaneously trying to navigate the metabolic pathways. Rather than cooperating with the mitochondrial signals, these molecules clog pathways and antagonize one another, essentially throwing curse words and insulting gestures out the proverbial window, much like drivers during the infamous Beijing gridlock of 2010.
“When people eat too much and too often, there is more carbon traffic on the metabolic highways,” Muoio says. “When there are more carbon molecules, they can collide and cause damage to the cells.”
Chronic congestion in mitochondria leads to a state of metabolic confusion. This is akin to a malfunctioning traffic light flashing yellow—hindering the flow of traffic and pushing cells into a state of metabolic gridlock.
Around 15 years ago, the lab of David Kelley, MD, then at the University of Pittsburgh, had a hunch that what really matters for metabolic health might be the cell’s ability to select the right fuel for the right physiological setting (i.e. fasting or feeding, exercise or not). They found that in individuals who where obese or had type II diabetes, their mitochondria had lost the capacity to make this decision. In other words, mitochondria were unable to efficiently direct traffic. This is known as metabolic inflexibility and it has been linked with numerous ailments such as obesity, heart disease, and disorders of the liver and ovaries.
“Previous to this, most of the dialogue was centered on glucose uptake, but our work was telling us that there was a range of metabolic responses that we needed to focus on. We started to look at diseased states in more holistic ways,” Kelley says.
Although Kelley’s work provided the foundation, he asserts that researchers like Muoio have built upon his work in very elegant—and beneficial—ways.
Studies by Muoio and colleagues have shown that there are things that you can do to help your over-taxed cells return to an unobstructed state. She recommends grazing—eating smaller, more frequent meals—to keep metabolism running smoothly. In addition, an active lifestyle can have impressive benefits that extend beyond weight management.
“Exercise can unclog roadways by increasing the demand for the excess fuel we consume. Through exercise, the carbon molecules are burned at a much higher rate, so they aren’t colliding with one another,” Muoio says. “The cells are then better poised to cope with a new load of incoming carbon fuels.”
Although following these guidelines won’t prevent 11-day traffic jams from occurring along Beijing highways or on your daily commute, they will help to improve traffic flow at the cellular level, providing extra incentive for upholding a New Year’s resolution to eat less and move more.