The Couch Potato Gene
Rogelio V. Tangco, MD
Cardiologist, Manila Doctors Hospital
Head, Cathlab, UP-PGH
Editor, The Filipino Internist
A couch potato spends much of his awake (and sleeping) time sitting or lying down, usually watching
television or video. Remote control in hand, a couch potato can be glued to his wide screen LED for
hours on end surfing the cable channels, or maybe watching a complete set of DVD’s downloaded from
the internet or bootlegged clear high def copies from some sidewalk hawker. It can be hours before he
gets up, and that’s just to pee. This slothful habit has now even extended to excessive video-gaming on
laptops and tablets, and not infrequently the couch potato just uses television vicariously while he plays
Bejewelled or Candy Crush on his iPad or as he chats with his friends on Facebook or Twitter. But the
classic couch potato also has the insatiable habit to munch and slurp chips and soda from 7-11, maybe a
bar or two of Magnum ice cream stick, or a latte from Starbucks plus a box of Krispy Kreme doughnuts if
he were to finish a complete season of Sherlock Holmes or a marathon of the Jason Bourne or Harry
Potter movies. And sometimes, it is couch potato day with the family so it becomes junk food fiesta
with boxes of pizza or a heaping bag of potato chips with matching dip, or buckets of greasy fried
chicken. This mental and physical inertia maybe the perfect panacea for a stressful week that just
passed by but this slothful habit if carried out daily, can be pathologic and lead to metabolic syndrome
and obesity.
Blame it on the genes others would say. Indeed, genetic mutation may have a role in making some
people lazier and less inclined to exercise. Researchers from Aberdeen University and the Chinese
Academy of Sciences theorize that a newly-found found 'coach potato gene', a mutation in SLC35D3 may
explain the slothful behavior. Mice with this gene mutation were less inclined to move about, ate a lot
and were obese. The SLC35D3 gene produces a protein which plays a key signaling role in the brain
dopamine system. The protein transports a dopamine receptor from inside the cell to the cell surface.
In their research, mice with this mutated gene had far fewer dopamine receptors on their brain cell
surfaces. Instead, the receptors were stuck within the cell rendering their signaling process
dysfunctional. But when they gave the mice a drug that acted on the dopamine signaling system, the
genetic defect could be overcome and the mice became more active and thinner. The researchers then
screened 400 overweight and obese Chinese patients with metabolic syndrome and found mutations in
the SLC35D3 gene in only two of them. The scientists hope that in the future, people with metabolic
syndrome may be screened to see if they have such a mutation. Maybe there are other genetic
mutations that we can research on.
Dr Gregory Steinberg of McMaster University in Ontario, Canada, looked at another potential genetic
excuse for couch potato behavior. His team has pinpointed the genes that produce an enzyme in
muscles during exercise called AMP kinase, which controls how food is converted into energy. Those
who generate large quantities of AMPK have more energy, whereas those with lesser amounts are likely
to tire almost immediately. His team found dramatic results in tests on two groups of mice, one bred
without the two suspected genes behind AMPK production. When given an exercise wheel, the mice
who still had the genes could go for 1km in just 20 minutes. By contrast, those without were ‘extremely
exercise intolerant’ and could achieve only a fast walk for around 40m before giving up. AMPK is
present in cells and is known to be responsible for boosting the number of mitochondria. This is the
first time scientists have demonstrated that AMPK is controlled by two genes and that removing them
hugely impairs our ability to exercise.
These findings has guided research in developing a personalized pill to reverse the genetic
predisposition: an exercise pill. Dr. Vihang Narkar from the University of Texas Health Molecular
Medicine is testing a drug that mimics the effects of exercise. The 'exercise pill' is being tested on mice
and is aimed specifically at people who are physically incapable of exercise, such as those in
wheelchairs. Dr. Narkar said the compound was administered to sedentary mice for about a month and
they were able to exercise up to 50 percent longer than untreated mice. Unfortunately for human
'couch potatoes' it could take a decade before the drug is approved for human use. And who knows, it
may go the way of fenfluramine and phentermine which were pulled out of the market because of
adverse affects on the pulmonary vasculature.
Inevitably it becomes a question of nature versus nurture, genetic predisposition versus behavioral
change. Dr. Steinberg claims exercise itself appears to stimulate the production of AMPK, and if couch
potatoes should overcome the inertia of inactivity, they can counteract their genetic predisposition. So,
junk the couch, close the television and laptop or tablet and get moving. Forget the genetic defect