FINALLY!

Scientists have found a way to let you eat ANYTHING

you want without gaining weight
By: Rowling Zhan

©Bokeh-licious Available from: https://flic.kr/p/ad9xk4

Imagine waking up one day with the superpower to enjoy burgers, macaroons, and fried
chicken while still keeping your abs and thigh gaps in perfect shape …

That’s when you know you are still dreaming!

Insane, right? But in fact, this magic has already become a reality. Scientists have
successfully found a pill that can alleviate your guilt having that pepperoni pizza with extra
cheese at 1 am.

In 2018, Chinese researcher, Dr. Feng Zhang, and his colleagues from Yale University
unveiled the mystery of the fat-uptake mechanism of the human body and discovered the key
to manipulate it1. In their experiments, two groups of five-week-old mice were studied.
Group A (the experimental group) had two specific genes in their intestines removed, while
Group B (the control group) did not undergo this procedure. Identical high-fat diets (HFD)
were fed to the two groups. In the end, it was found that the mice in Group A barely gained
any weight, whereas the littermates in Group B doubled their body weight after 16 weeks of
HFD feeding.

To understand how and why this happened, let’s first review this Biology 101.

How are fats absorbed by our body?

Think about our body as a huge pastry factory and fat molecules as donut doughs. When we
pass a big blob of dough into the stomach chamber, a few workers called digestive enzymes
would first approach the dough and cut it up into smaller round pieces. Then, each piece of
dough is sent to the pond of bile for coating and glazing. After sprinkling with cholesterol
and vitamins, these doughs should be ready to pass through pipes of blood capillaries and
enter the lymphatic chambers where they will be stored as energy.

However, there is one more step before that. Unlike their cookie friends who have petite body
figures and can easily squeeze through the thin slits between the walls of capillaries, these
donut pieces are quite large. Therefore, they have to use a separate VIP pipeline called the
lacteals in order to reach the energy storage site. Lacteals are finger-like structures on the
small intestine wall that pipe the fatty donut doughs to the lymphatic chambers. As the
lacteals have wider slits in them, the dough can easily enter and move down to the lymphatic
chambers to be stored as long-term energy sources for the factory.

Knock out the key protein

 Now that we understand how fats are transported and stored in our body, what exactly did
the Yale scientists do to control the process?

The key to weight control is within the genes. In the experiments, Dr. Zhang and his team
removed two proteins, Flt1 and Nrp1, from the mice in Group A. These two proteins are like
the security guards at the slits of the lacteal tubes. As the fatty molecules can pass down the
tubes and later be stored as energy only when the gates of the slits are open, by removing the
two proteins, it is like putting the security guards to sleep. For safety reasons, these very
responsible security guards would close the gates before they go to sleep. Now, no one is
opening the lacteal gates for the fatty doughs, and they cannot pass into the lymphatic
chamber as a result.

As the gateway to energy storage is blocked, the fats you take in will, therefore, be excreted
outside of the body directly. This explains why mice in the experimental group did not gain
much weight despite being fed with high-fat meals.

 Doctor, could you knockout my fatty proteins, please?

 Diet-induce obesity has become increasingly prevalent around the world in recent years,
including Hong Kong2. As we have seen earlier from the experiment, Dr. Zhang’s team did
successfully stop the mice from gaining weight by zippering their lacteals. Since the scientists
have already figured out the fat absorption mechanism, wouldn’t that be nice if they can
perform this technique on people, especially obese patients, to limit their lipid uptake?

Unfortunately, so far it is not quite the case. There have been vigorous ethical debates about
the feasibility of human genome editing. Even though the knockout procedure worked well
on mice, the current state of technology has not yet reached the point that allows scientists to
genetically modify real human bodies.

Modifying the genome of the human body is a much more complex project compared to that
of mice. Changing the genetic information and protein composition in the human body may
likely trigger unintended mutations or cause negative side-effects on intestinal health3.
While limiting the absorption of fat, zippering the lacteals can also obstruct the intake of
some other micronutrients that are important to our health. Moreover, blocking the lacteals
may also interfere the fluid balance of the body and the transportation of other immune cells,
as argued by some scientists.

New hope for weight control?

So, is that the end of the story? I thought you said that I could eat anything without worries!

Relax. Scientists have got you covered! Although sliming by knockout doesn’t work in our
case, scientists have figured out another way. Dr. Zhang and his team have found a FDA-
approved drug called ROCK (Rho-kinase, cool name for a protein right) inhibitor that serves
the same purpose. Originally designed for treating eye diseases, the ROCK inhibitor was also
found effective in regulating the transportation of sugar and improving the body metabolism.

The rationale behind removing the two “fatty proteins” Flt1 and Nrp1 was that it switches off
the proteins that are responsible for holding the lacteal slits open. Surprisingly, this function
can be mimicked by the ROCK inhibitor as well4. Once those guard proteins are deactivated,
the lacteals can be pulled together and zippered up. Zhang and co. experimented their guess
with a ROCK inhibitor named Y27632, which successfully tightened the lacteal slits and
stopped the absorption of the fatty molecules.

Good news right? Even better news is that the ROCK inhibitor has actually been made into
pills for purchase and were put in clinical use already. Although studies have shown that the
pills can control weight gain, do not abuse them as they also carry side-effects5 like liver
malfunction and hypotension (i.e. low blood pressure).

What’s next?

 Being the first-ever scientific research to explain the important role of lacteals in fat
transportation and absorption, Dr Zhang’s findings have opened a new avenue for
investigating obesity control and body weight regulation.

Although more comprehensive clinical trials on the effectiveness and drawbacks of using the
ROCK inhibitor, for instance, as a means of combating obesity is needed, understanding the
lacteal mechanism provides a starting point for further research in this field.

Science does provide a lot of shortcuts and convenience in daily life. While staying tuned for
new scientific updates on safer and more promising ways to zip up obesity, why don’t we
start from zipping up the bags of Lay’s today?

References

1. Zhang F, Zarkada G, Han J, Li J, Dubrac A, Ola R, Genet G, Boyé K, Michon P,

Künzel SE, et al. Lacteal junction zippering protects against diet-induced
obesity. Science. 2018 Aug [accessed 2018 Nov 25]; 361(6402):599-603.
https://science.sciencemag.org/content/361/6402/599.full.
 2. Su X. Half of Hongkongers over 15 now overweight or obese, damning government
health study reveals. South China Morning Post Online. 2017 Nov 27. [modified 2018
Jul 20. accessed 2018 Dec 1]. https://www.scmp.com/news/hong-kong/health-
environment/article/2121831/half-young-hongkongers-now-overweight-or-obese?
utm_source=edm&utm_medium=edm&utm_content=20171128&utm_campaign=scm
p_today&emarsys=1&sc_src=email_2086072&sc_llid=58501&sc_lid=147434851&s
c_uid=7J3EGNONN1.
3. National Human Genome Research Institute (NHGRI). Knockout Mice Fact Sheet.
2018. [accessed 2018 Dec 2]. https://www.genome.gov/about-genomics/fact-
sheets/Knockout-Mice-Fact-Sheet#al-1.
4. Liao J, Seto M, Noma K. Rho Kinase (ROCK) Inhibitors. Journal of Cardiovascular
Pharmacology. 2007 [accessed 2018 Nov 28]; 50(1):17-24.
http://journals.lww.com/cardiovascularpharm/Fulltext/2008/03000/Long_term_Inhibit
ion_of_Rho_kinase_Ameliorates.15.aspx.
5. Huang H, Lee D, Zabolotny J, Kim Y. Metabolic actions of Rho-kinase in periphery
and brain. Trends in Endocrinology & Metabolism. 2013 Aug [2018 Nov 28]; 24(10):
506-514.
https://www.researchgate.net/publication/255788874_Metabolic_actions_of_Rho-
kinase_in_periphery_and_brain. DOI: 10.1016/j.tem.2013.06.003.