Metabolism, Regulation, and Cancer

Occasional posts inspired from teaching. I'm a biology professor, with a PhD in molecular biophysics and biochemistry, and three decades of active research experience.

[metabolismandregulation]

"Correlation is not causation" has been fetishized

The quote above is from The Book of Why, a fantastic new book from Judea Pearl, one of the leading lights of causal inference. His other books are more mathematical, but this accessible text is written for a general audience.

The fetishization of "correlation is not causation" is very real, ubiquitous on Tumblr, and plagues discussion of both healthy metabolism and metabolic pathologies.

"Correlation is not causation" should be the start of discussion, not its end.

[bigfatscience]

is it possible for mental exercise to be physically taxing? i notice that when i'm at school i get hungry a lot faster even without doing any ohysical activity. same with studying at home. o_o

Dude, your brain consumes like 20% of your daily energy intake! And that is why depression, anxiety, lack of focus, irritability and other mental functions all suffer when you don’t eat enough. The brain needs fuel to function, and if you use your brain more – thinking, regulating, processing – then you need more fuel.

[metabolismandregulation]

This is a misunderstanding. While it’s true that the brain consumes a huge amount of energy for its size, the evidence is that mental exercise itself doesn’t place much of an additional metabolic burden on the brain. Here is a good link on the subject.

The other activities or patterns often associated with a feeling mental exhaustion --- lack of sleep, stress, test anxiety, etc. --- have well-established metabolic consequences. So while the feeling of mental exhaustion is real, it's probably not the mental activity itself that's causing it.

[metabolismandregulation]

The Belly Fat Battle

A wider waist is dangerous for reasons we don’t fully grasp

This is an interesting and accessible article about belly fat

[metabolismandregulation]

A New Acupuncture Study Is One of the Worst Studies I Have Ever Seen | RealClearScience

A new meta-analysis published in PLoS ONE comparing acupuncture and drugs for the treatment of chronic constipation is one of the worst studies I have ever seen. Chinese researchers from Longhua...

Meta-analysis can be used to deceive as well as to inform. This meta-analysis of acupuncture versus other constipation treatments is downright terrible and is a great example of misleading through pseudoscience.

[metabolismandregulation]

Are G.M.O. Foods Safe?

In the decades since the first genetically modified foods reached the market, no adverse health effects among consumers have been found.

Spoiler alert: yes

[metabolismandregulation]

So much ignorance would vanish if everyone wore a continuous glucose monitor for a week

I used one this semester teaching a class of over a hundred university students. It’s a remarkable tool for teaching, and of course life-changing for many diabetics. But its also remarkable how much a single biosensor can improve a metabolically healthy person’s understanding of satiety, hunger, blood sugar “crashing”, and just body awareness. Strategies like intuitive eating emphasise listening to the body, but having the CGM data makes that “listening” exercise a lot more grounded. At least it did for me.

[feedyourselfcheaply]

High fructose consumption and insulin resistance

First off, I wanted to clarify my understanding here: countless studies have shown that when consumed in excess, fructose can lead to insulin resistance as well as obesity; however, from the studies I have read, most tests only considered/accounted for the kind of added fructose in highly processed junk food. So my question is: would an excessive consumption of fructose from fruit have the same effect (eating an extreme amount of fruit)?

Also: I know that glucose and fructose are metabolized differently on the body (glucose bypasses the liver and is used by the body, fructose is easily broken down in the liver), but could someone give me a simple explanation as to how fructose consumption can lead to greater fat storage/gain than glucose?

Found here

[metabolismandregulation]

Digested dietary sugars are released into the portal vein, which drains to the liver. Your write “fructose is easily broken down in the liver”, but it’s more than that: fructose is almost exclusively broken down in the liver in humans. So the dietary sugars from the portal vein go to the liver, and the liver has to deal with the fructose. If the fructose is digested rapidly, the fructose concentration in the blood goes way up, but doesn’t affect insulin signaling (unlike glucose). 

Fructose taken up by the liver can be metabolised in one of three ways: to glucose (for release into the blood), to glycogen (for storage in the liver), or to fatty acids (for release into the blood as VLDL particles). If the blood glucose is already high, and the liver glycogen is already at capacity (both common in a well fed state), then the fructose is converted to fatty acids and triglycerides, and packaged into VLDLs. So dietary fructose is lipogenic: it leads to lipid (fat) synthesis, and that fat gets stored in adipocytes (fat cells).

However, because the liver is solely responsible for fructose metabolism, excess dietary fructose puts stress on the liver and leads to buildup of fat not just everywhere in the body, but in and around the liver itself. The lipid droplets that accumulate in the liver from this process are known as “non-alcoholic fatty liver disease”, or NAFLD. When most severe, this is called “non-alcoholic steatohepatitis” (NASH), and can lead to cirrhosis and liver failure. NAFLD is the most common type of liver disease in economically developed  countries.

NAFLD/NASH are very closely related to insulin resistance in the liver. There is excellent evidence from Gerald Shulman’s lab at Yale University that the lipid droplets in the liver from NAFLD (more specifically the diacylglycerides from the lipid droplets) cause insulin resistance.

Now, what about fruits? Biochemically, fructose is fructose. However, because whole fruits are digested more slowly than fruit juices or many processed foods with sweeteners, the digested fructose will be released more slowly into the bloodstream, putting less stress on the liver. But excess fructose from any source goes through the same processes.

[currentsinbiology]

Philadelphians Drink Less Sugary Soda, More Water, After Tax

Researchers at Drexel University surveyed residents of Philadelphia both before and after a 1.5-cent-per-ounce tax on sweetened drinks took effect. They also surveyed people in three other cities that don’t have a beverage tax. The researchers found Philadelphians were about 40 percent less likely to drink sweetened beverages daily after the tax went into effect, compared with people in the other cities.

At the same time, Philadelphians’ consumption of bottled water, which is not taxed, increased. The findings are published in the American Journal of Preventive Medicine.

It’s not clear whether a decline in consumption of sweetened drinks linked to the tax will lead to any measurable health benefit. “It will take much longer to observe an impact on health outcomes,” says Zhong. “Many other factors, such as beverage substitutions and overall diet quality, need to be evaluated” as well.

[metabolismandregulation]

Where does insulin resistance come from? Part 1: the Randle hypothesis

Insulin resistance -- the inability of cells to fully utilise insulin signals even though insulin is present -- is a requirement of Type 2 Diabetes. How does insulin resistance arise?  One theory was put forward by Randle and colleagues over 50 years ago, but remains influential [1].  The idea stems from a cycle (shown above, from [2])  that regulates levels of glucose and fatty acids by competition for oxidation. In the figure, the circulating part is the in the middle (blue) and the two key tissue types are on either side. 

Adipose tissue (right) is used for fat storage. When insulin signals  adipose cells (adipocytes), glucose is used as fuel and fat synthesis. This normally inhibits the breakdown of stored fat, since fuel is abundant.

Muscle cells (left) can use glucose or fat for fuel. Insulin also signals muscle cells to increase glucose uptake and use as fuel. But long chain fatty acids (LCFA) inhibit the use of glucose for fuel in the muscle. If a muscle cell is oxidising fuel, it can use either glucose or fatty acids; there is competition between the processes and some substrates.

How does the presence of fatty acids inhibit oxidation of glucose? A major part of the Randle model is that an abundance of free fatty acids undergoing fatty acid oxidation leads to buildup of citrate, which inhibits key enzmes in the glucose transport and glycolytic pathways. Effectively, excess fatty acids lead to a form of glucose intolerance and, possibly eventually, insulin resistance.

So that’s a few highlights of the model.  As I indicated, it’s very influential, and it’s likely to be the model that’s taught in a university or medical school class that covers insulin resistance.  

I’ll cover evidence for and against the Randle hypothesis (and other models of insulin resistance) in future posts.

[1] Lancet. 1963 Apr 13;1(7285):785 9. (link) [2] Am J Physiol Endocrinol Metab. 2009 Sep; 297(3): E578–E591. (link)

[fieldnotesfarmer]

The first step to making my interpretive panel is creating a rough drawing and layout. This is version 1, and I already have a list of changes to make. I’ve found the design aspect of my work to be just as fun (and just as important) as the illustration side. Back to the drawing board!

[metabolismandregulation]

Lovely

[metabolismandregulation]

National Cancer Institute on Twitter

“There is consistent evidence that higher amounts of body fat are associated with increased risks of a number of cancers: https://t.co/9BDoGzRiuh #aacr18”

This is a good overview of the current state of knowledge about the relationship between cancer and obesity, from the US National Cancer Institute  

[gottaworkhardforit-deactivated2]

50 Years Ago, Sugar Industry Quietly Paid Scientists To Point Blame At Fat | NPR

In the 1960s, the sugar industry funded research that downplayed the risks of sugar and highlighted the hazards of fat, according to a newly published article in JAMA Internal Medicine.

The article draws on internal documents to show that an industry group called the Sugar Research Foundation wanted to “refute” concerns about sugar’s possible role in heart disease. The SRF then sponsored research by Harvard scientists that did just that. The result was published in the New England Journal of Medicine in 1967, with no disclosure of the sugar industry funding.

The sugar-funded project in question was a literature review, examining a variety of studies and experiments. It suggested there were major problems with all the studies that implicated sugar, and concluded that cutting fat out of American diets was the best way to address coronary heart disease.

The authors of the new article say that for the past five decades, the sugar industry has been attempting to influence the scientific debate over the relative risks of sugar and fat.

“It was a very smart thing the sugar industry did, because review papers, especially if you get them published in a very prominent journal, tend to shape the overall scientific discussion,” co-author Stanton Glantz told The New York Times.

Read more.

[lolmythesis]

I studied a protein for 4,5 years nobody ever studied before. Now I know why.

Biochemistry, University of Hohenheim

[metabolismandregulation]

Real science proceeds by argument

Many students learn science by memorising content and writing lab reports. In most lab classrooms, all the students are working on the same problem, and students are working to get the “right” answer.

Actual scientific research doesn’t proceed like that at all. 

Scientists argue with each other over models, interpretations, and even data all the time. The joy of doing research is not in being right every time, but in getting better at explaining the world over time through a process that usually works. Now, I don’t have any illusions about science being perfect or quickly self-correcting. (For what it’s worth, I’m absurdly familiar with anti-science literature.) But science still beats the alternatives.

The process of argument is really evident in the Point-Counterpoint I posted earlier on the obesity paradox in cancer. (Link to the journal)

[metabolismandregulation]

Camilla Cavendish, the initiator of the UK’s tax on sugar, says it’s time to start treating it like nicotine

This is such an interesting article, but the FT doesn’t allow a proper link to it from Tumblr. 

[roberteshelman-hakansson]

The Joys of Reading — and Writing — About Science

At various stages in my journalism career, I’ve been a war reporter and a political reporter in the US and abroad. I’ve even written about visual art and icons of entertainment. These days, when I’m not editing Seeker, I write about climate change and environmental issues.

As difficult as those settings or topics may be, I’ve often found the most challenging writing — the task of transforming a blank page into a story — to be science writing. The concepts are often fantastical and the result of rarified knowledge from disciplines like chemistry, neuroscience, and astrophysics. Each of those fields, as well as countless others, are peering more deeply into — and thinking more complexly about — floral and fauna, the human mind, the deepest reaches of the cosmos, and just about everything in between.

Despite years of writing about science and editing many really talented science writers, the task of a science journalist can often feel daunting. (I try to not lose sight of the fact that I’m a) a journalist with a job in a very unfavorable job market and b) one working in the exciting field of science.) Even an advanced degree in science journalism often leaves me longing for many more years in an academic setting in order to feel more comfortable when speaking with researchers or reading a journal article.

With all that in mind, I read this wonderful passage about black holes, written by The New York Times’s Dennis Overbye in his obituary of Stephen Hawking, the iconic astrophysist who died last night at the age of 76. The passage was a reminder of how difficult the task of science writing can be, but also how tremendously rewarding it can feel as a writer, as well as a reader.

Here’s the passage that caught my eye:

By necessity, he concentrated on problems that could be attacked through ‘pictures and diagrams,’ adopting geometric techniques that had been devised in the early 1960s by the mathematician Roger Penrose and a fellow Cambridge colleague, Brandon Carter, to study general relativity, Einstein’s theory of gravity.

Black holes are a natural prediction of that theory, which explains how mass and energy ‘curve’ space, the way a sleeping person causes a mattress to sag. Light rays will bend as they traverse a gravitational field, just as a marble rolling on the sagging mattress will follow an arc around the sleeper.

Too much mass or energy in one spot could cause space to sag without end; an object that was dense enough, like a massive collapsing star, could wrap space around itself like a magician’s cloak and disappear, shrinking inside to a point of infinite density called a singularity, a cosmic dead end, where the known laws of physics would break down: a black hole.

Einstein himself thought this was absurd when the possibility was pointed out to him.“

That, in my estimation, is wonderful science writing. Overbye conveys very specialized and abstract physics in a way that’s evocative, and a layperson is likely to easily understand.

It also made me recall why writing by the New Yorker’s John McPhee can be so enjoyable and informative at the same time, whether reading his descriptions of deep geological time or relating the movements and causes of a California mudslide.

Hat tip to them, and to my fellow science journalists out there.

[metabolismandregulation]

Both kinds of science writing -- writing about science and writing science -- are indeed hard. Like @robertseshelman, I read Overbye’s obituary about Hawking and was struck by that passage. I went back and read Hawking’s original paper on Hawking radiation, which is short and beautifully written. Given the difficulty of the underlying mathematics, and that Hawking had to do the calculations largely in his head, it’s remarkable that is was written at all, but still more remarkable that it is written so well.

Recently I was asked to contribute a book chapter to a scientific volume. The topic was close to, but not exactly in, my area of research: it was close enough that an outsider probably wouldn’t see any difference, but a specialist would recognise immediately that it was not in my wheelhouse. That chapter wound up being one of the more difficult pieces of writing I’ve done, but it was so much fun.

I wonder if we who teach science in university don’t use science journalism enough.

[metabolismandregulation]

Omega-3 Supplements Don’t Protect Against Heart Disease

“Carefully done trials provide no support for the hypothesis that fish oil supplements help,” the senior author of a new study says.

Like a lot of people, I take omega-3 supplements. One reason is for cardiovascular health, but it appears there is no evidence for that recommendation.