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A metabolic master switch underlying human obesity

131 点作者 apas超过 9 年前

11 条评论

JamesBarney超过 9 年前
The phrase that being overweight is &quot;simply calories in vs calories out&quot; is both trivially true and completely unhelpful.<p>It&#x27;s similar to thinking we have solved poverty. People living in poverty should spend less and make more. Problem solved.<p>The much more interesting questions are<p>1. Why does it take some people more food to reach the same level of satiety as others?<p>2. Why do some people&#x27;s bodies burn off excess calories through things like non-exercise activity thermogenesis and other store it as fat?<p>3. Do different types of food effect long term satiety? By changing what we eat can we effect our weight in the long term?<p>4. How does the body increase hunger and turn off self-control when there is reduced food intake?<p>The only known &quot;solutions&quot; we currently have to obesity are dieting and exercise. The problem is the long term efficacy rate of dieting is around 5%. If dieting were a drug it would never pass FDA approval for effectiveness. Exercise has only modest effects and is probably more effective as preventing weight gain than causing weight loss.<p>We still have so much more to learn. We are just at the beginning of figuring out the causes and solutions to this issue.
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gwern超过 9 年前
The paper is: &quot;FTO Obesity Variant Circuitry and Adipocyte Browning in Humans&quot;, Claussnitzer et al 2015; fulltext: <a href="http:&#x2F;&#x2F;www.nejm.org&#x2F;doi&#x2F;full&#x2F;10.1056&#x2F;NEJMoa1502214" rel="nofollow">http:&#x2F;&#x2F;www.nejm.org&#x2F;doi&#x2F;full&#x2F;10.1056&#x2F;NEJMoa1502214</a>
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balabaster超过 9 年前
It would be interesting if they could find some food that flipped this on... clearly obesity is reaching epidemic proportions and there appears to be some correlation between this and the consumption of processed foods. It would be interesting to figure out if there&#x27;s something in our food that is flipping the switch to lead down that path. Now that we have some (apparently) credible evidence correlating these switches with obesity, it would be handy to be able to see what to avoid to prevent this switch from being triggered... also if there&#x27;s something that&#x27;s not in control of the drug companies that we could eat to flip it back.
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PaulHoule超过 9 年前
It is better to think of this as a target of intervention with drugs and other therapies than as a &quot;gene therapy&quot; product.<p>The article says that the key process is enabling thermogenesis:<p>&quot;Follow-up experiments showed that IRX3 and IRX5 act as master controllers of a process known as thermogenesis, whereby adipocytes dissipate energy as heat, instead of storing it as fat. Thermogenesis can be triggered by exercise, diet, or exposure to cold, and occurs both in mitochondria-rich brown adipocytes that are developmentally related to muscle, and in beige adipocytes that are instead related to energy-storing white adipocytes.&quot;<p>If you apply all the methods in terms of exercise, diet, and exposure to cold, you are pushing this switch the right way -- some people might need harder pushing than others.
nlh超过 9 年前
Thought exercise:<p>Extend a finding like this out to the (il)logical conclusion 5, 10, 15 years out -- we figure out what causes the body to store fat, we develop the wonder drug that everyone&#x27;s been waiting for that &#x27;flips the switch&#x27; (even in otherwise healthy people), and suddenly everyone has 7.5% bodyfat and weighs exactly as much as they want to.<p>And then....what? Well from a macro scale, I think some things get better -- overall population health goes up, obesity&#x2F;fat-related diseases go down. But does heart disease? I wonder if it goes up -- if everyone looks like they&#x27;ve wanted by shutting off the body&#x27;s fat stores, does the motivation to do cardio go down for some people? (Cardio has huge benefits for things way beyond your bodyfat, but that won&#x27;t stop a big chunk of the population from giving up on it.)<p>And from a purely superficial angle -- now everyone who wants one has a &quot;ripped&quot; body. But some guys are still bald, or have back hair, or or or. We&#x27;ll still find a way to feel bad about ourselves, even with six-packs.<p>Thoughts?
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rubicon33超过 9 年前
&quot;By editing a single nucleotide position using the CRISPR&#x2F;Cas9 system — a technology that allows researchers to make precise changes to a DNA sequence — the researchers could switch between lean and obese signatures in human pre-adipocytes.&quot;<p>How far off are we from therapy using the CRISPR&#x2F;Cas9 system? I would imagine that while it&#x27;s easy to edit the sequence for cells in a petri dish, editting the cells of an entire organism (human) is not likely to happen in our lifetime?
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s3nnyy超过 9 年前
&gt; “Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual’s metabolism”<p>People might misunderstand this to justify laziness. I have an obese co-worker, who likes to eat several hundred grams of chocolate along with soft-drinks daily. He always quotes genetics to counterargument my elaborations on the first law of thermodynamics.
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jobu超过 9 年前
<i>&quot;The paper is a tour de force, according to Evan Rosen, a professor of medicine at Harvard Medical School who was not involved in the research.&quot;</i><p>That&#x27;s some pretty high praise.<p>Also, it wasn&#x27;t entirely clear to me if they&#x27;re already testing this on humans. They mentioned using the CRISPR&#x2F;Cas9 to manipulate genes in human cells, is that just donated human tissue?
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untilHellbanned超过 9 年前
What I don&#x27;t like is how the press and often scientists make every paper seem like something was newly identified. With no disrespect to the authors of this particular study, they didn&#x27;t &quot;unveil a new pathway&quot;. Several previous works over the past decade have honed in on this exact &quot;master switch&quot;.<p>E.g.,<p>Identification of FTO as relevant to obesity (2007): <a href="http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;17434869" rel="nofollow">http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;17434869</a><p>Connection of FTO and IRX3 (2014): <a href="http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;?term=24646999" rel="nofollow">http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;?term=24646999</a>
grok2超过 9 年前
In this context, this report from 23andMe is interesting....perhaps old news: <a href="http:&#x2F;&#x2F;blog.23andme.com&#x2F;wp-content&#x2F;uploads&#x2F;2015&#x2F;03&#x2F;5-N8XiOLkGIgydwX_SS-IQ_23-08_Genetic_Associations_With_Traits1.pdf" rel="nofollow">http:&#x2F;&#x2F;blog.23andme.com&#x2F;wp-content&#x2F;uploads&#x2F;2015&#x2F;03&#x2F;5-N8XiOLk...</a>
forrestthewoods超过 9 年前
I found the master switch. It&#x27;s called self-responsibility.
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