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Study has implications for metabolic disease, insulin resistance, diabetes, and cardiovascular disease

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This is an oil red O staining of lipids in mouse liver: A, Normal, B, Fatty.
This is an oil red O staining of lipids in mouse liver: A, Normal, B, Fatty.

A new animal study shows how insulin controls the movement and storage of fat molecules in the liver and how a breakdown in this system could lead to non-alcoholic fatty liver disease and changes in circulating lipid levels associated with cardiovascular disease. Researchers from the Perelman School of Medicine at the University of Pennsylvania published their findings this week in the Journal of Clinical Investigation ( JCI ).

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"The production of triglyceride in the liver and its secretion into blood are closely linked to nutrient availability and insulin levels," said senior author Paul Titchenell, PhD, an assistant professor of Physiology and a member of the Institute for Diabetes, Obesity, and Metabolism. "After a meal, insulin tells the liver to package and secrete excess nutrients into triglyceride-rich lipid particles into the blood for use by the rest of the body."

After eating, glucose rises, which induces insulin release to control blood sugar levels by increasing glucose uptake and reducing glucose production by the liver. In addition to glucose regulation, insulin also controls blood lipid levels in part by increasing lipid synthesis, uptake, and storage in fat cells.

In the paper, the team demonstrated that mTOR complex 1 (mTORC1), a protein super-molecule made up of several smaller proteins, is essential for very low density lipoprotein (VLDL)-triglyceride production. VLDL-triglyceride molecules are exported by the liver and carry lipids to peripheral tissues. "This is important because in metabolic diseases associated with insulin resistance the liver makes more triglycerides, which leads to increased levels in the blood and eventually cardiovascular disease," Titchenell said.

In mice, the absence of mTORC1 in liver cells caused a build-up of triglycerides in the liver, thereby reducing circulating triglycerides. On the other hand, activation of mTORC1 depleted liver triglycerides and increased blood triglycerides. Titchenell identified an important cellular process controlled by mTORC1 and demonstrated that mTORC1 controls the production of another class of molecules called phospholipids, which are essential for the triglyceride export from the liver. Phospholipids are necessary to form a barrier around triglyceride molecules allowing for their export and transport throughout the body.

"In insulin-resistant disorders such as diabetes and obesity, hyperactive mTORC1 in liver leads to excess fat production and export," Titchenell said. "mTORC1 is what we want to target pharmacologically to decrease the risk of cardiovascular disease that is associated with obesity and diabetes. If we could affect mTORC1 in a balanced way, then maybe could help prevent non-alcoholic fatty liver disease and heart disease."

In the future, the researchers aim to unravel the precise mechanisms that mediate mTORC1's control of phospholipid synthesis to uncover novel drug targets with the goal of reducing the excess lipid burden during metabolic disease.

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Materials provided by University of Pennsylvania School of Medicine .

Journal Reference :

mTORC1 stimulates phosphatidylcholine synthesis to promote triglyceride secretion

In 2010, on my friend’s couch in Brooklyn, I noticed that Facebook was shipping user affiliation data over the wire to me, so I decided to store it. Facebook allowed apps to store data for which user permission was granted, but urged developers not to request or store more than it needed to operate. Putting affiliation data in the Cow Clicker database allowed me to provide leaderboard rankings by network, allowing my players to compete for clicks with their work colleagues or classmates.

That’s neither a terribly interesting feature nor a particularly wicked one. But because I stored the numerical identifiers for user affiliations, I still have them. , I could use a database-query tool called FQL, Facebook Query Language, to the details of those networks, and correlate them back to my users. Had I wanted to, I could have recombined that information with other data and used it for retargeting.

Cow Clicker’s example is so modest, it might not even seem like a problem. What does it matter if a simple diversion has your Facebook ID, education, and work affiliations? Especially since its solo creator (that’s me) was too dumb or too lazy to exploit that data toward pernicious ends. But even if I hadn’t thought about it at the time, I could have done so years later, long after the cows vanished, and once Cow Clicker players forgot that they’d ever installed my app.

This is also why Zuckerberg’s Best Prada Sport RoundToe Mary Jane Flats Discount Sneakernews Best Seller Online MMixL1Avt0
to the present controversy feels so toothless. Facebook has vowed to audit companies that have collected, shared, or sold large volumes of data in violation of its policy, but the company cannot close the Pandora’s box it opened a decade ago, when it first allowed external apps to collect Facebook user data. That information is now in the hands of thousands, maybe millions of people.

To be honest, I’m not even sure I know what the Facebook platform’s terms of service dictated that I do with user data acquired from Facebook. Technically, users could revoke certain app permissions later, and apps were supposed to remove any impacted data that they had stored. I doubt most apps did that, and I suspect users never knew—and still don’t know—that revoking access to an app they used eight years ago doesn’t do anything to reverse transmissions that took place years ago.

As Jason Koebler put it at Motherboard , it’s too late. “If your data has already been taken, Facebook has no mechanism and no power to make people delete it. If your data was taken, it has very likely been sold, laundered, and put back into Facebook.” Indeed, all the publicity around Facebook’s Cambridge Analytica crisis might be sending lots of old app developers, like me, back to old code and dusty databases, wondering what they’ve even got stored and what it might yet be worth.

Facebook’s laissez-faire openness surely contributed to the data-extraction free-for-all that’s playing itself out now via the example of Cambridge Analytica. But so did its move-fast-and-break-things attitude toward software development. The Facebook platform was truly a nightmare to use and to maintain. It was built like no other software system then extant, and it changed constantly—regular updates rolled out weekly. Old code broke, seemingly for no good reason. Some Facebook app developers were dishonest from the start, and others couldn’t help themselves once they saw the enormous volume of data they could slurp from millions or tens of millions of Facebook users. But many more were just struggling to eke out a part of their living in an ecosystem where people might discover them.

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