Protein Links Gut Microbes, Biological Clocks, and Weight Gain

Fat calls with and without NFIL3

Caption: Lipids (red) inside mouse intestinal cells with and without NFIL3.
Credit: Lora V. Hooper, University of Texas Southwestern Medical Center, Dallas

The American epidemic of obesity is a major public health concern, and keeping off the extra pounds is a concern for many of us. Yet it can also be a real challenge for people who may eat normally but get their days and nights mixed up, including night-shift workers and those who regularly travel overseas. Why is that?

The most obvious reason is the odd hours throw a person’s 24-hour biological clock—and metabolism—out of sync. But an NIH-funded team of researchers has new evidence in mice to suggest the answer could go deeper to include the trillions of microbes that live in our guts—and, more specifically, the way they “talk” to intestinal cells. Their studies suggest that what gut microbes “say” influences the activity of a key clock-driven protein called NFIL3, which can set intestinal cells up to absorb and store more fat from the diet while operating at hours that might run counter to our fixed biological clocks.

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Snapshots of Life: A Flare for the Dramatic

lipid-covered water drop

Credit: Valentin Romanov, University of Utah, Salt Lake City

Oil and water may not mix, but under the right conditions—like those in the photo above—it can sure produce some interesting science that resembles art. You’re looking at a water droplet suspended in an emulsion of olive oil (black and purple) and lipids, molecules that serve as the building blocks of cell membranes. Each lipid has been tagged with a red fluorescent marker, and what look like red and yellow flames are the markers reacting to a beam of UV light. Their glow shows the lipids sticking to the surface of the water droplet, which will soon engulf the droplet to form a single lipid bilayer, which can later be transformed into a lipid bilayer that closely resembles a cell membrane. Scientists use these bubbles, called liposomes, as artificial cells for a variety of research purposes.

In this case, the purpose is structural biology studies. Valentin Romanov, the graduate student at the University of Utah, Salt Lake City, who snapped the image, creates liposomes to study proteins that help cells multiply. By encapsulating and letting the proteins interact with lipids in the artificial cell membrane, Romanov and his colleagues in the NIH-supported labs of Bruce Gale at the University of Utah and Adam Frost at the University of California, San Francisco, can freeze and capture their changing 3D structures at various points in the cell division process with high-resolution imaging techniques. These snapshots will help the researchers to understand in finer detail how the proteins work and perhaps to design drugs to manipulate their functions.

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Snapshots of Life: Fat (Tissue) Is Beautiful

Fat cells in 3D

Caption: Fat cells (red) surrounded by blood vessels (green) that supply them with nutrients.
Credit: Daniela Malide, National Heart, Lung, and Blood Institute; NIH

With all of today’s sophisticated microscopes, you’d think it would be simple to take high-magnification photos of fat—but it’s not. Fat tissue often leaks slippery contents, namely lipids, when it’s thinly sliced for viewing under a microscope. And even when a sample is prepared without leakage, there’s another hurdle: the viscous droplets of lipid contained in the fat cells block light from passing through.

So, it’s good news that one of NIH’s intramural scientists here in Bethesda, MD, has come up with a way to produce high-resolution, 3-D images of fat cells like the one you see above. Not only are these images aesthetically appealing, but they’ll be valuable to efforts to expand our understanding of this essential and much-maligned tissue.

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MicroRNA Research Takes Aim at Cholesterol

Illustration of artery partially blocked by a cholesterol plaque

Caption: Illustration of artery partially blocked by a cholesterol plaque.

If you’re concerned about your cardiovascular health, you’re probably familiar with “good” and “bad” cholesterol: high-density lipoprotein (HDL) and its evil counterpart, low-density lipoprotein (LDL). Too much LDL floating around in your blood causes problems by sticking to the artery walls, narrowing the passage and raising risk of a stroke or heart attack. Statins work to lower LDL. HDL, on the other hand, cruises through your arteries scavenging excess cholesterol and returning it to the liver, where it’s broken down.

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