Inflammation resolution depends on changes to LPS

Even if you aren’t an immunologist, you are probably aware of the potent power of bacterial lipopolysaccharide, or LPS, to induce inflammatory responses. But how often do you think about the process by which this endotoxin is defanged so that inflammation can subside?

In a recent review in the Journal of Biological Chemistry, researchers led by Mingfang Lu of Fudan University update readers on the lipase that transforms LPS from stimulator to inhibitor of inflammation. You can read it here.

Cholesterol and membrane stiffness

A recent article in PNAS reports a biophysical investigation of cholesterol’s effect on unsaturated lipid membranes. While cholesterol is a known contributor to membrane fluidity and organization, its effects on bending, budding and other three-dimensional changes to membrane structure are less clear. Combining NMR, neutron spin-echo spectroscopy and molecular dynamics simulations, the authors show that cholesterol affects the rigidity of both saturated and unsaturated lipid bilayers.

Plasma membrane: no barrier to long-chain FFAs?

A flurry of recent papers in the Journal of Lipid Research discuss the molecular mechanism by which free long-chain fatty acids, or LCFAs, cross the plasma membrane.

While it was thought that LCFAs required fatty-acid binding protein CD36 as a transporter, recent work from James Hamilton’s lab at Boston University suggests that a putative CD36 inhibitor that supported this hypothesis in fact lacks specificity for CD36. Hamilton and colleagues, who have previously demonstrated fatty acid diffusion across a protein-free lipid bilayer, argue that this conclusively shows that diffusion is the main mechanism.

In a followup article, Glatz and colleagues argue that it may not be all over for CD36, instead suggesting a model that integrates active translocation and passive diffusion of LCFAs.

You can read more about the ongoing conversation in ASBMB Today.

Archaeologists use lipidomics to peer into the past

Julie Dunne, an analytical chemist at the University of Bristol uses GC–MS to examine the lipids embedded in the matrices of ancient shards of pottery.

“If you think about an unglazed ceramic pot, and if you had to put some milk in it, or even meat, and just boil it up, what you would actually see is fat globules floating on the top,” Dunne said. “Those globules of fat, lipids, absorb into the unglazed ceramic matrix during cooking.”

You can read more about how Dunne and colleagues are using ancient kitchenware to understand human evolution at ASBMB Today.

Mechanistic insights into allopregnanolone function

The neurosteroid allopregnanolone, which is derived from progesterone, received FDA approval last year as a treatment for postpartum depression. It’s thought to work more rapidly than other available treatments through positive allosteric modulation of GABA neurotransmitter receptors. However, closely-related allopregnanolone isomers have an opposite effect, inhibiting GABA(A) receptors.

In a recent study in eLife, Sugasawa and colleagues at Washington University in St. Louis investigated these opposite signaling effects. Using electrophysiology, binding assays and cryo-electron microscopy, they show that three structurally similar neurosteroids bind at different sites in the GABA(a) receptor, stabilizing it in open, resting or desensitized conformations and explaining the ligands’ variable effects on receptor activity. You can read the article here.

Double-membrane-spanning pore protein for viral replication

Positive-strand RNA viruses, including coronaviruses, have long been known to replicate their genomes within a vesicle wrapped, like the autophagosome, within a double plasma membrane. This raises the question of how newly-copied viral genomes reenter the cytoplasm to be packaged into new viruses. In a recent issue of Science, Wolff and colleagues report having discovered a pore-forming protein that spans both layers of the double-membraned vesicle, offering an escape route. You can read the article or a highlight by Unchwaniwala and Ahlquist..

Gene editing for lipid-linked diseases in macaques

At 2020’s virtual meeting of the International Society for Stem Cell Research, the company Verve Therapeutics announced that it had successfully used CRISPR editing to knock out PCSK9 and ANGPTL3 in the liver of adult monkeys. The modifications, co-founder and CEO Sekar Kathiresan reported, lowered blood triglycerides (in the case of ANGPTL3) or cholesterol (in the case of PCSK9) by more than 50%.

While underlying data have not yet appeared in a journal, you can read the press release here or a report by STAT news here.

How lipid droplets stay in shape

A recent Q&A with Andrew Greenberg in ASBMB Today traces the story behind his lab’s discovery of perilipin.

Perilipin (stained red) binds to the surface of lipid droplets (green) and functions as a dynamic scaffolding protein that controls entry and exit of lipids from the droplets.

While studying lipid droplet metabolsim in adipocytes, Greenberg’s lab discovered that perlipin is a crucial regulator of triglyceride metabolism.

Images in Lipid Research

A mass spectrometry image of the mouse brain shows distribution of different lipid species. Andres et al., JLR 2020

The Journal of Lipid Research recently launched a new article format focused on the contributions of imaging technologies to our understanding of lipid biology. These images in lipid research are brief articles focused on a single figure.

In an editorial introducing the series, associate editor Stephen Young wrote, “We anticipate that JLR’s Images in Lipid Research series will be fun and informative for practicing scientists.”

You can browse the images in lipid research here.