September 2019 | Kao and colleagues report in the Journal
of Lipid Research that selective pressure from chemotherapeutic treatment
affects sphingolipid metabolism in leukemia cells. Cells that were most
resistant to a standard chemotherapeutic regimen also showed altered
sphingolipid metabolism, suggesting that drug resistance may depend on mitochondrial
adaptation. To learn more about sphingolipid metabolism, read the Journal of
Lipid Research’s recent virtual issue on
August 2019 | An enduring question in studies of the origin of life
is how the first lipid membrane was assembled, especially given that it
probably happened in a salty aqueous solution inhospitable to lipids. New
research in the Proceedings of the National Academy of Sciences suggests that
prebiotic amino acids can bind to and stabilize protocellular membranes. Read more.
August 2019 | A virtual issue of the Journal of Lipid Research
collects research into the pathophysiology of lipoprotein(a). This
lipid-binding protein is linked to atherosclerosis and other cardiovascular
diseases, but how it’s assembled, secreted and cleared from the blood are still
mysterious. Read the issue,
assembled by JLR Junior Associate Editor Gissette Reyes-Soffer, to learn more
about Lp(a) and what questions remain.
July 2019 | One puzzling feature of gangliosidoses is that often,
secondary complex lipids will accumulate even in the absence of mutations
to their turnover pathways. A study from the Sandhoff lab at Bonn University,
led by Susi Anheuser, sheds light onto the mechanism for secondary
accumulation. Lysosomal lipid degradation enzymes’ activity is affected by the
surface charge of lysosomal intraluminal vesicles, and primary lipid-turnover
disorders can affect that surface charge. The study appears in the Journal
of Lipid Research; read a summary in ASBMB Today.
July 2019 | Researchers led by Scott Summers report in Science that
knocking down the ceramide desaturase DES1 in mice on a high-fat diet improves
insulin resistance. The enzyme converts dihydroceramide, which has a saturated
side chain, to ceramide, which is unsaturated. Read the article here.
May 2019 | Lipid researchers take center stage in a feature in the
May issue of ASBMB Today that explores the history of lipidomics and the
challenge of establishing reproducible methods and reference measurements to
enable discovery and use of lipid biomarkers. Read the article here.
May 2019 | Esler and colleagues from Pfizer’s cardiovascular
research unit and the University of California show that, unlike model
organisms used to study sebum production, humans generate more than 80% of the
lipids in this waxy skin secretion through de novo lipogenesis. Sebum
production is higher in people with severe acne. By targeting acetyl-CoA
carboxylase, or ACC, with an orally available inhibitor, the researchers
reduced participants’ sebum excretion by half. The authors propose that ACC may
be a promising therapeutic target to combat acne. (Pfizer is also developing an
ACC inhibitor to treat nonalcoholic steatohepatosis.) The work appears in Science Translational
Lipid transport: all it takes to reprogram neutrophils
April 2019 | Immune dysregulation is an important part of the
cancer landscape: better evasion or dampening of immune responses leads to
worse clincal outcomes. Veglia et al. report that pathologically activated
neutrophils in cancer overexpress fatty acid transport protein 2, or FATP2. The
protein, expressed in response to a growth factor, enables the neutrophils to
take up more arachidonic acid and produce more prostaglandin. Pharmacological
inhibition or genetic deletion of FATP2 in these cells slowed tumor progression
in mice. The study appears
April 2019 | One weapon in the skin’s arsenal against invaders
is an unsaturated 16-carbon fatty acid called palmitoleic acid. Subramanian et
al., investigating a Staphylococcus aureus fatty acid desaturase called OhyA,
discovered that the protein is used to detoxify sebum lipids. Read
March 2019 | Researchers using the hybrid mouse diversity
panel developed in LRD member Jake Lusis’s lab to understand how lipid
dysregulation leads to liver dysfunction found that lipid abundance appears to
correlate with certain proteasomal proteins. Read more.
December 2018 | Working in yeast and cultured neurons, a team of
researchers has shown that inhibiting stearoyl-CoA desaturases can reduce toxic
aggregation of alpha-synuclein, the lipid-binding protein that accumulates in
Parkinson’s disease. Read the work here.
October 2018 | You’ve heard of paleogenomics, and maybe
paleoproteomics; now, researchers from around the world have used mass
spectrometric analysis of lipid biomarkers fossilized in an Ediacaran fossil to
establish its phylogeny. Their paper appeared
in Science in September.
August 2018 | The August cover article of the Journal of Lipid
Research features a newly-reported, ultra-long-chain hydroxy fatty acid that
occurs naturally in the lipid layer of human tears. Prior experiments in
Langmuir troughs have demonstrated that ultra-long-chain lipids, known as
OAHFAs, are required to keep the lipid layer optically clear. Hancock and
colleagues characterized the 50-carbon lipid, OAHFA 50:2, and developed a
synthesis strategy. Read
June 2018 | Plasmalogens are unusual phospholipids, characterized
by an ether next to an alkene, a group known as a vinyl ester, that links the
head group and one fatty acid tail. Degradation of plasmalogens can produce
arachidonic acid, an important precursor to the eicosanoid family of signaling
molecules; but how plasmalogens are cleaved was unknown.
Researchers in Richard Gross’s lab at Washington University in St. Louis recently
found that mitochondrial protein cytochrome C can cleave the vinyl ester.
Because the cytochrome’s plasmalogenase activity is activated by oxidative
stress, the finding hints at a link between mitochondrial oxidative stress and
inflammation in conditions like ischemia and amyloidosis. Read the original
JBC article here, or a Research Highlight here.
August 2017 | Ken Hsu, assistant professor of chemistry at the
University of Virginia, and Caroline Franks, a graduate student in the Hsu lab,
discuss their research on diacylglycerol kinases (DGKs). Franks is the first
author on the paper “The Ligand Binding Landscape of Diacylglycerol
the paper in the journal Cell Chemical Biology.
June 2017 | Kyle Korshavn, a postdoctoral researcher in Ayyalusamy Ramamoorthy’s lab at the University of Michigan, was first author on a paper reporting how pathologically thin lipid bilayers affect amyloid-β aggregation and how pathological lipid oxidation may contribute to Aβ cytotoxicity. Read Korshavn’s paper in the Journal of Biological Chemistry. or watch a video of Korshavn talking about his work.
January 2017 | Researchers have been discussing for many years
the role of the lipid matrix in regulating the activity and the organization of
membrane proteins. A variety of effects have been singled out and studied
qualitatively and quantitatively in model systems. However, the applicability
of those results to living cells is — in many cases — unsatisfactory. Read the rest of this
“Lipid News” article by Eva Sevcsik and Gerhard J. Schütz in ASBMB Today.