Journal News

From the journals: JLR

Isha Dey
February 11, 2020

We offer a selection of papers recently published in the Journal of Lipid Research. Topics include interactions of the endocannabinoid pathway with the gut microbiome, a novel way to detect turnover of an essential acid in the brain and inhibiting fatty acid oxidation to treat insulin resistance.

Gut feeling: The endocannabinoidome and intestinal microbe connection

The endocannabinoidome is a complex signaling pathway consisting of several G protein-coupled receptors, metabolic enzymes and more than 20 lipid mediators. Recent research links this pathway to intestinal health. With the discovery of endocannabinoid receptors in the gut, mechanisms underlying crosstalk between such receptors and the gut microbiota are being investigated. Scientists have speculated that a dysregulated endocannabinoid system may lead to inflammatory bowel disease and colon cancer.

Gut-bacteria-800x600.jpg
The University of Chicago / NIH Flickr
Commensal bacteria (red) reside among the mucus (green) and epithelial cells (blue) of a mouse small intestine.

To take a deep dive into the interactions of the endocannabinoid pathway with the gut microbiome, Claudia Manca and researchers from Canada, Belgium and Italy investigated alterations in the endocannabinoidome in germ-free and conventionally housed mice, both juveniles and adults. Using transcriptomic analysis, they found that expression of several endocannabinoid receptors was reduced in the germ-free mice compared to conventionally housed ones. However, when fecal matter containing natural bacteria from healthy mice was transferred to the germ-free mice, this receptor expression was restored significantly.

Endocannabinoidome signalling tone can also be affected by the basal endocannabinoidome lipid mediator levels as well as receptor expression, so the authors used liquid chromatography-mass spectrometry lipidomics to analyze the different endocannabinoidome lipid mediators and found that their levels were altered substantially in the intestines of both kinds of mice. The levels of some of these molecules were significantly different under germ-free conditions and sensitive to the introduction of fecal matter from conventionally raised mice. Thus, germ-free and conventionally housed mice had differing global gene expression of endocannabinoidome.

The research shows that lack of gut microbiota significantly altered the levels of endocannabinoid receptors as well their effector molecules at the transcriptome level in the small and large intestines of mice. Published in the Journal of Lipid Research, this study provides evidence of direct interaction of the endocannabinoidome with gut microbiota and opens new avenues to investigate the pathophysiological role of endocannabinoid signaling.

A novel method to detect brain DHA turnover

Docosahexaenoic acid, or DHA, is essential for brain development in infants and normal functioning of adult brain. The brain can produce only a limited quantity of this polyunsaturated fatty acid, so it depends on a supply from circulating blood to replenish the metabolized DHA. Decreased DHA levels in the brain are associated with the onset of Alzheimer’s disease, making DHA metabolism in the brain an important topic of research. However, the existing method to study DHA turnover requires infusing stable isotope tracer-labeled fatty acid followed by tracing its metabolism kinetics. Not only is this approach expensive and complicated, but its limitations include inaccurate measurement of steady-state kinetics.

To circumvent these issues, R. J. Scott Lacombe and colleagues at the University of Toronto devised a tracer-free way of studying DHA turnover by measuring the ratio of natural 13C to 12C of DHA with high-precision gas chromatography combustion isotope ratio mass spectrometry. They fed mice with either alpha-linolenic acid or DHA for six weeks and then switched the fatty acids in their diets, followed by analyzing 13C to 12C DHA for another six months. Their results, published in the Journal of Lipid Research, correlate to findings using isotope tracers.

Treating insulin resistance: To err on the side of caution

In the pathological condition known as insulin resistance, cells fail to respond to insulin, resulting in increased blood glucose levels. This can result in increased risk of Type 2 diabetes, heart attacks, strokes and cancer. An underlying cause of this condition is an excess of circulating fatty acids, which promotes the oxidation of fat over glucose. Thus, inhibition of fatty acid oxidation, or FAOX, has been suggested as a treatment for insulin resistance.

Anne-Marie Lundsgaard and a team from Germany and Denmark performed a collaborative study to understand the consequences of inhibiting FAOX on overall metabolism. They used etomoxir to inhibit FAOX in mice, which in the short term resulted in increased glucose oxidation and lowered blood glucose as expected. However, within days, the treatment also resulted in triglyceride accumulation in the heart and liver. In fact, when etomoxir was administered to mice over a prolonged period, it resulted in hepatic steatosis or fatty liver disease and glucose intolerance. Their findings, published in the Journal of Lipid Research, shed light on the long-term consequences of FAOX inhibition for treating insulin resistance, which could move researchers to rethink such treatment strategies.

Isha Dey

Isha Dey is a scientist at Thermo Fisher Scientific in India.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

'Every experiment and every breakthrough matters'
Health Observance

'Every experiment and every breakthrough matters'

February 26, 2021

An interview with NYMC dean Marina K. Holz, who studies a rare disease that affects women of childbearing age.

Progeria: From the unknown to the first FDA-approved treatment
Health Observance

Progeria: From the unknown to the first FDA-approved treatment

February 25, 2021

Hutchinson–Gilford progeria syndrome is a rare, fatal genetic disease that causes premature aging.

Raising awareness and funding for Pompe disease
Health Observance

Raising awareness and funding for Pompe disease

February 25, 2021

Father-turned-advocate has founded multiple organizations to support families and search for better therapies for people with rare lysosomal storage disorder.

A novel approach to septic shock leads to a prospective new therapy
Journal News

A novel approach to septic shock leads to a prospective new therapy

February 23, 2021

A French research team finds new evidence supporting endotoxin removal for treating life-threatening inflammation.

When scientists become allergic to their research
News

When scientists become allergic to their research

February 21, 2021

Researchers spend long periods of time around the organisms they study. Sometimes, that exposure has unintended effects.

In mice, a mother's love comes from the gut
News

In mice, a mother's love comes from the gut

February 20, 2021

Scientists from the Salk Institute report a new influence on maternal behavior arising from an unexpected source.