Lipid Species Offer Insights into Metabolic Health

Heart disease is the number one killer in the USA, and high triglyceride levels in the blood are cited as just one of several risk factors. Millions of lipid panels, blood tests that look at cholesterol levels as well as triglycerides, are performed in clinics each year.

Aberrant levels of storage lipids (triacylglycerol [TAG]), circulating lipid-protein complexes (lipoprotein particles), and membrane lipids (phospholipids [PL] and diacylglycerols [DAG]) have been linked to metabolic dysfunction, such as seen in the metabolic syndrome, whose features include obesity, insulin resistance, cardiovascular diseases, and non-alcoholic liver disease (NAFLD).

Scientists at the Morgridge Institute for Research (Madison, WI, USA) and their international colleagues enrolled 29 males and 15 females and used a murine model in a study of individual species of triglycerides. Fasting whole blood samples were obtained by venipuncture after an overnight fast of eight hours or more and processed for plasma within two hours on the day of liver biopsy. Routine blood tests were performed at a university hospital and included measures of alanine transaminase (ALT), aspartate transaminase (AST), fasting TAG, cholesterol, glucose and insulin.

The biochemical tests were performed according to the manufacturer instructions for each parameter. Liquid chromatography–mass spectrometry (LC-MS) analysis was performed on an Ascentis Express C18 column using an Accela LC Pump (400 μL/min flow rate.

The team found quantitative trait loci (QTLs) for ∼94% of the lipids measured. Several QTLs harbored genes associated with blood lipid levels and abnormal lipid metabolism in human genome-wide association studies. Lipid species from different classes provided signatures of metabolic health, including seven plasma triglyceride species that associated with either healthy or fatty liver. This observation was further validated in an independent mouse model of non-alcoholic fatty liver disease (NAFLD) and in plasma from NAFLD patients. This work provides a resource to identify plausible genes regulating the measured lipid species and their association with metabolic traits.

Molly McDevitt, BS, a graduate student and co-first author of the study, said, “We don't even know how many different triglycerides there are – hundreds, thousands. We found that some triglycerides correlate positively with a fatty liver, while others correlate negatively with a fatty liver. Lumping all triglycerides into one class masks these subtler associations.” The study was published on June 13, 2018, in the journal Cell Systems.

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Morgridge Institute for Research