Research Spotlight: AdipoAtlas: A reference lipidome for human white adipose tissue

Posted on February 03, 2022

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Since 1975, worldwide obesity has nearly tripled. As of 2016, almost 2 billion adults are overweight, and about one-third of those are obese. Even children under the age of five are becoming obese at an alarming rate. Nearly 40 million children under the age of 5 were determined to be obese in 2020. At least 2.8 million people die every year as a result of being overweight or obese. It is easy to see that a better understanding of the disease’s etiology and discovering diagnostic and prognostic markers of the disease is important on a global scale.

How can we discover biomarkers for obesity?

Obesity is characterized by the expansion and dysregulation of white adipose tissue (WAT). The remodeling of the lipidome in WAT in patients with obesity can give us a better understanding of the disease and possibly provide biomarkers for the disease. To make this possible, our February Lipid Leader, Dr. Maria Fedorova, and her team at TU-Dresden wanted to provide a detailed quantitative description of depot-specific WAT lipidomes in lean and obese humans. Thus, they developed AdipoAtlas: a mass-spectrometry-based reference lipidome of human WAT reporting over 1600 and 700 lipid species on qualitative and quantitative levels, respectively. Let’s take a look at what they found!

Deep-Profiling the WAT lipidome.

To provide non-discriminative qualitative and quantitative inventory of the human WAT lipidome, the workflow included three main steps: 1) tissue-tailored lipid extraction and fractionation, 2) identification of lipid molecular species by using multiple separation and MS analysis platforms, 3) semi-absolute quantification of human WAT based on lipid-class-specific internal standards that were carefully selected. This workflow led to some interesting discoveries.

Triglycerides (TG) are known to accumulate in the WAT of obese humans. Interestingly, over 70% of the TGs in human WAT were composed of only 20 TG species. Most of these were saturated TGs but PUFA-rich TG species were most abundant in obese WAT. Another important discovery of AdipoAtlas was the diversity of WAT sphingolipidomes. Recent interest in sphingolipids as biomarkers of diseases produced studies showing that elevated ceramide levels were present in WAT in obesity and obesity-associated diseases. AdipoAtlas identified two atypical ceramide (Cer) classes in human WAT that were highly abundant: deoxyCer and sphingadienineCer. DeoxyCer levels in plasma have been linked to age, BMI, and waist-to-hip ratio. In plasma, they typically have a concentration of 0.1-0.3%, but in WAT the concentration was found to be 10-times higher. This shows that WAT is a reservoir of the potentially toxic deoxyCer species. Another important find from AdipoAtlas was the abundance of ether phospholipids (ePLs). ePC and ePE made up over 40% of the total PC and PE lipid composition in WAT. Furthermore, PUFA-rich ePE was the fourth most abundant lipid species in the human WAT.

AdipoAtlas and the research done by Dr. Fedorova and her team provided a deep lipidomic profile of human WAT lipidome. Inventory of over 1600 molecular species and 23 lipid subclasses were provided in the study. As mentioned, this study discovered several new lipid signatures characteristic of obesity, as well as reproducing several other signatures that were previously discovered. This study took advantage of several Avanti Lipidomic products including Cer/Sph Mixture 1, SPLASH LIPIDOMIX, and several individual lipid species. Thank you Dr. Fedorova for being a valued customer and for participating in our Lipid Leader Interview Series.

Please take the time to read the full research article published in Cell Reports Medicine. And if you are interested in hearing about more research from Dr. Fedorova, please register for Avanti’s Explore the Lipidome Webinar Series featuring Dr. Fedorova and other exciting speakers!