Sphingolipid LC–MS/MS: Anorexia vs. Obesity

Anorexia nervosa, an eating disorder in which people severely restrict how much they eat, and obesity sit at opposite ends of the spectrum when it comes to the body’s energy balance, and both bring major changes in how the body processes fats, sugars, and other nutrients. A growing body of research suggests that sphingolipids, a family of fats found in cell membranes, play a key role in heart and metabolic health, inflammation, and how the body responds to insulin. However, studies of these fats in patients have usually looked at anorexia and obesity separately, and no one had yet compared the two directly using the same methods.

To address this, researchers from the University of Milan and the Italian Auxological Institute set out to see whether women with anorexia or obesity have different patterns of these fats in their blood, both compared with healthy women of normal weight and compared with each other. They measured the fats in blood samples using liquid chromatography-tandem mass spectrometry (LC–MS/MS) to separate the components of a sample and then identify and measure them precisely. A paper based on their work was published in the journal Frontiers in Endocrinology.¹

How Was the Study Carried Out?

The study looked at a group of 114 women at a single point in time: 28 with anorexia, 37 with obesity, and 49 healthy women of normal weight for comparison. For each woman, the researchers gathered a wide range of information, including her medical details, body measurements, blood test results, markers of inflammation, and measures of blood pressure and circulation.¹

To compare the three groups, the team used statistical tests suited to data that do not follow a typical pattern, and they adjusted the results to reduce the chance of false findings that can happen when many comparisons are made at once. They also used several methods that look at many measurements together to find overall patterns, see how the women naturally grouped based on their blood fat profiles, and pick out which fats did the most to set the groups apart. Finally, they checked how these fats related to factors linked to heart and metabolic health, while taking each woman’s age into account.¹

What Did the Testing Reveal About Blood Fat Patterns in Women with Anorexia and Obesity?

The three groups differed in their general health and metabolic measures, and the differences in their blood fats were striking. Of the 45 sphingolipid measurements the team looked at, 38 differed meaningfully between the groups, even after adjusting for the risk of false findings. These differences showed up across many types of sphingolipids, not just one or two. Women with anorexia had higher levels of several kinds of these fats, including ones that form part of cell membranes and ones that act as signaling molecules in the body. Women with obesity showed a different pattern: they had more of certain fats that are early building blocks in sphingolipid production, along with shifts in the balance between different ceramides (a type of sphingolipid linked to metabolic health), and lower levels of some larger, more complex sphingolipids.¹ The researchers consider this to be one of the study’s most important findings, as it means the differences between women with anorexia, women with obesity, and healthy women were notjust a few lucky or random results. Instead, they reflected a consistent, reliable pattern that makes biological sense.^2-4

When the researchers looked at all the measurements together, the three groups clearly separated from one another. A statistical model built to sort the women into their groups based on their blood fats did so correctly about 85% of the time, and it pointed to a handful of specific fats as the most important for telling the groups apart. After taking age into account, many of these fats were also linked to body weight, insulin resistance, blood pressure, inflammation, and blood levels of triglycerides and “good” HDL cholesterol.¹

Overall, women with anorexia and women with obesity each have their own distinct pattern of blood fats, though the two patterns overlap in places, and the changes involve several connected processes in how the body makes and uses these fats. Anorexia was mainly linked to higher levels of membrane-related and more complex sphingolipids, while obesity was mainly linked to changes in early building-block fats and in the balance of ceramides.¹

“These findings,” write the authors of the paper,¹ “support the concept that severe undernutrition and obesity represent biologically distinct states of sphingolipid dysregulation and suggest that plasma sphingolipid signatures may serve as candidate biomarkers of metabolic remodeling and cardiometabolic risk across the extremes of energy balance.”

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References

1. Rigamonti, A. E.; Morano, C.; Dei Cas, M. et al. Sphingolipid Signatures at the Extremes of Energy Balance: A Comparative Study of Obesity and Anorexia Nervosa in Women. Front Endocrinol (Lausanne) 2026, 17, 1890712. DOI: 10.3389/fendo.2026.1890712
2. Benjamini, Y.; Hochberg, Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B Stat Methodol. 1995, 57, 289–300. DOI: 10.1111/j.2517-6161.1995.tb02031.x
3. Storey, J. D.; Tibshirani, R. Statistical Significance for Genomewide Studies. Proc Natl Acad Sci U S A 2003, 100 (16), 9440-9445. DOI: 10.1073/pnas.1530509100
4. Xia, J.; Wishart, D. S.; Met, P. A. A Web-based Metabolomics Tool for Pathway Analysis and Visualization. Bioinformatics 2010, 26 (18), 2342-2344. DOI: 10.1093/bioinformatics/btq418