Study finds various kinds of human white fat cells

Discovering that white fat cells aren't all the same can help researchers better understand the role of fat cells in disease.

The risks connected with white adipose tissue, or white surplus fat, depend somewhat on where that fat is.

For instance, intra-abdominal fat (belly fat) is more likely to bring about diabetes and other metabolic conditions than white body fat located just beneath the skin (such as for example in the hips and thighs).

Now, however - according to a fresh paper from the Joslin Diabetes Center in Boston and Boston University, both in Massachusetts - it appears that there is more to it than that: There are in least two distinct classes of subcutaneous white fat cells.

“A central question inside our research on metabolic disease is whether white fat cells in various parts of the body, and even within a single part of the body, will vary enough that some might predispose you to disease plus some may not,” says co-senior author C. Ronald Kahn, your physician and scientist.

Immature white fat cells do not follow a single, universal trajectory to maturity. They can develop different patterns of gene expression.

Kahn is hopeful that “determining the mechanisms for these dissimilarities could cause development of novel therapies for diabetes, obesity, and related conditions.”

Tip of the iceberg

Although previous research had discovered multiple types of white fat cells in mice, that is among the first to did so in humans.

The paper may be the product of a unique collaboration, says Kahn. According to senior co-author Simon Kasif, a biomedical engineer, “The study highlights the potential of bringing interdisciplinary expertise from four laboratories to integrate biology, artificial intelligence, systems biology, and data obtained from clinical samples to catalyze discovery.”

Although the study identified two different types of white fat cells, that may just be the start. “We think this research is the tip of the iceberg - if we study more samples of human fat, we will find more subtypes,” says Kahn.

Pairs of teams

Single-cell RNA sequencing allows scientists to track the genetic development of single fat cells from their precursor, or “preadipocyte,” stage to their mature patterns of gene expression.

Because of this project, the researchers used white subcutaneous fat cells from a biobank of specimens that scientists had previously collected from healthy individuals.

Scientists at the Broad Institute of MIT and Harvard in Cambridge, MA, and the Joslin laboratory of Yu-Hua Tseng then performed single-cell RNA sequencing on these samples.

Researchers performed an integrated analysis of both datasets by using a novel mathematical technique that helped reveal the cells’ patterns of gene expression. It revealed that the datasets depicted two distinct white fat cell subtypes.

Two different subtypes

To get started with, as preadipocytes, one subtype expressed much higher degrees of “zinc nuclear finger” genes. That is a couple of master regulator genes, the function which researchers usually do not yet understand. However, they could help control cells’ maturation, say the paper’s authors.

Furthermore, at maturity, both cell subtypes exhibited completely different patterns of gene expression.

The patterns in a single subtype, for instance, indicated a significantly higher intake of glucose, which is an important metabolic resource.

“Body fat is associated with many different conditions beyond diabetes. This research could possibly be important for understanding the risk factors for other metabolic diseases, such as for example fatty liver disease and atherosclerosis, and even non-metabolic diseases that are increased by obesity, such as cancer and Alzheimer’s disease.”

- C. Ronald Kahn

That white fat cells could be different from one another also fits with another growing area of research.

According to Kasif: “Metabolic diseases are highly associated with environmental factors. This work supports the relatively understudied hypothesis that environmental factors may modify the trajectory of how cells develop and our understanding of how this process may influence biology and metabolic disease.”