Study Finds Different Types of Human White Fat Cells

The risks associated with white adipose tissue, or white body fat, depend to some extent on where that fat is.

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

Now, however — according to a new 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 at least two distinct classes of subcutaneous white fat cells.

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 differences could lead to development of novel therapies for diabetes, obesity, and related conditions.”

The paper now appears in the journal Nature Communications.

Tip of the iceberg

Although previous research had identified multiple types of white fat cells in mice, this is one of the first to have done so in humans.

Although the study identified two different types of white fat cells, that may just be the beginning. “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.

For 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 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

In addition, at maturity, the two cell subtypes exhibited very different patterns of gene expression.

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

“Body fat is linked to many different conditions beyond diabetes. This research could be important for understanding the risk factors for other metabolic diseases, such as 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 can be different from each other 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.”

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