A tiny population of immune cells in the small intestine may trigger diet-induced weight gain

Confusingly, a distinct population of immune cells in the small intestine could be helping to stimulate diet-induced obesity, while the same cells in white fats have previously been shown to help burn energy.

What does this mean? It may mean that, after much more research, specifically targeting these particular immune cells could prevent weight gain and obesity, even for those eating a lot of fat.

“We were very surprised to find that the same kinds of cells appear to exert completely different functions in different tissues,” says Takaharu Sasaki, who, along with Shigeo Koyasu and Kazuyo Moro, led the study at the RIKEN Center for Integrative Medical Sciences.

The team drew their conclusions after a series of mouse experiments on a recently identified lymphocyte known as the innate lymphoid cell (ILC). The experiments showed that a particular subset of ILCs, known as small-intestine group-2 innate lymphoid cells (SI-ILC2s), may trigger the development of obesity, while a similar group of ILC2s located in white fat do not.

For the study, the group put two types of genetically engineered mice on a high-fat diet or on a regular diet. After 8 weeks, mice that lacked all lymphocytes and were fed a high-fat diet were not obese and had put on about as much weight as the same type of mice on a normal diet. In contrast, genetically engineered mice with no acquired immune cells, but with ILCs, had put on significantly more weight.

Further testing showed that in addition to gaining weight, these mice also displayed other hallmarks of obesity, such as greater amounts of white fat tissue, larger livers and impaired insulin resistance.

To probe further, the team used bone marrow cell transplants to introduce ILCs into non-obese mice that lacked all lymphocytes, and found that when fed on the 8-week high-fat diet, these mice were not resistant to weight gain or other symptoms of obesity.

The next stage of testing focused on location subsets of ILCs. The team looked at the effects of transferring small-intestine-derived ILC2s and white-fat-derived ILC2s into mice lacking all ILCs. They found that only the mice with ILC2s from the small intestine showed signs of obesity after being fed a high-fat diet. The researchers concluded that ILC2s specifically from the small intestine appear to be linked to the development of diet-induced obesity.

Sasaki hypothesizes that “an imbalance between the function of small-intestine ILC2 and white-fat ILC2 may be one of the accelerators for obesity.”

The researchers also noted that despite being fed on a high-fat diet, mice lacking ILCs were found to have lower levels of inflammation promoting M1 macrophages in their white fat tissue, which is linked to insulin resistance. They suggest these may prove to be key factors in ILC2’s role in diet-induced weight gain.