Scientists here suggest that the chronic inflammation generated by visceral fat tissue, an important form of metabolic disarray that drives age-related disease and dysfunction, is not produced by all fat cells. Indeed, it may be primarily produced by a specific type of progenitor cell lining blood vessels in fat tissue. This is an interesting demonstration, but it remains the case that the best solution to excess visceral fat is never to obtain it in the first place. The effects of visceral fat on metabolism quite literally accelerate the progression of degenerative aging.
When a person consumes more calories than needed, the excess calories are stored in the form of triglycerides inside fat tissue, also known as white adipose tissue (WAT). Researchers know that in obese people, WAT becomes overworked, fat cells begin to die, and immune cells become activated. But the exact mechanism by which this inflammation occurs isn't fully understood. That chronic, low-level inflammation is one of the driving factors behind many of the diseases associated with obesity.
While many studies have focused on the signaling molecules produced by the fat cells or immune cells in WAT that might contribute to inflammation, this team of researchers took a different approach. They focused instead on the vessels that carry blood - as well as immune cells and inflammatory molecules - into WAT. In 2018, the team identified a new type of cell lining these blood vessels in mice - an adipose progenitor cell (APC), or precursor cell that goes on to generate mature fat cells. But unlike most APCs, the new cells, dubbed fibro-inflammatory progenitors, or FIPs, produced signals that encouraged inflammation. In the new work, the researchers looked more closely at the role of the FIPs in mediating inflammation.
Within just one day of switching young male mice to a high-fat diet, researchers discovered that the FIPs quickly increased the number of inflammatory molecules produced. After 28 days on a high-fat diet, they found a substantial increase in the proportion of FIPs compared with other APCs. To show that the increase in the number and activity of the FIPs was not just a side effect of already-inflamed fat cells, the team removed a key immune signaling gene, Tlr4, from the FIPs in some mice. After five months on a high-fat diet, the mice lacking Tlr4 had gained just as much weight, and just as much fat, as other mice on a high-fat diet. But the genetically engineered mice - with FIPs that could no longer generate the same signals - no longer had high levels of inflammation. Instead, the levels of inflammatory molecules in their WAT were closer to the levels seen in mice on low-fat diets.
Researchers went on to show that increasing levels of a related signaling molecule, ZFP423, in FIPs can also ameliorate the inflammation in mouse fat cells. The findings point toward possible avenues to pursue to lower the risk of disease in people with obesity.