High fat diets have long been associated with obesity and diseases like Type 2 diabetes, though the mechanistic reasons remain up for debate. New research now finds that the inflammatory nature of a high-fat diet can quickly alter the bone marrow of mice, encouraging the production of inflammatory immune cells.
“We wanted to know if bone marrow tissue was an early responder to a high-fat diet that could serve as a precursor to the inflammation observed in obesity,” says senior author Amira Klip, a senior scientist in cell biology at SickKids, and a professor in the Departments of Pediatrics, Biochemistry, and Physiology at the University of Toronto. “Do high-fat diet-induced changes in the bone marrow lead to the production of the inflammatory monocytes that invade fat tissue in people with obesity?”
To answer this question, the research team fed mice a high-fat diet and observed changes that followed over some weeks. Within three weeks, the mice began to display metabolic distress throughout their bone marrow and body. The fat cells within the bone marrow began to swiftly multiply and inflammatory immune cells, called monocytes, started to become less efficient at breaking down sugar into energy. Moreover, lactic acid buildup was also promoted.
As the weeks continued to pass, the number of monocytes in the bone marrow evolved to include less of a monocyte called Ly6Clow, to more of one called Ly6Chigh. This is the same type that targets fat tissue in people with obesity. The build up of these monocytes in the bone marrow acts as a precursor to fat tissue building up in the rest of the body prior to maturing into inflammatory macrophages. However, a finding that may provide optimism is that brown fat, the fat tissue more common in people without obesity, can influence monocytes to shift back to being Ly6Clow.
The team unanimously agrees that their results are useful additions to expanding research efforts regarding diet, obesity, and chronic disease.
“Our study reveals how high-fat diets trigger a cascade of inflammation in the body that involves the bone marrow,” concludes Klip. “More research is needed to understand this process further and find out if there are ways to prevent or reverse this process. It will also be important to know if the bone marrow is also an early responder to obesity in humans. Learning more could lead to new therapies for treating obesity and preventing complications such as diabetes.”
This study is published in the journal eLife.