Excessive-fat diets drive the manufacturing of inflammatory immune cells within the bone marrow of mice

Scientists have proven that high-fat diets could cause fast modifications within the bone marrow of mice, driving the manufacturing of inflammatory immune cells, in line with findings revealed as we speak in eLife.

The outcomes could assist clarify how high-fat diets set off irritation, which might contribute to the event of insulin resistance, sort 2 diabetes and different problems in people with weight problems.

An invasion of inflammatory immune cells, known as monocytes, into fats tissue is a trademark of weight problems, however what results in this dangerous phenomenon is unclear. Many immune cells, together with monocytes, are produced within the bone marrow, which could be very delicate to environmental modifications. Scientists have already proven that fats cells within the bone marrow quickly increase in response to a high-fat food regimen.

We needed to know if bone marrow tissue was an early responder to a high-fat food regimen that might function a precursor to the irritation noticed in weight problems. Do high-fat diet-induced modifications within the bone marrow result in the manufacturing of the inflammatory monocytes that invade fats tissue in folks with weight problems?”

Amira Klip, Senior Creator, Senior Scientist in Cell Biology at SickKids, and Professor within the Departments of Paediatrics, Biochemistry, and Physiology on the College of Toronto, Canada

Klip and colleagues discovered that mice fed a high-fat food regimen start to expertise metabolic disturbances all through their physique and within the bone marrow inside three weeks. Fats cells within the bone marrow multiply and tackle white fats cell traits. Metabolic modifications within the monocytes on the bone marrow cells additionally happen – they use much less oxygen to interrupt down sugar into power, and lactic acid builds up within the cells and surrounding fluid. The workforce additionally discovered that mitochondria, mobile factories that break down sugar into power, break aside into fragments throughout the monocytes and grow to be much less environment friendly. This strategy of mitochondrial fragmentation is related to insulin resistance.

Over a number of weeks, the variety of monocytes within the bone marrow shifts to incorporate much less of a monocyte known as Ly6Clow to extra of a monocyte known as Ly6Cexcessive, the identical sort of monocyte that invades fats tissue in folks with weight problems. This accumulation of Ly6Cexcessive monocytes within the bone marrow begins earlier than monocytes construct up in fats tissue in the remainder of the physique to grow to be inflammatory macrophages – the mature type of monocytes.

“These outcomes present that high-fat diets could cause remodelling in bone marrow fats cells that disrupt the traditional steadiness of monocytes, and might subsequently result in invasive Ly6Cexcessive monocytes spilling into the physique”, continues Klip.

The workforce additional demonstrated that white fats tissue can spur these modifications in experiments utilizing cell samples from mice fed a high-fat food regimen. Additionally they discovered that brown fats tissue, which is extra plentiful in leaner folks, could cause a shift in the direction of the non-invasive Ly6Clow monocytes.

“Our research reveals how high-fat diets set off a cascade of irritation within the physique that entails the bone marrow,” concludes Klip. “Extra analysis is required to grasp this course of additional and discover out if there are methods to stop or reverse this course of. It can even be essential to know if the bone marrow can be an early responder to weight problems in people. Studying extra may result in new therapies for treating weight problems and stopping problems resembling diabetes.”

Journal reference:

Boroumand, P., et al. (2022) Bone marrow adipocytes drive the event of tissue invasive Ly6Cexcessive monocytes throughout weight problems. eLife. doi.org/10.7554/eLife.65553.

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