Myosteatosis and Mast Cell Accumulation in Skeletal Muscle Adjacent to Bones in Lepr-Mutant Mice Model of Obesity and Type II Diabetes

Obesity is a public health issue associated with many inflammatory processes that can alter the bone marrow, which depends on a microenvironment regulated by stromal cells (adipocytes) and cytokines. Bone marrow adipocytes play an essential role in hematopoietic stem cells (HSCs) signaling and differentiation and in the bone marrow’s niche modulation. The visceral adipose tissue systematically signals and causes alterations in the marrow’s microenvironment and adjacent tissues. Furthermore, the stroma-vascular fraction (SVF) from white adipose tissue (WAT) includes immune hematopoietic cells, among which, mast cells and their progenitors that contribute to diet-induced obesity. However, a causal relation and all the factors involved in adipose-derived hematopoietic alterations haven’t been completely described yet. Therefore, aiming to describe the hematopoietic alterations in mice affected by obesity and type II diabetes, BKS/db mice (Lepr receptor mutated) at ages 12 to 22 weeks (4-5 animals) were evaluated concerning weight and glycemia and analyzed by histopathological methods. Bones and muscle adjacent to bones were fixed in formalin, FFPE processed, and stained using hematoxylin and eosin and Giemsa. The results showed that males and females with obesity expressed progressive weight growth, with males showing higher glycemic measures than females. Beyond that, Giemsa staining revealed mast cells in the bone marrow and associated with adipocyte infiltrations near skeletal muscle in mice at 12, 14, 16, and 22 weeks. Mast cells were already associated with white and visceral adipose tissue, however, data showing their association with adipocyte stromal bone marrow cells and muscle adipocytes were scarce. That way, we concluded that obesity and diabetes indirectly lead to alterations in the muscle tissue associated with the bone, such as adipocyte infiltration and the presence of mast cells, which deserve to be deeply investigated.