Long-term study uncovers previously unknown mechanism of the formation of fat tissue in humans.


While all red and white blood cells derive from stem cells in the bone marrow, the scientific community has been divided as to whether bone marrow cells are also able to produce other cell types. In the present study, the researches from Karolinska Institutet wanted to ascertain whether cells from the bone marrow could develop into fat cells; the problem is, however, that no experimental method is available for determining the origins of these cells in humans.

Previous studies show that adipose tissue or body fat is loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells.  Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and the cytokine TNFα. Moreover, adipose tissue can affect other organ systems of the body and may lead to disease.

In 2007, researchers isolated the adipose gene, which those researchers hypothesize serves to keep animals lean during times of plenty. In that study, increased adipose gene activity was associated with slimmer animals.  Although its discoverers dubbed this gene the adipose gene, it is not a gene responsible for creating adipose tissue.  Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes. Recent studies shed light into potential molecular mechanisms in the fate determination of pre-adipocytes although the exact lineage of adipocyte is still unclear until now.

The current study used the fact that it is possible to differentiate between grafted and native cells, the researchers conducted their study on 65 adult patients who had transplants up to 31 years ago.  The team state that this is an unprecedented follow-up period and one that can therefore give a great deal more information than the relatively short studies previously done on mice.  The opensource study is published in the journal Cell Metabolism.

The results show that during a lifetime some 10 per cent of the graft recipients’ subcutaneous fat consisted of donor-derived cells. And while this was independent of sex and age, the researchers state that the patients’ BMI was an important factor in that overweight patients had up to 2.5 times more bone-marrow-derived fat cells than slim patients. The data findings suggest that it is possible for bone marrow cells to develop into different cell types and that certain characteristics of the recipient, such as obesity, can influence this process.

The team surmise that the next step is to find out exactly which bone marrow stem cells can become fat cells.  They go on to add that these studies were done on people who had received a bone marrow transplant to treat leukaemia, and it remains to be seen if the results also apply to people who haven’t had a transplant. The researchers conclude that if they do, it could lead to new therapies for patients with metabolic diseases, in which adipose cells play a key part.

Source:  Karolinska Institutet

 

Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells may contribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute ∼10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects.  Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis.  Arner et al 2015.

Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells may contribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute ∼10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects. Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis. Arner et al 2015.

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