The presence of ectopic adipocytes in the muscle is known to be detrimental to the metabolism. Until now it has been accepted that these fat cells came from the maturation of a local population of fat progenitors. This study published in Cell Reports shows that in mice in a context of caloric overload, subcutaneous adipose tissue abnormally releases adipose progenitors migrating to muscle, which participate in the formation of ectopic adipocytes and associated metabolic damage.
Adipose tissue has a remarkable plasticity that allows it to adapt to large variations in energy storage. This capacity, based on the increase in the size and number of adipocytes, is however limited and in a prolonged situation of energy imbalance it is frequent to observe an accumulation of lipids called “ectopic” because not associated with adipose tissue. This is particularly the case in skeletal muscle where, in addition to the appearance of small lipid droplets within the muscle fibres, real fat cells form between the muscle fibres and are associated with metabolic disorders such as insulin resistance.
Since researchers had previously shown that subcutaneous adipose tissue in mice was able to release adipose progenitors into the circulation, they hypothesized that ectopic muscle adipocytes could come from these mobilized precursors. To test this hypothesis, they deliberately induced the repeated release of adipose progenitors in mice by pharmacologically targeting with AMD3100 the system responsible for anchoring these cells in adipose tissue (i. e. cytokine CXCL12 and its receptor CXCR4). They then observed that the released fat progenitors had infiltrated the muscle to form ectopic fat cells that altered glucose metabolism in the same way as a diet enriched in fat. Therefore, even in the absence of caloric overload, the induced release of adipocyte precursors is sufficient to mimic the formation of ectopic adipocytes observed during the fat diet and the associated metabolic degradation.
The researchers then tried to modulate this event by limiting the release of these progenitors, with the objective of reducing the harmful formation of ectopic fat cells in the muscle. Mice fed a fat diet and given intermittent treatment with Pioglitazone, an anti-diabetic agent that also has effects on the CXCL12/CXCR4 axis, showed a significant decrease in the amount of ectopic adipocytes. The effects of the molecule on the one hand increase the retention of fat progenitors within the fat tissue itself and on the other hand decrease the migratory capacities of these cells.
In the context of metabolic disorders associated with obesity, this study could help to understand the regulation of the migration of adipose progenitors to skeletal muscle and open new therapeutic strategies. On the other hand, it makes it possible to consider the quantification of circulating adipose progenitors as a diagnostic and/or prognostic biomarker of the development of metabolic diseases.