Role of the adipocyte Apolipoprotein M in obesity-related diseases ; Rôle de l'apolipoprotéine M adipocytaire dans les complications de l'obésité

The adipose tissue is a large organ whose functions are to store lipids and to secrete several factors, among which are the adipokines. A majority of adipokines have an increased secretion with obesity, like leptin, whereas few adipokines, like adiponectin, are decreased. Obesity can lead to the development of a systemic and local low-grade inflammation, which may trigger the loss of insulin sensitivity. Obesity is an important risk factor of type 2 diabetes or cardiovascular diseases. The apolipoprotein M (apoM) is a recently identified adipokine whose gene expression in humans is low in an unhealthy adipose tissue. The adipose tissue APOM gene expression is low in subjects with obesity or type 2 diabetes and is positively correlated with insulin sensitivity indexes. Therefore, apoM expression profile in adipose tissue is similar to adiponectin, which is insulin-sensitizing and anti-inflammatory, but the role of apoM in obesity is not known. First, we studied the association between plasma apoM and adiponectin in humans and their link in insulin sensitivity. No association between plasma apoM and adiponectin was found, but a negative correlation between changes in plasma apoM and changes in insulin resistance index after bariatric surgery was observed. The latter was not found for adiponectin. In vitro, in the human adipocyte model hMADS, adiponectin upregulates APOM gene expression. The mRNA levels of these two adipokines are strongly correlated, even during an inflammatory state. Accordingly, apoM could be a novel marker inversely associated to insulin resistance at the systemic level. In the adipose tissue, apoM could play a preventive role in obesity-associated low-grade inflammation. Second, we investigated the role of apoM in adipose tissue inflammation: in vivo with a murine apom-/- model and a murine model whose specifically express human APOM gene in a fat pad; in vitro using conditioned media from APOM¬-overexpressing hMADS adipocytes on the human macrophages model ThP1. We found a higher inflammation ...