|Mariana Kiomy Osako
Tel.: (16) 3315-3346
Investigation of RANK-RANKL signaling as bone endocrine player in different tissues targeting mitochondrial biogenesis and its impact in beige adipocyte differentiation, immunometabolism as for macrophage polarization between pro and anti-inflammatory states, and in skeletal muscle fiber differentiation.
RANKL system consists of two receptors: RANK and Osteoprotegerin (OPG), and one ligant: RANKL. This system is usually related to bone metabolism, but it is present in different tissues where it regulates immune cells communication, mammary gland development, and recently we have reported its contribution for arterial calcification and prevention of neuronal death after stroke.
OPG has been considered a biomarker for obesity, type 2 diabetes, cardiovascular diseases and ischemic stroke, however, the biological mechanism that explain OPG level increase in these different pathologies is unclear. Our goal is to investigate RANK-RANKL signaling in macrophages, adipose tissue and skeletal muscle under physiological state and insulin resistance context.
1- 1) Macrophage phenotypic polarization in adipose tissue inflammation:
Adipose tissue of obese patients presents pro-inflammatory macrophage infiltration, which impairs tissue insulin response and may culminate in type 2 diabetes. We aim to elucidate the molecular mechanism underlying TLR4 pathway and M1 macrophage inhibition elicited by RANK-RANKL activation, and to evaluate its contribution in adipose tissue inflammation in obesity-induced type 2 diabetes murine models.
2- 2) Beige adipocyte differentation and related signaling pathways:
White adipocyte differentiation to beige adipocyte in a process known as browning poses as potential target for treating obesity and related diseases as beige adipocyte show lower and smaller lipid droplets accumulation, thermogenesis ability, and increased energy expenditure as it dissipates cell fuel as heat. We investigate adipogenesis of white and beige adipocyte, and mitochondrial biogenesis pathways regulated by RANKL to clarify cross-talk between bone and adipocyte.
3-3) Skeletal muscle fiber differentiation and determination
We investigate mitochondrial biogenesis and degradation for skeletal muscle fiber determination in knockout or heterozygous for OPG to understand the molecular mechanism underpinning the cross-talk of bone and muscle; and how RANK-RANKL signaling impact on insulin response as impairment in glucose uptake in skeletal cell along with adipocyte is target for treating type 2 diabetes.