Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C098

Oral Communications

Age, perivascular adipose tissue and browning: the effect of chemically induced browning differs from endogenous browning in aged mice.

M. Marchetti1, M. Friederich-Persson1

1. Department of Medical Cell Biology, Biomedical Center,, University of Uppsala, Uppsala, Sweden.

Perivascular adipose tissue (PVAT) regulates vascular tone through release of anti-contractile factors and studies report dysfunctional PVAT in conditions of cardiovascular disease. In pathologies such as hypertension, where dysfunctional PVAT is present, browning i.e. the shift from white to brown adipocyte phenotype may be a protective mechanism to prevent cardiovascular disease. The prevalence of cardiovascular disease is increasing with age and we therefore aimed to study the role of browning of PVAT in aging. Browning was induced by β3 agonist in aged male C57bl/6 mice (32-34 weeks old) through stimulation with β3 agonist (CL-316.243 1 mg/kg/day n=4) or saline (n=4) for one week. We interrogated our model through histology and wire myography to evaluate levels of browning, inflammation and vascular function, comparing aged animals with young (12-14 weeks old). Histological analysis confirmed increased uncoupling protein-1 (UCP-1, marker of browning) in β3 agonist treated animals. Saline treated old animals displayed increased levels of UCP-1 compared to young animals. Old animals treated with β3 agonist displayed further increased levels of UCP-1 (Figure 1A). Periodic Acid-Schiff Reagent Staining (PAS) showed increased expression of positive areas in the aged animals exposed to browning compared to young animals exposed to browning and compared to old saline controls (Figure 1B). Wire myography was employed to evaluate the contractile function, endothelium-dependent and independent relaxation in the presence and absence of PVAT and the data is currently under analysis. Taken together, our data suggest that aging in male C57bl/6 mice increases the endogenous level of browning as well as the susceptibility to browning from β3 adrenergic agonist. However, this chemically induced browning in aged animals is also associated with increased presence of glycogen and glycoproteins typically associated with inflammation and fibrosis. These data imply that while endogenous browning is enhanced by aging, chemically induced browning in the context of aging may be detrimental. Further analysis of data from wire myography will clarify the impact of the observed results on vascular function.

Where applicable, experiments conform with Society ethical requirements