Abstract 722: Relationships Among Thermogenic, Fibrotic, and White Adipose Tissue Cells in the Perivascular Niche

The perivascular adipose tissue (PVAT) forms a distinct outer layer of the vasculature and actively participates in blood pressure regulation and cardiovascular disease. In obese individuals, PVAT dysfunction has been associated with vascular hypertrophy and immune cell infiltration, which participates in atherosclerosis progression and arterial stiffness. Thoracic PVAT (tPVAT) expresses brown adipocyte-related genes and has been suggested to be protective against vascular disease progression. However, tPVAT adipocyte phenotype and signaling pathways responsible for the phenotypic changes during physiological and pathophysiological conditions including obesity are unknown. Our data demonstrate that mature adipocytes from tPVAT are a distinct adipocyte population from classical brown and white adipocytes. Perturbation of housing temperature lead to a rapid tPVAT remodeling. Using adipocytes and progenitor’s lineage tracing in adult mice, we determined that tPVAT adipocytes arise from both Prx1 and SM22 positive cells upon β-3-adrenergic stimulation while housing at thermoneutrality blocked the recruitment of new cells, resulting in a whitening of the depot. High fat diet or high fat high sucrose diet feeding both led to excessive tPVAT whitening, and this phenotype was even more pronounced under thermoneutral conditions. The whitening process was associated with a thicker medial layer and vascular fibrosis. It involves mature adipocytes loss of thermogenic markers and an increased expression of extracellular matrix genes. Interestingly, β-3-adrenergic stimulation rescued this phenotype by inducing new adipocytes recruitment and tissue remodeling. Overall, we demonstrate that tPVAT adipocytes whitening under obesogenic conditions contribute to vascular fibrosis thereby participating in arterial stiffness. Moreover, adrenergic stimulation lead to a reduced fibrosis by promoting thermogenic adipocyte recruitment. Inducing tPVAT remodeling by targeting mature adipocytes and/or promoting new thermogenic adipocyte formation may constitute a novel approach for preventing cardio-metabolic complications.