Deficiency of LRP1 in Mature Adipocytes Promotes Diet-Induced Inflammation and Atherosclerosis-Brief Report.

Objective: Mice with adipocyte-specific inactivation of low-density lipoprotein receptor-related protein-1 (LRP1) are resistant to diet-induced obesity and hyperglycemia because of compensatory thermogenic response by muscle. However, the physiological function of LRP1 in mature adipocytes and its role in cardiovascular disease modulation are unknown. This study compared perivascular adipose tissues (PVAT) from wild-type () and adipocyte-specific LRP1 knockout () mice in modulation of atherosclerosis progression.

Approach And Results: Analysis of adipose tissues from and mice after Western diet feeding for 16 weeks revealed that, in comparison to mice, the adipocytes in mice were smaller, but their adipose tissues were more inflamed with increased monocyte-macrophage infiltration and inflammatory gene expression. The transplantation of PVAT from chow-fed and mice into the area surrounding the carotid arteries of mice before feeding the Western diet revealed a contributory role of PVAT toward hypercholesterolemia-induced atherosclerosis. Importantly, recipients of PVAT displayed a 3-fold increase in atherosclerosis compared with PVAT recipients. The increased atherosclerosis invoked by LRP1-deficient PVAT was associated with elevated monocyte-macrophage infiltration and inflammatory cytokine expression in the transplanted fat.

Conclusions: PVAT provide outside-in signals through the adventitia to modulate atherosclerotic lesion progression in response to hypercholesterolemia. Moreover, adipocytes with LRP1 deficiency are dysfunctional and more inflamed. This latter observation adds the adipose tissue to the list of anatomic sites where LRP1 expression is important to protect against diet-induced atherosclerosis.