CD11d expression is dramatically increased in white adipose tissue of obese rodents

Abstract

Macrophages (MΦ) infiltrate white adipose tissue (WAT) with increasing adiposity and are primarily localized to necrotic adipocytes. Mechanisms underlying WAT MΦ recruitment, tissue migration/retention, and function in obese animals is unclear. Integrins are cell adhesion proteins critical for leukocyte extravasation, migration, and phagocytosis. CD11d encodes the α‐subunit of the integrin αDβ2 and is expressed predominantly on monocytes/MΦ; however, its role in systemic and WAT inflammation is poorly understood. We have demonstrated for the first time that CD11d expression in retroperitoneal (RP) WAT is increased dramatically (by >200 fold) in obese female Zucker rats (n=7) compared to lean controls (n=9), further confirmed in a polygenic obese SD male rat model (~70 fold). To assess whether this upregulation in WAT is the result of obesity‐induced inflammation or generalized inflammation outside the context of obesity, we measured CD11d expression in RP WAT of non‐obese mice administered lipopolysaccharide (LPS) at 0.5 mg/kg (5 day; n=5) vs. vehicle‐treated controls. CD11d expression was increased by LPS treatment, but the fold increase (~3.6 fold) was far less than observed in obesity. Our results are consistent with the hypothesis that CD11d plays a critical role in WAT MΦ migration, tissue retention, and or phagocytosis of cellular debris and lipid from necrotic adipocytes in obesity.Grant Funding SourceWestern Human Nutrition Research Center