Laminin-α4 Is Upregulated in Both Human and Murine Models of Obesity

Abstract

Obesity affects nearly one billion globally and can lead to life-threatening sequelae. Consequently, there is an urgent need for novel therapeutics. We have previously shown that laminin, alpha 4 (<i>Lama4</i>) knockout in mice leads to resistance to adipose tissue accumulation; however, the relationship between <i>LAMA4</i> and obesity in humans has not been established. In this study we measured laminin-α chain and collagen mRNA expression in the subcutaneous white adipose tissue (sWAT) of mice placed on chow (RCD) or 45% high fat diet (HFD) for 8 weeks, and also in HFD mice then placed on a "weight loss" regimen (8 weeks HFD followed by 6 weeks RCD). To assess extracellular matrix (ECM) components in humans with obesity, laminin subunit alpha mRNA and protein expression was measured in sWAT biopsies of female control subjects (BMI<30) or subjects with obesity undergoing bariatric surgery at the University of Chicago Medical Center (BMI>35) both before and three months after surgery. Lama4 was significantly higher in sWAT of HFD compared to RCD mice at both the RNA and protein level (p<0.001, p<0.05 respectively). sWAT from human subjects with obesity also showed significantly higher <i>LAMA4</i> mRNA (p<0.01) and LAMA4 protein expression (p<0.05) than controls. Interestingly, even though LAMA4 expression was increased in both humans and murine models of obesity, no significant difference in <i>Lama4</i> or LAMA4 expression was detected following short-term weight loss in either mouse or human samples, respectively. From these results we propose a significant association between obesity and elevated LAMA4 expression in humans, as well as in mouse models of obesity. Further studies should clarify the mechanisms underlying this association to target <i>LAMA4</i> effectively as a potential therapy for obesity.