Establishing a Role for Sarcospan as an Obesity‐Susceptibility Gene in Mice

Abstract

This study verifies genome-wide association studies that connect variants in the SSPN locus, encoding the protein sarcospan, with increased waist circumference and heightened susceptibility to cardiovascular disease. We hypothesized that deletion of SSPN would protect SSPN-null mice from diet-induced obesity. To test this SSPN-null and WT (C57BL/6J) male and female mice were subjected to high fat diet (HFD) (60%) and compared to equivalent controls. After 16 weeks HFD, mice were assessed for changes in anthropometric indices, histology, glucose handling, blood chemistry, cardiac function and tissues for ectopic lipid deposition. Our in vivo findings suggest that SSPN plays a role in adiposity and specific variants in the gene locus may increase/decrease susceptibility to central adiposity thereby heightening risk of cardiometabolic disease. SSPN-null male mice were partially protected from weight gain, liver steatosis and had slightly improved glucose handling compared to WT males after HFD. After HFD, female SSPN-null mice had only a small increase in body weight compared to WT females. EchoMRI was used to measure % Fat per body weight. WT female mice had significantly higher % Fat after HFD compared to WT controls, while % Fat in female SSPN-null mice was largely similar after the HFD regimen. Blood chemistry measurements suggested liver damage in HFD WT mice since alanine aminotransferase (ALT) levels (U/L) were significantly elevated with levels higher in males than females. SSPN-null mice of both genders and diets however exhibited similar ALT levels. Cardiac function remained largely preserved in all groups of mice after HFD, therefore extended studies may be needed. In conclusion, deletion of the SSPN gene protects both females and males from diet-induced obesity and future studies will ascertain how it affects cardiovascular health.