Assessment of the Response of Young and Aged Sarcospan-Deficient Mice to Nutrient Excess

Abstract

This study follows up on human genome-wide association studies that have identified variants in the SSPN locus. This locus encodes the protein sarcospan that segregates with several anthropometric traits. One of these traits includes an increase in waist circumference. In this study, we compared the response of young and old SSPN-deficient (SSPN-/-) and WT control mice to high fat diet (HFD) (60% fat). The HFD was initiated in 2 month and 1 year old male and female for 4 months and 5 months respectively. This study showed that SSPN-deficiency provided partial protection from weight gain in young male mice when compared to age-matched WT mice and a significantly smaller increase in body weight (BW) compared to controls. Also, young female SSPN-/- mice gained 50% less BW than WT age matched mice compared to controls and visceral WAT fat pad weights were significantly lower. To examine whether these differences are lost in aging (e.g. due to hormonal decline), we subjected 12-month old WT and SSPN-/- mice to 5 months of HFD and assessed anthropometric traits, blood lipids, glucose tolerance, body composition, and alterations of cytokine/adipokine/chemokine levels in blood serum and adipose tissue. There were signs of inflammation/fibrosis in young WT male WAT. This was largely absent in SSPN-/- mice. Interestingly, a specific subset of upregulated inflammatory mediators was found in WT WAT including leptin. However, another distinct subset of adipokines/chemokines were upregulated including adiponectin in SSPN-/- WAT. Therefore, we are investigating whether SSPN affects obesity-associated inflammatory signaling in adipocytes that influences adipose tissue expansion and ectopic triglyceride accumulation in the liver. FDOH JEK 21K12 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.