Metabolic Consequences of Skeletal Muscle Specific High Expression (SM-HE) of mu-Crystallin Following Low-and High-Fat Diet Interventions are Diet and Sex-Specific

mu-Crystallin is a thyroid hormone binding protein but its role in metabolism is poorly understood. Our previous work on mice with skeletal muscle- specific high expression (SM-HE) of mu-crystallin ( Crym-tg), showed a shift towards oxidative metabolism away from glycolysis (13.7%, as measured by RER via indirect calorimetry), as well as increased expression of slow twitch muscle fiber genes as identified via RNA-seq.Here we report the effects of challenging both male and female, Crym-tg and wildtype littermates to low- and high-fat diets (LFD or HFD). Mice were placed on either diet for 16 weeks, and then subjected to QMR for body composition analysis as well as glucose and insulin tolerance tests (GTT and ITT). Mice were then acclimated to CLAMS cages and studied by indirect calorimetry during ad libitum and fast/refeed conditions. Voluntary wheels were then introduced, and indirect calorimetry measures were again collected, GTT and ITT testing was repeated before harvesting tissue for mRNA and protein interrogation.Our results show sex- and diet-specific differences between Crym-tg and WT littermates. Male Crym-tg mice on LFD weigh significantly less than their WT counterparts due to differences in lean mass. Female mice on LFD show no change in overall mass or body composition compared to controls. Female Crym-tg mice on HFD weigh significantly less than WT, again due to changes in lean mass. Males on HFD did not show significant changes in overall mass or body composition. We found no distinct patterns in the parameters monitored by indirect calorimetry that could account for these changes.Following design of a qPCR array for metabolic genes of interest (GOI) (chosen from the RNA-seq data of our previous work in male Crym­-tg mice on normal chow) we saw a distinct difference in expression profiles. Selected GOI showed little variation in mice on LFD. However, dramatically significant differences were seen in mice on HFD. GOIs, when assayed for the male mice, showed a significant decrease in expression across the group for Crym-tg mice as compared to wildtype. Concomitantly, female Crym-tg mice when assayed for the same GOIs showed a significant increase in expression across the group.The work presented here highlights the need for continued studies interrogating sex-specific differences in metabolism. Our results suggest that obesity is not strictly defined by diet and exercise, but also depends on genetic factors, including the levels of expression of Crym. MMPC subcontract from the University of Georgia (R. McInroe, P.I.) 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.