Intra-specific variation in resting metabolic rate in MF1 mice is not associated with membrane lipid desaturation in the liver

The 'membrane pacemaker' hypothesis provides a putative mechanistic linkage between variations in energy metabolism, rates of ageing and lifespan across different species. Within species we have found positive associations between longevity and metabolism, which contrast the inter-specific trends. It is of interest to know therefore how levels of lipid desaturation in membranes are linked to variation in metabolism between individuals within species. We explored this problem by extracting membrane fatty acids from the livers of mice that varied in their metabolic rate, in a strain (MF1) where we have previously demonstrated a positive association between metabolism and lifespan. We measured resting metabolic rate (RMR) in 60 mice, each measured on three occasions, and measured their body compositions using dual energy X-ray absorptiometry (DXA). We selected 28 individuals that exhibited a wide variation in their mean resting metabolic rates (RMR) and extracted membrane lipids from the livers of these mice post mortem and analysed them for the patterns of contribution of different fatty acids. We then sought associations between the levels of membrane desaturation and the individual variability in RMR, using the proportional contributions of each fatty acid as predictors in a stepwise regression or by re-describing the variation in fatty acyl lipids using a PCA analysis and then seeking associations between scores on the derived components and RMR. We used whole animal RMRs and also RMR with the effects of body composition (fat free mass) removed. The level of individual variation in RMR was consistent with our previous observations. There was a significant positive association (p=0.019) between the proportion of palmitic acid (16:0) in the membranes and RMR, which was strengthened (p=0.014) when we adjusted RMR for differences in fat free mass. The proportion of palmitic acid (16:0) explained 20.9% of the individual variation in residual RMR. There was no association between RMR or mass adjusted RMR and the proportional representation of any other fatty acid, including 22:6 (DHA) predicted by the membrane pacemaker hypothesis to be of particular significance. High levels of saturated fatty acids in the membranes of mice with high rates of metabolism may contribute to their greater longevity, but the mechanism tying together increased membrane saturation with elevated RMR remains unclear.