The effects of graded levels of calorie restriction: VIII. Impact of short term calorie and protein restriction on basal metabolic rate in the C57BL/6 mouse

Abstract

Under calorie restriction (CR) animals need to lower energy demands. Whether this involves a reduction in cellular metabolism is an issue of contention. We exposed C57BL/6 mice to graded CR for 3 months, measured BMR and dissected out 20 body compartments. From a separate age-matched group (n=57), we built 7 predictive models for BMR. Unadjusted BMR declined with severity of restriction. Comparison of measured and predicted BMR from the simple models suggested suppression occurred. The extent of suppression was greater with increased CR severity. However, when models based on individual organ sizes as predictors were used, the discrepancy between the prediction and the observed BMR disappeared. This suggested metabolic suppression was an artefact of not having a detailed enough model to predict the expected changes in metabolism. Our data have wide implications because they indicate that inferred metabolic impacts of genetic and other manipulations may reflect effects on organ morphology.

The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome

“…These observations can be reconciled if the animal under CR disproportionately reduces the amount of tissues in its body to more than compensate for the reduced energy intake, providing scope to elevate the tissue level of expenditure [ 109 , 110 ]. For the same individual mice studied in the present paper we have shown that the level of basal metabolic rate [ 21 ] is consistent with the measured changes in body composition at the end of the restriction period [ 15 ]. In fact, the increased gene expression in the glycolysis/TCA cycle/ETC was negatively correlated with the measured BMR and average body temperature (Figure 11 ).…”

“…We previously measured urinary major urinary proteins (MUPs), food anticipatory activity (FAA) and basal metabolic rate (BMR) in the same animals [ 15 , 18 , 21 ]. We assessed whether changes in urinary MUPs, FAA and BMR were associated with gene expression levels of genes involved in the insulin/IGF-1 signaling pathway.…”

“… Previously measured leptin and insulin levels, food anticipatory activity (FAA), body temperature (body T) and basal metabolic rate (BMR) [ 15 , 16 , 18 , 21 ] for each individual mouse were correlated with the normalized counts of genes involved in electron transport chain, gluconeogenesis, glycolysis and tricarboxylic acid (TCA) cycle. Purple indicates a negative correlation between genes and the measured physiological/behavior data while green indicates a positive correlation.…”

“…The custom built pathways do not have a z-score and hence we do not have a prediction of their down or upregulation calculated by IPA. Physiological data and behavior al data (methods and data described in [ 15 , 16 , 18 , 21 ]) were correlated with each gene and each individual using Pearson correlations conducted in the statistical environment R (version 3.2.5) [ 171 ].…”

Systemic PPARγ deletion in mice provokes lipoatrophy, organomegaly, severe type 2 diabetes and metabolic inflexibility

“…Indeed, this assumption is not true in Pparg Δ/Δ mice that show a disproportionately high enlargement of the liver compared to the total increase in lean mass. Moreover, liver has, together with the muscle, the highest mass-specific metabolic rate [40] and is the organ which correlates best to basal metabolic rate [41]. Thus the hypermetabolism in Pparg Δ/Δ mice is in many respects unlike other hypermetabolic clinical situations such as HIV-associated lipodystrophy [42], burn injury or cancer, which are associated with sarcopenia or cachexia, particularly in chronic situations.…”