(P04-009-25) Effect of Caloric Restriction on Organ Size and Its Contribution to Metabolic Adaptation: An Ancillary Analysis of CALERIE 2

Objectives: Caloric restriction (CR) improves human health, though underlying mechanisms related to energy metabolism remain unclear. This ancillary investigation of CALERIE – the only randomized controlled trial of long-term CR in normal-weight adults – aimed to quantify metabolic adaptation following 1 and 2 years of CR by assessing changes in energy-expending tissues and organs using magnetic resonance imaging (MRI).

Methods: Participants in the CR group were prescribed 25% CR for 2 years, whereas the control group were asked to maintain ad libitum food intake. At baseline, 1 and 2 years, sleeping energy expenditure (SleepEE) was assessed in a whole room indirect calorimeter and body composition was assessed using both dual energy X-ray absorptiometry (DXA) and MRI. Predicted values for SleepEE were generated from linear regression equations developed at baseline using body mass or body composition derived from DXA or MRI. Metabolic adaptation at 1 and 2 years was calculated as the difference between measured and predicted SleepEE changes.

Results: The CR group experienced reductions in adipose tissue and skeletal muscle mass compared to the control group. Sleeping energy expenditure decreased more than predicted at 1 year, regardless of whether predictions were based on body mass (-45 kcal/d; 95% CI: -87, -2; P=0.04), DXA-derived fat and fat-free mass (-79 kcal/d; 95% CI: -122, -37; P< 0.001), or MRI-derived tissue and organ mass (-91 kcal/d; 95% CI: -134, -48; P< 0.001). MRI-derived models explained ~5% more variability in energy expenditure at baseline and detected larger metabolic adaptation than simpler models based on body mass only. At 2 years, only the models based on DXA (-57 kcal/d; 95% CI: -100, -15; P=0.008) and MRI (-76 kcal/d; 95% CI: -119, -33; P< 0.001) were indicative of persistent metabolic adaptation.

Conclusions: The findings indicate that metabolic responses to CR tend to be higher when they are measured using methods that consider body composition compared to only body mass. Further, advanced imaging techniques hold potential to provide insight into organ-specific contributions to energy metabolism during CR.

Funding Sources: National Institutes of Health, Pennington/Louisiana Nutrition and Obesity Resource Center, Louisiana Clinical and Translational Science Center.