In aging mice undergoing caloric restriction, a high-fat diet during refeeding increases the respiratory exchange ratio to 0.81 ± 0.03, indicating elevated fat oxidation, but does not prevent excessive fat accumulation, demonstrating that fat oxidation alone is insufficient to limit adiposity.

When aging mice eat a high-fat diet after dieting, their brain rewards them for eating more, so they consume far more calories than needed. Even though their bodies burn more fat for energy, the excess calories are still stored as fat because the amount eaten is too high. The fat cells grow larger and release more of a hormone called leptin, but this hormone no longer tells the brain to stop eating, so overeating continues and fat keeps accumulating.