Physical inactivity causes exercise resistance of fat metabolism: harbinger or culprit of disease?

Physical inactivity is the fourth leading cause of death in the world. It is associated with myriad diseases and premature death. Two possible contributing factors are postprandial lipidaemia (PPL), which accelerates atherosclerosis, and impaired whole-body fat oxidation, which contributes to obesity. Acute exercise in physically active people is effective for increasing whole body fat oxidation and lowering PPL the next morning. However, in people who have low physical activity (<8000 steps/day), an acute bout of exercise (1 h at 62% maximal oxygen consumption) has no effect on increasing fat oxidation or reducing PPL ('exercise resistance'). The acute harms of inactivity are not due to the lack of exercise and are more powerful than the benefits of exercise, at least regarding fat metabolism. The increase in mortality with reduced daily steps is remarkably steep. Low background steps/day also impair the metabolic adaptations to short-term endurance training, suggesting that the ills of inactivity extend beyond fat metabolism. 'Exercise resistance' with inactivity could be a culprit, causing atherosclerosis, or maybe also a harbinger (impaired fat oxidation) of more widespread diseases. Recommendations regarding the amount of moderate to vigorous exercise needed for health should factor in the amount of background activity (i.e. ∼8000 steps/day) necessary to avoid 'exercise resistance'.