The obesity and the associated non-communicable diseases (NCDs) are globally increasing in their prevalence. While the modern-day lifestyle required less ventilation of metabolic energy through muscular activities, this lifestyle transition also provided the unlimited accession to foods around the clock, which prolong the daily eating period of foods that contained high calorie and high glycemic load. These situations promote the high continuous flux of carbon substrate availability in mitochondria and induce the indecisive bioenergetic switches. The disrupted bioenergetic milieu increases the uncoupling respiration due to the excess flow of the substrate-derived reducing equivalents and reduces ubiquinones into the respiratory chain. The diversion of the uncoupling proton gradient through adipocyte thermogenesis will then alleviate the damaging effects of free radicals to mitochondria and other organelles. The adaptive induction of white adipose tissues (WAT) to beige adipose tissues (beAT) has shown beneficial effects on glucose oxidation, ROS protection and mitochondrial function preservation through the uncoupling protein 1 (UCP1)-independent thermogenesis of beAT. However, the maladaptive stage can eventually initiate with the persistent unhealthy lifestyles. Under this metabolic gridlock, the low oxygen and pro-inflammatory environments promote the adipose breakdown with sequential metabolic dysregulation, including insulin resistance, systemic inflammation and clinical NCDs progression. It is unlikely that a single intervention can reverse all these complex interactions. A comprehensive protocol that includes dietary, nutritional and all modifiable lifestyle interventions, can be the preferable choice to decelerate, stop, or reverse the NCDs pathophysiologic processes.