In the recent years, CIT has gained considerable interest and has been proposed as a potential treatment for metabolic disorders, as it leads to an increase in energy expenditure, oxidation of glucose and triglycerides as substrates, and insulin sensitivity enhancement [50, 60, 61]; Although lifestyle programs involving exercise or diet are effective for metabolic disorders, long-term adherence is often not realized, justifying the need for other approaches, such as environmental adjustment (i.e., cold exposure) [8]. The gene discussed is INS; the disease is metabolic disease.