LEP and Insulin resistance: Although leptin is capable of controlling appetite and weight gain in humans and rodents, through the central circuits in the hypothalamus and suppressing food intake as well as speeding up energy expenditure, in case of overfeeding or an increase in calorie ingestion, the increased flux of glucose in the muscle and adipose tissues triggered peripheral insulin resistance and increase of leptin biosynthesis, but it is failed to reduce feeding behavior and prevent weight gain due to leptin resistance [52,53]