LEP and obesity due to melanocortin 4 receptor deficiency: Furthermore, the HSA axis activation alleviates obesity-associated insulin resistance, alleviates hyperglycemia and dyslipidemia [11,12], alters adipokine levels with higher adiponectin and lowers leptin expression in adipose tissue as well as in circulating blood [10,12], suppresses tumor progression and metastasis [10,26], and enhances immunocompetence [10,26,27], all mimicking CR [1, 5, 28, 29].