CLOCK and metabolic syndrome: Chronic PVN CRH activity not only activates the HPA axis to drive hypercortisolemia, itself a potent stimulus for insulin resistance and fattening [155,162,163,164,165,166], but such activity also alters the normal circadian rhythm of corticosteroid hormone critical in regulating CNS clock control of whole-body physiology as discussed above in Section 2 [167,168], and both perturbations can drive metabolic syndrome [27,155].