Fig. 6.

The models of acute versus chronic brain ER stress in obesity/T2D syndrome. Pathological conditions associated with obesity and T2D induce both acute and chronic ER stress in the brain. Acute brain ER stress rapidly up-regulates the sympathetic nervous system activity to cause peripheral insulin resistance, glucose intolerance, and related BP dysregulation. Chronic brain ER stress, on the other hand, disrupts the hypothalamic neuroendocrine functions to cause eating disorder, overweight, and obesity. These neural and neuroendocrine processes are physiologically interconnected and are affecting each other at multiple levels; the combined effects of these two processes represent a significant CNS basis for body weight-independent and body weight-dependent development of T2D and related problems.