Interdisciplinary studies in the research fields of endocrinology and immunology show that obesity-associated overnutrition leads to neuroinflammatory molecular changes, in particular in the hypothalamus, chronically causing various disorders known as elements of metabolic syndrome. In this process, neural or hypothalamic inflammation impairs the neuroendocrine and autonomic regulation of the brain over blood pressure and glucose homeostasis as well as insulin secretion, and elevated sympathetic activation was generally appreciated responsible. This review describes the involved physiology and mechanisms, with a focus on glucose and blood pressure balance, and suggests that neuroinflammation employs the autonomic nervous system to mediate the development of diabetes and hypertension.