Research Article: Inflammatory cause of metabolic syndrome via brain stress and NF-κB

Date Published: February 11, 2012

Publisher: Impact Journals LLC

Author(s): Dongsheng Cai, Tiewen Liu.



Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today’s world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain.

Partial Text

Research in the past decade has established that metabolic syndrome can result from innate immune activation in response to overnutrition. While this type of inflammation exists broadly across different tissues, the CNS is in a primary and wide-impact position for the induction of metabolic syndrome by nutritional inflammation. An inflammatory state in brain regulatory centers such as the hypothalamus disrupts its metabolic sensing function, which in turn affects downstream neural and neuroendocrine regulation of a wide range of physiological processes such as energy balance, glucose metabolism, and cardiovascular homeostasis. Dysregulations of these processes often happen concurrently and manifest as a cluster of highly associated metabolic disorders such as obesity, insulin resistance, and hypertension. Research in the past few years has significantly differentiated the hypothalamic inflammatory pathways underlying these metabolic disorders, and overnutrition-induced intracellular stresses have been recognized as key activators of metabolic inflammation in the hypothalamus. This new knowledge not only provides a conceptual framework for further dissecting the pathogenesis of metabolic syndrome related diseases, but also indicates potential interventional strategies of counteracting neuroinflammation against metabolic diseases. Regardless of this exciting status quo, many important questions still remain to be addressed experimentally. It is fair to say that current understandings on the central inflammatory mechanisms of metabolic syndrome and related diseases are still in a primitive stage. However, in light of its great significance from both biomedical research and therapeutic application perspectives, we expect major research endeavors being drawn to this field and more advances being made in the near future. We also anticipate that eventually these findings will be translated into novel and effective treatments/preventions against miscellaneous overnutrition-induced metabolic diseases.