Proper regulation and management of energy, substrate diversity, and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, pathogenic signals are recognized and eliminated, and tissue homeostasis is safeguarded. These two ancient and vital systems interact at many levels and play a critical role in both physiology and pathology, particularly in chronic metabolic diseases. Metaflammation, a metabolically orchestrated, chronic, non-resolving, low-grade inflammation in critical metabolic organs is central to impaired metabolic homeostasis and sets the stage for obesity- and age-associated pathologies, such as chronic inflammation, dyslipidemia, and insulin resistance, and leads to diabetes, fatty liver disease, cardiovascular and respiratory problems, cancer and others.
These are supplemental materials for the papers entitled ”Inflammation, metaflammation, and immunometabolic disorders” and Foundations of immunometabolism and implications for metabolic health and disease” by Gokhan Hotamisligil, MD, PhD
Here, we examine decades of research identifying the complex immunometabolic signaling networks and the cellular and molecular events that occur in the setting of altered nutrient and energy exposures and offer a historical perspective.