Metaflammation

Chronic metabolic inflammation, Metaflammation, is a critical component of obesity and plays a critical role in metabolic pathologies such as insulin resistance and diabetes. During our studies exploring the mechanisms underlying the emergence of obesity-associated chronic inflammatory and stress responses such as JNK activation, we discovered abnormal ER adaptive responses and activity profiles in both experimental and human obesity.  These studies suggested that ER stress and dysfunction may be proximal to emergence of metaflammation.  In fact, most recently, we discovered that in adipose tissue, abnormal ER calcium homeostasis is a critical trigger for inflammation- and obesity-related JNK activation and impaired insulin action in adipose tissue and abnormal systemic glucose metabolism.  These discoveries support a model that ER dysfunction and stress is a critical instigator of metaflammation.