Constant flow of nutrients and changing energy demands require a dynamic system to maintain metabolic homeostasis. As human living conditions and life expectancy change, systems that evolved to support short-term adaptation give rise to stress and inflammatory responses leading to metabolic deterioration. Inflammatory status is critical in obesity, insulin resistance and type 2 diabetes. Endoplasmic reticulum (ER) stress and activation of integrated stress and inflammatory signaling pathways such as the c-Jun N-terminal kinase (JNK) play critical roles in homeostasis. We are investigating the mechanisms through which nutrients and other metabolic cues couple to these pathways to modulate immune responses. We are also studying the mechanisms leading to ER dysfunction and how inflammatory and stress pathways relate to human disease with the goal of developing new potential therapeutics.