Metabolic and inflammatory pathways crosstalk at many levels, and, while 
required for homeostasis, interaction between these pathways can also lead to 
metabolic dysregulation under conditions of chronic stress. Thus, we 
hypothesized that mechanisms might exist to prevent overt inflammatory responses 
during physiological fluctuations in nutrients or under nutrient-rich 
conditions, and we identified the six-transmembrane protein STAMP2 as a critical 
modulator of this integrated response system of inflammation and metabolism in 
adipocytes. Lack of STAMP2 in adipocytes results in aberrant inflammatory 
responses to both nutrients and acute inflammatory stimuli. Similarly, in whole 
animals, visceral adipose tissue of STAMP2(-/-) mice exhibits overt 
inflammation, and these mice develop spontaneous metabolic disease on a regular 
diet, manifesting insulin resistance, glucose intolerance, mild hyperglycemia, 
dyslipidemia, and fatty liver disease. We conclude that STAMP2 participates in 
integrating inflammatory and metabolic responses and thus plays a key role in 
systemic metabolic homeostasis.