Their current findings pinpoint STAMP2 as a critical factor to prevent overt inflammatory responses during everyday nutrient fluctuations or conditions of nutrient excess. In fat cells, a lack of STAMP2 led to aberrant inflammatory responses to both nutrients and acute inflammatory stimuli, they reported.
Similarly, they showed that the visceral fat surrounding the internal organs of STAMP2-deficient mice became inflamed, and the animals developed spontaneous metabolic disease on a regular diet, manifesting insulin resistance, glucose intolerance, high blood sugar and lipid levels, and fatty liver disease. They also showed that the loss of STAMP2 exacerbated the metabolic symptoms of mice with a genetic predisposition to obesity due to other factors.
When food enters the system, STAMP2 normally keeps the immunity response "button" from getting pushed, Hotamisligil said.
"We suggest that, over time, the accumulation of small cellular stresses due to daily changes and fluctuations in nutrients in STAMP2-deficient mice may lead to the activation of inflammatory pathways and inhibition of insulin action, resulting in systemic metabolic deterioration over the long term," he continued.