Proteasome dysfunction mediates obesity-induced endoplasmic reticulum stress and insulin resistance in the liver
T Otoda, T Takamura, H Misu, T Ota, S Murata… - Diabetes, 2013 - Am Diabetes Assoc
Chronic endoplasmic reticulum (ER) stress is a major contributor to obesity-induced insulin
resistance in the liver. However, the molecular link between obesity and ER stress remains
to be identified. Proteasomes are important multicatalytic enzyme complexes that degrade
misfolded and oxidized proteins. Here, we report that both mouse models of obesity and
diabetes and proteasome activator (PA) 28-null mice showed 30–40% reduction in
proteasome activity and accumulation of polyubiquitinated proteins in the liver. PA28-null …
resistance in the liver. However, the molecular link between obesity and ER stress remains
to be identified. Proteasomes are important multicatalytic enzyme complexes that degrade
misfolded and oxidized proteins. Here, we report that both mouse models of obesity and
diabetes and proteasome activator (PA) 28-null mice showed 30–40% reduction in
proteasome activity and accumulation of polyubiquitinated proteins in the liver. PA28-null …