Chronic liver inflammation causes insulin resistance in various tissues, including skeletal muscle (SM); nevertheless, the underlying processes are largely unclear. The expression of hepatokine endoplasmic reticulum aminopeptidase 1 (ERAP1) was elevated by an HFD in primary hepatocytes from wild-type mice fed a long-term high-fat diet (HFD), which causes severe chronic inflammation and insulin resistance. ERAP1 levels were likewise elevated in interferon-treated primary hepatocytes.
Furthermore, overexpression of hepatic ERAP1 reduced systemic and SM insulin sensitivity, but knockdown of hepatic ERAP1 had the opposite effect, matching alterations in serum ERAP1 levels. Chronic inflammation in the liver causes insulin resistance in other tissues, including skeletal muscle (SM); nevertheless, the underlying processes are largely unclear. RNA sequencing of primary hepatocytes from wild-type mice given a long-term high-fat diet (HFD), which causes severe chronic inflammation and insulin resistance, indicating that an HFD increased the expression of hepatokine endoplasmic reticulum aminopeptidase 1 (ERAP1). ERAP1 levels were similarly shown to be higher in interferon-treated primary hepatocytes. Furthermore, hepatic ERAP1 overexpression reduced systemic and SM insulin sensitivity, whereas hepatic ERAP1 knockdown had the opposite impact, with matching alterations in serum ERAP1 levels.
