With the unprecedented obesity epidemic, nonalcoholic steatohepatitis (NASH) now becomes a major chronic liver disorder, affecting 3-5% of the global population. NASH is an advanced form of nonalcoholic fatty liver disease (NAFLD)—a spectrum of chronic liver disorders that originate from benign fatty liver (simple steatosis) that can further progress into NASH, cirrhosis and even hepatocellular carcinoma (HCC). It is well-established that chronic liver inflammation is the key switch that drives simple steatosis transition into NASH. However, how dietary obesity licenses the establishment of chronic inflammation in the liver remains elusive. We aim to uncover the fundamental mechanisms by which chronic liver inflammation is established in the liver under obesity. By deploying a combination of biochemical, genetic, molecular, immunological, imaging, and histochemical tools as well as single-cell “omics” analyses, our ultimate goal is to reveal the fundamental molecular mechanisms underlying chronic liver inflammation and explore if such novel mechanistic insights could be applied to benefit liver repair and regeneration processes after injury, thereby preventing NAFLD progression into NASH/HCC.