Additionally, although a key impact of this work is to demonstrate the role of hepatocyte MMP14 in hepatic steatosis, body weight gain, and inter-organ inflammatory responses, these findings provide one potentially translatable means to reduce hepatocyte MMP14 expression in diet-induced peripheral adiposity, glucose intolerance, liver TG accumulation, and inflammatory and fibrotic gene expression. Here, MMP14 is linked to fatty liver disease.