Turning off insulin signals in the back part of the liver cuts fat without making the body pump out more insulin.

When insulin doesn’t work in the back part of the liver, the body doesn’t respond by making more insulin—even though fat in the liver goes down.

When the front part of the liver doesn’t respond to insulin, the body makes more insulin to try to compensate.

When the front part of the liver can't respond to insulin, blood sugar goes up—even if the liver makes less fat.

Turning off insulin signals in the back part of the liver doesn’t make blood sugar go up, even when the mouse eats a high-fat diet.

Hepatic lipid accumulation impairs insulin signaling and glucose metabolism, acting as a primary driver of systemic insulin resistance.