Liver Zones and Fat: A Tale of Two Areas
286-OR: Spatial Regulation of Glucose and Lipid Metabolism by Hepatic Insulin Signaling
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
The liver has two zones: one near the entrance (periportal) and one near the exit (pericentral). Turning off insulin signals in the exit zone cuts fat there without raising blood sugar. Turning it off at the entrance cuts fat too—but makes blood sugar and insulin go up.
Surprising Findings
Pericentral insulin resistance reduced liver fat without triggering hyperinsulinemia or hyperglycemia.
Everyone assumes insulin resistance = bad. But here, insulin resistance in a specific liver zone actually improved metabolic health—contradicting the dogma that liver fat always drives systemic insulin resistance.
Practical Takeaways
If you have fatty liver, focus on improving muscle insulin sensitivity (via strength training and protein intake)—this study suggests muscles can compensate for liver dysfunction.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
The liver has two zones: one near the entrance (periportal) and one near the exit (pericentral). Turning off insulin signals in the exit zone cuts fat there without raising blood sugar. Turning it off at the entrance cuts fat too—but makes blood sugar and insulin go up.
Surprising Findings
Pericentral insulin resistance reduced liver fat without triggering hyperinsulinemia or hyperglycemia.
Everyone assumes insulin resistance = bad. But here, insulin resistance in a specific liver zone actually improved metabolic health—contradicting the dogma that liver fat always drives systemic insulin resistance.
Practical Takeaways
If you have fatty liver, focus on improving muscle insulin sensitivity (via strength training and protein intake)—this study suggests muscles can compensate for liver dysfunction.
Publication
Journal
Diabetes
Year
2025
Authors
Baiyu He, Kyle D. Copps, Morris F White, Rongya Tao
Related Content
Claims (10)
Hepatic lipid accumulation impairs insulin signaling and glucose metabolism, acting as a primary driver of systemic insulin resistance.
The liver isn’t the same all the way through—different parts react differently when insulin stops working, leading to very different outcomes for fat and sugar.
When mice eat a high-fat diet, fat builds up in both parts of the liver—but blocking insulin in just one part stops fat from building up there.
Where in the liver insulin resistance happens determines whether it causes high blood sugar, high fat, or neither.
When the part of the liver that usually responds to insulin is blocked, the liver makes less fat even when the mouse eats a high-fat diet—but its blood sugar and insulin go up instead.