Activation of Granulocytes in Response to a High Protein Diet Leads to the Formation of Necrotic Lesions in the Liver

In their aspiration to become healthy, people are known to follow extreme diets. However, the acute impact on organs regulating systemic metabolism is not well characterized. Here, we investigated the acute impact of six extreme diets on the liver in mice. Most diets did not lead to clear pathology after short-term feeding. However, two weeks of feeding with a high protein diet (HPD) resulted in an acute increase of liver enzymes in the blood, indicative of liver damage. Histology revealed the formation of necrotic lesions in this organ which persisted for several weeks. Flow cytometric analysis of hepatic immune cell populations showed that HPD feeding induced activation of macrophages and neutrophils. Neutralization of the pro-inflammatory cytokine IL-1 beta or depletion of macrophages with clodronate-loaded liposomes or with genetic models did not ameliorate liver necrosis. In contrast, the depletion of neutrophils prevented HPD-induced hepatic inflammation. After prolonged feeding, HPD-feeding was associated with a strong increase of the cytokines IL-10 and IL-27, suggesting that anti-inflammatory mediators are activated to prevent nutrient-overload-induced damage to the liver. In summary, whereas our data indicates that most extreme diets do not have a major impact on the liver within two weeks, diets with a very high protein content may lead to severe, acute hepatic damage and should therefore be avoided.

Automated summary

In their pursuit of health, people often adopt extreme diets, but the acute impact of these diets on the liver is not well understood. A study on mice found that a high protein diet (HPD) led to liver damage, with an increase in liver enzymes and the formation of necrotic lesions. The activation of macrophages and neutrophils was observed, and the depletion of neutrophils prevented liver inflammation. Prolonged HPD feeding resulted in an increase of anti-inflammatory mediators, suggesting a protective response. In conclusion, extreme diets may not have a major impact on the liver within two weeks, but diets with high protein content should be avoided to prevent severe acute liver damage.