Review of Obesity and Cancer—Reply
In Reply We thank Dr Huang and colleagues for their interest in our translational science Review on obesity and cancer. They submit that hepatocarcinogenesis is less attributable to the mechanisms disrupted by obesity and more related to chronic metabolic liver injury—including steatosis, inflammatory activity, insulin resistance, and fibrosis. Although we agree that fibrosis and cirrhosis…
We extend our gratitude to Dr. Huang and colleagues for their interest in our translational science Review on obesity and cancer. While they argue that hepatocarcinogenesis is primarily due to chronic liver injury stemming from obesity, we concur that fibrosis and cirrhosis are significant factors contributing to the risk of hepatocellular carcinoma (HCC).
However, the core mechanisms highlighted in our Review remain closely linked to obesity. Research conducted by Park et al. reveals that obesity acts as a tumor promoter, accelerating inflammation and steatosis, rather than merely converging with these processes. In lean mice, the presence of obesity alone does not lead to HCC; however, nearly 90% of obese mice developed HCC under similar conditions, indicating that obesity has a hepatocellular carcinoma-promoting effect akin to the impact of the drug phenobarbital, a known carcinogen.
Moreover, the removal of interleukin 6 or tumor necrosis factor 1 receptor in obese mice resulted in the elimination of liver lipid, macrophage, and neutrophil accumulation. This evidence underscores that the heightened proinflammatory cytokines and altered signaling pathways implicated in our Review directly contribute to both hepatosteatosis and steatohepatitis, ultimately leading to liver tumorigenesis.
Written by urgent.news from JAMA's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
