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 represent important contributing factors to hepatocellular carcinoma risk that were beyond the scope of our pan-cancer Review, the remaining highlighted mechanisms are in fact closely tied to obesity. Park et al demonstrated that obesity functions as a tumor promoter that drives, rather than merely converges with, inflammation and steatosis. Under conditions in which carcinogen exposure does not induce hepatocellular carcinoma in lean mice, nearly 90% of obese mice developed hepatocellular carcinoma, confirming a carcinogenic effect of obesity that was comparable with treatment with phenobarbital, a known hepatocellular carcinoma tumor promoter. Importantly, ablation of interleukin 6 or tumor necrosis factor 1 receptor eliminated liver lipid, macrophage, and neutrophil accumulation in obese mice. Thus, the increased proinflammatory cytokines and altered signaling pathways described in our Review directly lead to both hepatosteatosis and steatohepatitis and, ultimately, liver tumorigenesis.