Table 1.

Mechanisms responsible for obesity-induced adipokines dysfunction and their roles in obesity-related HCC.

Adipokines	Functions	Tendency in obesity	Inducers	Effects on HCC	Molecular mechanisms	References
Anti-inflammatory
Adiponectin	Increases insulin sensitivity Relieves inflammation Eliminates HCC cells	Downregulated	Insulin resistance Hypoxia microenvironment Chronic inflammation	Inhibits	AMPK/TSC2/mTOR↑, Caspase-3↑, JNK↑, STAT3↓, PI3K/Akt↓, SOCS3↑, TNF-α↓.	(20–22, 24–29)
Ghrelin	Regulates energy steady state Maintains healthy liver function Reduces lipid toxicity	Downregulated	Insulin resistance Positive energy balance	Inhibits	NF-ĸB↓, TNF-α↓, TG↓.	(30–33)
Irisin	Improves glucose homeostasis Improves insulin resistance Induces weight loss	Downregulated	Lack of exercise T2D	Inhibits	De novo lipogenesis↓	(31, 34, 35)
Pro-inflammatory
Leptin	Regulates the appetite and energy balance Resists weight gain Promotes hepatic steatosis	Upregulated	Lipotrophy Chronic inflammation	Promotes	JAK2/STAT3↑, PI3K/Akt↑, ERK↑, p53/FOXO3A↑	(24, 28, 36, 37)
Resistin	Antagonizes insulin Induces hepatic insulin resistance	Upregulated	Insulin resistance Central/visceral obesity	Promotes	p38 MAPK/NF-κB↑	(38–41)
Visfatin	Exerts insulin-like hypoglycemic effect Promotes adipose expansion Hepatic inflammation	Upregulated	Insulin resistance	Promotes	NF-ĸB↑, STAT3↑, PI3K/Akt↑, ERK↑	(31, 42–47)