Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Table 2 Studies and their findings on leptin

Study	Finding	Ref.
Human	Leptin levels higher in obese individuals and increased with overfeeding	[82,83]
	Higher leptin levels in women independent of fat mass	[104-107]
	Body mass index and IR strongly correlated with leptin levels	[84]
	Central obesity correlated with higher leptin levels in comparison with non-central obesity	[86]
	Administration of leptin to individuals with lipoatrophic diabetes resulted in reduction of triacylglycerol concentrations, liver volume, glycated hemoglobin and discontinuation, or a large reduction in antidiabetes therapy	[89]
	Leptin inhibited insulin secretion and transcription of the preproinsulin gene	[87]
	IR associated with elevated plasma leptin levels independently of body fat	[110]
	Leptin/adiponectin ratio predicted T2DM in both sex	[111]
	Leptin C2549A AA genotype found at a higher rate in T2DM	[114]
	Leptin levels significantly higher in NASH, and correlated with the severity of hepatic steatosis, but not with the grade of necroinflammation or fibrosis	[116-118]
	Leptin not found as a predictor of histological severity of NASH	[119]
	No significant difference in leptin concentrations between NASH patients and controls, or in connection to the severity of liver fibrosis	[120,121]
	IR and low leptin levels predictors of steatosis in the liver	[122]
Animal	Mice lacking the ob gene became severely obese	[91]
	Leptin infusion attenuated hepatic steatosis and hyperinsulinemia	[92]
	Mice without leptin signaling had an increased lipid accumulation in liver	[93]
	Leptin prevented lipid accumulation in nonadipose tissue through SREBP-1 modulation	[94]
	After long-term exposure to high-fat diet (> 20 wk), mice resistant to leptin even when directly infused into the brain	[95-98]
	Hyperleptinemia itself contributed to leptin resistance by down regulating cellular response to leptin	[99]
	Mice with poly (ADP-ribose) polymerase-1 deficiency susceptible to diet-induced obesity, hyperleptinemia, and IR	[115]
	Leptin-deficient, insulin-resistant mice developed leptin resistance on a high fat diet independently of hyperleptinemia, c-Jun N-terminal kinase inflammatory pathway relevant in the induction of diet-induced glucose intolerance	[100]
	Leptin increased expression of procollagen-I, transforming growth factor beta1, smooth muscle actin and TNF-α and thus increased liver fibrosis and inflammation	[101]
	Leptin-resistant mice exhibited significantly reduced fibrogenic response	[102,103]
In vitro	Fibrogenic effect of leptin accomplished through hepatic stellate cells, leptin a potent mitogen and apoptosis inhibitor	[23]

IR: Insulin resistance; T2DM: Type 2 diabetes mellitus; NASH: Nonalcoholic steatohepatitis; SREBP-1: Sterol regulatory element-binding protein 1; ADP-ribose: Adenosine diphosphate ribose.