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

Table 1 Studies and their findings on adiponectin

Study	Finding	Ref.
Human	Adiponectin levels reduced in obese individuals	[25,34,35]
	Adiponectin levels higher in women	[36]
	Adiponectin levels reduced in T2DMHypoadiponectinemia associated with visceral fat accumulation	[37]
	High concentrations of adiponectin correlated with a decreased risk of developing T2DM	[41-43]
	Adiponectin mRNA decreased in obese T2DM	[40]
	SNP +45T>G genotypes and lower adiponectin level associated with higher FBG, insulin levels and HOMA-IR in obese women	[48]
	SNPs: 3971 A/G (rs822396), +276 G/T (rs1501299), -4522 C/T (rs822393) and Y111H T/C (rs17366743) significantly associated with hypoadiponectinemia	[49]
	High adiponectin/leptin ratio associated with lower plasma triglyceride, HOMA-IR and higher HDL	[44]
	Lower adiponectin levels an independent risk factor for NAFLD	[51]
	In human liver biopsies, hepatic adiponectin receptor mRNAs increased in biopsy-proven NASH	[52]
	Similar levels of adiponectin receptor mRNA in normal, steatotic liver and NASH	[53,54]
	Reduced AdipoR2 protein in NASH compared to steatotic liver	[55]
	Adiponectin levels lower in NASH and correlated with the progression of the disease	[56,70-72]
	HMW adiponectin isoforms increased after biliopancreatic diversion in obese subjects	[77]
Animal	Adiponectin lowers gluconeogenesis in the liver, increases fatty acid oxidation in muscle and reduces IR	[45]
	Disruption of both adiponectin receptors (adipo R1 and R2) increased tissue triglyceride content, inflammation, oxidative stress and IR	[46]
	Adiponectin enhanced the progression of hepatic steatosis, fibrosis, and hepatic tumor formation in NASH	[57]
	Adiponectin prevents lipid accumulation by increasing β-oxydation and by decreasing synthesis of FFA in hepatocytes in NASH	[47,58-60]
	Association of NAFLD and reduced expression of hepatic adiponectin receptors not consistently reported	[61,62]
	Peripheral injection of adiponectin resulted in reduction in body weight and improvement of peripheral IR	[47]
	Adiponectin reduced TNF-α and induced IL-10 release from Kupffer cells	[63]
	Pretreatment with adiponectin ameliorated D-galactosamine/LPS induced elevation of serum AST and ALT levels, and the apoptotic and necrotic changes in hepatocytes	[64]
In vitro	Adiponectin inhibited TNF-α induced expression of endothelial adhesion molecules and decreased LPS induced TNF-α production	[66]
	Adiponectin mediated anti-inflammatory activity by lowering NFκB action	[67]
	Adiponectin increased IL-8 and monocyte chemotactic protein-1 production, and activated the proinflammatory transcription factor NFκB	[68]
	Adiponectin acted antifibrotic through antagonizing leptin-induced STAT3 phosphorylation in activated hepatic stellate cell who promote fibrosis	[73]
	Lower HMW adiponectin closely associated with obesity-related metabolic complications and T2DM	[75]

T2DM: Type 2 diabetes mellitus; HOMA-IR: Homeostasis model assessment-estimated insulin resistance; FBG: Fasting blood glucose; HDL: High-density lipoprotein; NAFLD: Non-alcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; HMW: High-molecular weight; IR: Insulin resistance; FFA: Free fatty acids; TNF-α: Tumor necrosis factor alpha; IL-10: Interleukin-10; LPS: Lipopolysaccharide; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; IL-8: Interleukin-8; STAT-3: Signal transducer and activator of transcription 3.