Schisandrin B: A Double-Edged Sword in Nonalcoholic Fatty Liver Disease

Table 1

Physiological/pathological effects of adipokines/cytokines in nonalcoholic fatty liver disease (NAFLD).

Adipokines/cytokines	Site of secretion	Normal physiological functions	Pathological effects in NAFLD	References
Leptin	White adipose tissue	Preserves the insulin sensitivity in the liver [48] (via the cross talk with the insulin signaling by activating the suppressor of cytokine signaling 3 [49])	Proinflammatory and fibrogenic [50] (via the activation of HSCs)	[48–50]
Adiponectin	Adipose tissue	Improves fatty acid metabolism by the induction of free fatty acid oxidation as well as inhibition of gluconeogenesis, free fatty acid uptake, and de novo lipogenesis in cultured hepatocytes [53]	The level of adiponectin is reduced in NAFLD [52]	[52–54]
	Injured hepatocytes	Suppresses the release of proinflammatory cytokines (TNF-α and IL-6) and induces the release of the anti-inflammatory cytokine (IL-10) in Kupffer cells [54]
		Elicits an antifibrotic response by the inhibition of the release of TGF-β [54]
Resistin	Macrophage-infiltrating adipose tissue [56]		Induces glucose intolerance and insulin resistance [55]	[55–61]
			Proinflammatory (the induction of release of TNF-α, IL-1β, IL-6, and IL-2 in resistin-incubated macrophages) [58–60]
			Induces hepatic fibrosis (via the activation of HSCs and Kupffer cells [61] which release TGF-β and form collagen type 1)
Visfatin	Macrophage-infiltrating adipose tissue [56]		Possesses nicotinamide phosphoribosyl-transferase activity, which is critical for the glucose-induced release of insulin in pancreatic beta cells in vitro and in vivo [63]	[56, 63, 64]
			Proinflammatory (the release of TNF-α, IL-6, and IL-1β from macrophages [64])
TNF-α and IL-6	Adipocytes in individuals with insulin resistance or obesity [65]		Associated with the extent of obesity/adiposity in patients [66, 67]	[65–70]
			Distally influence the metabolic functions of liver via the JNK1-mediated release of IL-6 [68]
			Facilitate the development of NASH and HCC (via the induction of oncogenic factor STAT3 and release of TNF-α and IL-6) [70]

HSCs: hepatic satellite cells; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; IL-10: interleukin-10; TGF-β: transforming growth factor-β; IL-2: interleukin-2; IL-1β: interleukin-1β; JNK1: c-Jun N-terminal kinase-1; NASH: nonalcoholic steatohepatitis; HCC: hepatocellular carcinoma; STAT3: signal transducer and activator of transcription-3.