Nobiletin mitigates NAFLD via lipophagy and inflammation

Abstract

Nonalcoholic fatty liver disease (NAFLD), an increasingly serious health issue in the world, was characterized as lipid metabolic disorder without a satisfactory treatment. Nobiletin (NOB), a citrus flavonoid, was considered...

Current Advances in the Regulatory Effects of Bioactive Compounds from Dietary Resources on Nonalcoholic Fatty Liver Disease: Role of Autophagy

“…Nobiletin, a citrus flavonoid, has been shown to mitigate NAFLD in mice through TFEB-mediated lysosomal biogenesis and lipophagy . Consistently, Zhou et al found that phillygenin, a lignan from Forsythia suspensa , restored lipophagy and subsequently improved hepatic lipid deposition via Ca 2+ –calcineurin–TFEB axis.…”

“…It is widely accepted that the incidence of NAFLD is primarily attributed to sedentary lifestyles and the abundance of food. Under normal conditions, hepatic TG accumulation is the first and core step in the development of NAFLD, usually accompanied by IR and hyperlipidemia . There has been a decline in the fat synthesis and glucose uptake due to insufficient insulin sensitivity in adipose tissue and skeletal muscles in conditions of excess energy intake, followed by an increased amount of free fatty acids (FFAs) in the blood.…”

Polyphenols as NLRP3 inflammasome modulators in cardiometabolic diseases: a review ofin vivostudies

“…Although NLRP3 inflammasome activation plays a key role in all the selected cardiometabolic alterations, it plays an unequivocal role in the case of NAFLD, since it has been suggested that activation of the TLR4/NLRP3 pathway and the subsequent NLRP3 priming is involved in the onset of NAFLD and in the progression of this pathology to the characteristic fibrosis found in nonalcoholic steatohepatitis (NASH). 87,88 Table 4 summarizes the main findings from the seven studies [89][90][91][92][93][94][95] that were identified dealing with the modulation of the NLRP3 inflammasome by polyphenols regarding NAFLD. They comprised six preclinical studies and a clinical trial in NAFLD patients.…”

“…They comprised six preclinical studies and a clinical trial in NAFLD patients. 95 Regarding the selected animal models, one study was performed in rats fed an HFD, 89 while the other ones used the same diet either in wild type mice, [90][91][92][93] in ApoE −/− mice, 94 in C57BLKS/Lepr db mice 93 or in MARCKS (myristoylated alanine-rich C-kinase substrate)-deficient mice. 92 The studies tested phenolic compounds belonging to different categories: salisdroside (tyrosol glucoside), 93 a phenylpropanoid; carnosic acid, a phenolic terpene, 92 and salvianolic acid A, a phenolic acid; 89 quercetin, a flavonol; 91 and nobiletin, a flavone.…”

Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease

“…Multiple researches have reported the positive effects of NOB on NAFLD. For instance, NOB exerts an antisteatotic effect on the liver by regulating the expression of adiponectin receptor 1 and NADPH oxidase subunit gp91 phox30 restoring aberrant hepatic circadian rhythm, 31 enhancing lipophagy, 32 as well as targeting gut microbiota and myristoleic acid metabolism. 33 Moreover, our previous study also revealed that NOB mitigates the typical symptoms of NAFLD mice modeled by HFD through reducing the levels of hepatic lipids and serum proinflammatory cytokines.…”