Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells

Lin, Chih‐Li; Huang, Han-Pang; Lin, Jyh-Woei

doi:10.1194/jlr.m700128-jlr200

Cited by 172 publications

(159 citation statements)

References 34 publications

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“…Furthermore, the molecular mechanisms through which Scutellaria baicalensis acts are unknown. Recently, beneficial effects on obesity, diabetes and fatty liver have been reported for various flavonoids, which are thought to act through AMPK [9][10][11] . Therefore, the bioactive flavonoids such as baicalin in Scutellaria baicalensis are of particular interest.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, polyphenols have been reported to reduce hyperlipidemia and hyperglycemia, and their effects on lipogenesis have been suggested to be mediated via activation of the AMP-activated protein kinase (AMPK) [9][10][11] . In this relation, AMPK has emerged as an important regulator of lipid metabolism at the cellular and systemic levels, and dysfunction of hepatic AMPK represents a key mechanism for hepatic lipid accumulation and hyperlipidemia with hepatic steatosis in genetically obese rodents [12,13] and in high-fat-fed mice [13] and rats [9,14] . Consistent with this observation, transgenic mice expressing constitutively active Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet 1506 www.nature.com/aps Guo HX et al Acta Pharmacologica Sinica npg (CA)-AMPKα 1 in liver had reduced levels of white fat and were resistant to high-fat diet-induced obesity [15] .…”

Section: Introductionmentioning

confidence: 99%

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Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

et al. 2009

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Aim: Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated. Methods: Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined. Results: Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor α. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 µmol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose. Conclusion: Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

et al. 2009

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“…Oil red O staining (125 mM) was performed as previously described. 24,53 Images were acquired with the help of an Axiovert 35 microscope using the AxioVision Rel. 1.8 software.…”

Section: Methodsmentioning

confidence: 99%

p73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene

Agostini

et al. 2013

Cell Death Differ

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p73, a member of the p53 tumor suppressor family, is involved in neurogenesis, sensory pathways, immunity, inflammation, and tumorigenesis. How p73 is able to participate in such a broad spectrum of different biological processes is still largely unknown. Here, we report a novel role of p73 in regulating lipid metabolism by direct transactivation of the promoter of autophagy-related protein 5 (ATG5), a gene whose product is required for autophagosome formation. Following nutrient deprivation, the livers of p73-deficient mice demonstrate a massive accumulation of lipid droplets, together with a low level of autophagy, suggesting that triglyceride hydrolysis into fatty acids is blocked owing to deficient autophagy (macrolipophagy). Compared with wild-type mice, mice functionally deficient in all the p73 isoforms exhibit decreased ATG5 expression and lower levels of autophagy in multiple organs. We further show that the TAp73a is the critical p73 isoform responsible for inducing ATG5 expression in a p53-independent manner and demonstrate that ATG5 gene transfer can correct autophagy and macrolipophagy defects in p73-deficient hepatocytes. These data strongly suggest that the p73-ATG5 axis represents a novel, key pathway for regulating lipid metabolism through autophagy. The identification of p73 as a major regulator of autophagy suggests that it may have an important role in preventing or delaying disease and aging by maintaining a homeostatic control. Cell Death and Differentiation (2013) 20, 1415-1424; doi:10.1038/cdd.2013.104; published online 2 August 2013 p73 belongs to the p53 family, a group of transcription factors that have key roles in the regulation of many cellular processes, such as apoptosis, cell cycle, and senescence, especially following DNA damage. 1-3 Whereas p53 is a tumor suppressor and often either deleted or mutated in tumors, p73 is rarely mutated; however, its expression is often deregulated in cancer. 4,5 In p73-deficient mice, unlike in p53-deficient mice, no increase in spontaneous tumorigenesis is observed. 6 It has been demonstrated, however, that p73, in the absence of DNA damage, has a role in neuronal differentiation and development. 6-9 Consequently, p73-deficient mice exhibit neurological defects and, even though no obvious deficiencies in lymphoid or granulocyte populations have been so far detected, such mice show deregulated inflammatory responses and senescence. 6,10 Because of splicing events occurring near the 3 0 end of the coding region and because of an alternative promoter located in the third intron of the gene, p73 exists as multiple protein variants. 11 The isoforms containing a transactivation (TA) domain (TAp73s) generally behave like p53 with respect to overlapping promoters and biological functions. 2,4 For instance, in contrast to p73-deficient mice, TAp73 knockout mice showed spontaneous as well as carcinogen-induced tumors, indicating that TAp73 is a tumor suppressor. 12 The alternative promoter also produces amino-terminal truncated DN isoforms, the so-called ...

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“…It is noteworthy that LH can activate AMPK in the liver and muscle. AMPK is known to play a major role in energy homeostasis and is considered a key master switch regulating glucose and lipid metabolism (22). AMPK activation switches on ATP-producing processes and inhibits ATP-consuming anabolic processes (23).…”

Section: Discussionmentioning

confidence: 99%

Liver Hydrolysate Assists in the Recovery From Physical Fatigue in a Mouse Model

et al. 2013

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Abstract. It is reported that liver hydrolysate (LH) enhances liver function. However, the effects of LH on physical fatigue are unknown. The aim of this study was to investigate the effect of LH on alterations in locomotor activity and energy metabolism such as 5′-AMP-activated protein kinase (AMPK), glycogen content, and blood lactic acid, after forced walking. Adult male ddY mice were used. Locomotor activity, AMPK phosphorylation, and glycogen content in the liver and soleus muscle, as well as blood lactic acid were determined following LH treatment before and/or after forced walking. The locomotor activity significantly decreased after forced walking for 3 h. Two administrations of LH (30 or 100 mg/kg) significantly increased the locomotor activity, while a single administration either before or after forced walking did not show any specific effect. Administering LH twice activated AMPK in the liver and soleus muscle. Glycogen levels significantly decreased in both the liver and soleus muscle after forced walking, whereas the blood lactate level significantly increased. In contrast, administering LH twice increased muscle glycogen and decreased blood lactic acid. These findings indicate that LH produced an anti-fatigue effect and that this effect appears to involve the efficient glycogen utilization through activation of AMPK. [Supplementary Figure: available only at http://dx

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Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells

Cited by 172 publications

References 34 publications

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

p73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene

Liver Hydrolysate Assists in the Recovery From Physical Fatigue in a Mouse Model

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