Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate–activated protein kinase in human HepG2 cells and obese mice

Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Nutrition research (Impact Factor: 2.47). 12/2011; 31(12):896-906. DOI: 10.1016/j.nutres.2011.09.026
Source: PubMed


Purple sweet potato is a functional food rich in anthocyanins that possess disease-preventive properties. Anthocyanins are known to possess potent antidiabetic properties. However, the effect of the anthocyanin fraction (AF) from purple sweet potato on hepatic lipid metabolism remains unclear. Our hypothesis is that AF inhibits hepatic lipid accumulation through the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in vitro and in vivo. In this study, we evaluated body weight, liver histology, and hepatic lipid content in high-fat diet (HFD)-fed ICR mice treated with AF. In addition, we characterized the underlying mechanism of AF's effects in HepG2 hepatocytes through Western blot analysis. Anthocyanin fraction (200 mg/kg per day) reduced weight gain and hepatic triglyceride accumulation and improved serum lipid parameters in mice fed an HFD for 4 weeks. Anthocyanin fraction significantly increased the phosphorylation of AMPK and acetyl-coenzyme A carboxylase (ACC) in the liver and HepG2 hepatocytes. In addition, AF down-regulated the levels of sterol regulatory element-binding protein 1 and its target genes including ACC and fatty acid synthase (FAS). The specific AMPK inhibitor compound C attenuated the effects of AF on the expression of lipid metabolism-related proteins such as SREBP-1 and FAS in HepG2 hepatocytes. The beneficial effects of AF on HFD-induced hepatic lipid accumulation are thus mediated through AMPK signaling pathways, suggesting a potential target for the prevention of obesity.

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    • "In addition, in some studies, animals were exposed to synthetic ACNs (i.e., cyanidin-3-O-β-glucoside) [50, 52, 56, 57], whereas in others they were exposed to extracts of ACN-rich foods (e.g., sweet potato, berries, and oranges) [27, 49, 58–62]. Mirroring the results obtained in vitro, there is ample convergence supporting an effect of ACNs in reducing hepatic lipid accumulation, that is, steatosis [49, 50, 52, 56–58, 60–63]. In addition, the majority of studies also reported an improvement in hepatic and systemic IR and serum lipids, often related to reduced weight gain [57, 58, 60–62]. "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD), defined by excessive lipid accumulation in the liver, is the hepatic manifestation of insulin resistance and the metabolic syndrome. Due to the epidemics of obesity, NAFLD is rapidly becoming the leading cause of altered liver enzymes in Western countries. NAFLD encompasses a wide spectrum of liver disease ranging from simple uncomplicated steatosis, to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Diet may affect the development of NAFLD either by increasing risk or by providing protective factors. Therefore, it is important to investigate the role of foods and/or food bioactives on the metabolic processes involved in steatohepatitis for preventive strategies. It has been reported that anthocyanins (ACNs) decrease hepatic lipid accumulation and may counteract oxidative stress and hepatic inflammation, but their impact on NAFLD has yet to be fully determined. ACNs are water-soluble bioactive compounds of the polyphenol class present in many vegetable products. Here, we summarize the evidence evaluating the mechanisms of action of ACNs on hepatic lipid metabolism in different experimental setting: in vitro, in vivo, and in human trials. Finally, a working model depicting the possible mechanisms underpinning the beneficial effects of ACNs in NAFLD is proposed, based on the available literature.
    Oxidative Medicine and Cellular Longevity 10/2013; 2013(1):145421. DOI:10.1155/2013/145421 · 3.36 Impact Factor
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    • "AMPK is a key sensor of cellular energy status [37], and platelet activation is an energy-consuming process. Our group, as well as other laboratories, recently demonstrated that anthocyanins affect AMPK phosphorylation in cells of several distinctive tissues [32], [38], [39], but their effect on platelet AMPK has not been explored. To determine whether Dp-3-g affects the phosphorylation of AMPK, which has recently been implicated in platelet signalling [40], platelet pAMPK levels were examined following collagen activation. "
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    ABSTRACT: Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs.
    PLoS ONE 05/2012; 7(5):e37323. DOI:10.1371/journal.pone.0037323 · 3.23 Impact Factor
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