Anti-lipogenic Activity Research Articles

Icaritin, a metabolite of Icarrin, Alleviates non-alcoholic fatty liver disease via inhibition of lipogenesis and ER stress

Non-alcoholic fatty liver disease (NAFLD) is one of the most serious global public health concerns. However, there are currently no effective drugs for treatment of this disease. Icariin (ICA), a small-molecule natural product extracted from Epimedium brevicornu Maxim, offers various pharmacological activities. In the present work, we wondered whether ICA can attenuate NAFLD in db/db mice treated with ICA for 8 weeks and how ICA exerts an influence on NAFLD. In db/db mice, ICA treatment had a robust effect on inhibition of lipogenesis associated with NAFLD amelioration by decreasing liver lipid deposition, together with ameliorating insulin sensitivity, glucose tolerance, and fasting serum glucose. Of note, ICA-treated rats showed a much higher concentration of icaritin (ICT) in plasma, a major metabolite of ICA, about 2000 times higher than that of ICA by liquid chromatography mass spectrometry (LC-MS). Interestingly, ICT, rather than ICA, can dramatically decrease hepatic lipogenesis-related markers in oleate acid/palmitate acid (OA/PA)-induced steatosis in primary hepatocytes (PH) and HepG2 cells, and hepatic lipid accumulation in db/db mice, demonstrating the inhibitory effect of ICT on lipogenesis. Mechanistically, we found that anti-lipogenic activities of ICT were related to reducing endoplasmic reticulum (ER) stress as evidenced by Western blot, qPCR, and other assays in thapsigargin (THP) induced-ER stress models. To our knowledge, this is the first report showing the unexpected and key role for ICT on the prevention of NAFLD in db/db mice through an ER stress mechanism.

Chlorogenic acid improves anti-lipogenic activity of metformin by positive regulating of AMPK signaling in HepG2 cells.

Metformin improves lipid profile, however, combination therapy is developing to increase its effectiveness and reduce the deleterious effects of metformin. Chlorogenic acid (CGA) has exhibited lipid-lowering effects. This study aimed to investigate the combined effect of metformin and CGA on lipid accumulation, as well as to elucidate the engaged mechanism in HepG2 cells. To find the non-lethal doses of metformin and CGA, MTT assay was performed. High Glucose (HG) at 33 mM was used to induce lipogenesis in HepG2 cells. Following treatment with different concentrations of metformin and CGA, total lipid content (Oil Red O-staining), triglyceride level, the genes expression of SREBP-1c and FAS, and phosphorylation of AMPK and ACC were measured. Both Metformin and CGA decreased HG-induced lipid accumulation individually, by decreasing total lipid content and triglyceride level. The lowest effective doses of metformin and CGA were 0.25 mM and 5 μM, respectively, which significantly reduced SREBP-1c and FAS genes expression. The combination of these concentrations reinforced these effects. The phosphorylation of AMPK and ACC were more increased by metformin in combination with CGA than both individually. Our findings suggest that CGA synergistically enhances metformin lipid reducing action via the regulating of involved factors in fatty acid synthesis. Therefore, co-administration of metformin with CGA may have further medical value in treating lipid metabolism disorders.

Subtilisin of Leishmania amazonensis as Potential Druggable Target: Subcellular Localization, In Vitro Leishmanicidal Activity and Molecular Docking of PF-429242, a Subtilisin Inhibitor.

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.

Tamarixetin Abrogates Adipogenesis Through Inhibiting p300/CBP-Associated Factor Acetyltransferase Activity in 3T3-L1 Preadipocyte Cells.

Tamarixetin (TX) is an O-methylated flavonoid naturally derived from quercetin. TX has bioactive properties; however, whether it shows antilipogenic activity remains unknown. Therefore, in the present study, we aimed to determine the antilipogenic effects of TX using 3T3-L1 adipocytes. The 3T3-L1 adipocytes were cultured in a differentiation medium with or without TX. Lipid accumulation was diminished and the mRNA expression of lipogenesis-related genes was decreased following TX treatment. We found that TX exhibited antilipogenic effects by inhibiting the expression of p300/CBP-associated factor (pCAF), a histone acetyltransferase, as confirmed by pCAF knockdown. Furthermore, TX inhibited both pCAF expression and its activity, thereby reducing the total acetylation level of nonhistone and histone proteins. Finally, TX decreased the expression of CCAAT/enhancer-binding protein alpha and beta (CEBPα and CEBPβ), and peroxisome proliferator-activated receptor γ along with pCAF expression during adipogenesis of 3T3-L1 cells in a time-dependent manner. Collectively, our findings suggest that TX is a potent antilipogenic agent derived from natural products and may be used as a pCAF inhibitor.

Bioactive extracts from persimmon waste: influence of extraction conditions and ripeness

In this work, a bioactive persimmon extract was produced from discarded fruits. A central composite design was used to evaluate the effect of different extraction parameters and ripeness stages of persimmon fruits on the total phenolic content and antioxidant activity of the resulting extracts. Significantly greater phenolic contents were obtained from immature persimmon (IP) fruits. The optimum IP extract with the conditions set by the experimental design was industrially up-scaled and its composition and functional properties were evaluated and compared with those obtained under lab-scale conditions. Both extracts contained significant protein (>20%) and phenolic contents (∼11-27 mg GA/g dry extract) and displayed significant antiviral activity against murine norovirus and hepatitis A virus. Moreover, the extract showed no toxicity and significantly reduced the fat content and the cellular ageing of Caenorhabditis elegans (C. elegans) without affecting the worm development. These effects were mediated by down-regulation of fat-7, suggesting an anti-lipogenic activity of this extract.

Structure and Biological Activity Analysis of Fucoidan Isolated from Sargassum siliquosum.

Fucoidans are heterologous polysaccharides commonly seen in brown macroalgae and are known for their biological activity including anticancer, antiangiogenic, immunomodulation, and antiviral properties. The brown macroalga Sargassum siliquosum was used for the extraction and analysis of fucoidan in this study. The S. siliquosum fucoidan was indicated as a galactofucoidan composed of sugars, uronate, and sulfate at a ratio of 12:1:4 and its purity was 85% based on the abovementioned three major components. Structural analysis by electrospray ionization collision-induced dissociation tandem mass spectroscopy revealed that the purified fucoidan consisted of a carbohydrate chain composed of (1→3)-linked or (1→4)-linked l-fucose residues, with sulfate groups at C-2 and C-4 positions. Galactose residues with (1→4)-linkages function as the branch points and they are located at the C-3 or C-4 position of fucose residues. Galactose residues are sulfated mainly at C-4 and C-6, while some sulfation can also be seen at C-2. The fucoidan purified from S. siliquosum demonstrated antioxidant, anti-inflammatory, and antilipogenic activities.

Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation.

The identification of new probiotics with anti-obesity properties has attracted considerable interest. In the present study, the anti-obesity activities of Akkermansia muciniphila (A. muciniphila) strains isolated from human stool samples and their relationship with the gut microbiota were evaluated using a high fat-diet (HFD)-fed mice model. Three strains of A. muciniphila were chosen from 27 isolates selected based on their anti-lipogenic activity in 3T3-L1 cells. The anti-lipogenic, anti-adipogenic and anti-obesity properties of these three strains were evaluated further in HFD-induced obese mice. The animals were administered these strains six times per week for 12 weeks. The treatment improved the HFD-induced metabolic disorders in mice in terms of the prevention of body weight gain, caloric intake and reduction in the weights of the major adipose tissues and total fat. In addition, it improved glucose homeostasis and insulin sensitivity. These effects were also associated with the inhibition of low-grade intestinal inflammation and restoration of damaged gut integrity, prevention of liver steatosis and improvement of hepatic function. These results revealed a difference in the distribution pattern of the gut microbial communities between groups. Therefore, the gut microbial population modulation, at least in part, might contribute to the beneficial impact of the selected A. muciniphila strains against metabolic disorders.

Microbial Metabolites of Gallotannins Suppress Inflammation in RAW 264.7 Macrophages Through the Modulation of the AMPK/NF-kb Axis

Abstract Objectives Obesity has been positively correlated with alterations in adipose tissue such as increased production of pro-inflammatory molecules and high content of adipose tissue macrophages. In previous in vitro studies, we have shown that microbial metabolites of gallotannins (GT), including gallic acid (GA) and pyrogallol (PG), possess anti-inflammatory activities in cancer cells, as well as anti-lipogenic activities in adipocytes. In this study, we explored the molecular mechanisms of microbial metabolites of GT by investigating the effect of GA and PG on the inflammatory cytokines expression, AMP-activated protein kinase (AMPK) and NF-kb signaling pathways in RAW 264.7 macrophages. Methods RAW 264.7 macrophages were pre-treated with GA or PG (2.5 and 5 mg/L). Afterwards, inflammation was induced by 1 mg/mL lipopolysaccharide (LPS) along with the previous treatment. In a separate experiment, RAW 264.7 cells were pre-treated with or without 10 mM Compound C, an AMPK activity inhibitor, along with GA or PG (5 mg/L) and incubated with 1 mg/mL LPS. Analyses of gene and protein expression of inflammatory cytokines, AMPK and NF-kb were performed using qPCR and Western blot. Results mRNA and protein expressions of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were significantly decreased in LPS-treated RAW 264.7 macrophages by GA and PG. Additionally, GA and PG inhibited LPS-induced inflammation through the up-regulation of AMPK and sirtuin 1 (Sirt1) activities, and the down-regulation of NF-kb activity. AMPK inhibition by Compound C in RAW 264.7 macrophages partially blocked LPS-induced inflammatory signaling. As a result, the inhibitory effects of GA and PG on LPS-induced inflammation were weakened. Conclusions GA and PG attenuate inflammation in RAW 264.7 macrophages at least in part through the activation of the AMPK pathway and the suppression of NF-kb activity. Overall, microbial metabolites of GT might possess therapeutic potential in the prevention of obesity-related adipose tissue inflammation. Funding Sources COALS's Nutrition Obesity Strategic Fellowship at Texas A&M University.

Fucoxanthin Ameliorates Atopic Dermatitis Symptoms by Regulating Keratinocytes and Regulatory Innate Lymphoid Cells.

Fucoxanthin (FX) is a xanthophyll that is contained abundantly in marine plants. The biological action of FX includes its antioxidant and anti-lipogenic activities, while the precise action of its mechanisms on skin cells has not yet been clarified. The current study examined the effect of FX in comparison with tacrolimus (TAC) on NC/Nga mice, which are an atopic dermatitis (AD) model. FX topical treatment dramatically ameliorated itching behavior over the TAC treatment, which was insufficient for improvement of AD symptoms. In Nc/Nga mice, FX or TAC applied to the skin inhibited eosinophil infiltration with decreased expression of Il-33. FX also stimulated Il-2, Il-5, Il-13, Il-10, and TGF-β expression levels, and Sca1+Il-10+TGF-β+ regulatory innate lymphoid cells (ILCreg) were dominantly observed in FX treated skin epidermal keratinocytes and dermal layers. This combined evidence demonstrated that FX exerts anti-inflammatory effects on keratinocytes and ameliorates AD symptoms by regulating ILCreg to normalize immune responses in an atopic dermatitis model.

N-Butanol Extract of Lotus Seeds Exerts Antiobesity Effects in 3T3-L1 Preadipocytes and High-Fat Diet-Fed Mice via Activating Adenosine Monophosphate-Activated Protein Kinase.

In this study, the antiobesity effects of n-butanol extract of lotus seeds (LBE) were evaluated in cultured 3T3-L1 preadipocytes and in high-fat diet (HFD)-fed mice. LBE decreased lipid contents in mature 3T3-L1 cells without obvious cytotoxicity. Meanwhile, LBE supplementation also led to weight loss and improved plasma lipid profiles in HFD-fed mice. Furthermore, LBE could activate AMP-activated protein kinase (AMPK) accompanied by down-regulation of lipogenesis related genes (PPARγ, aP2, LPL, C/EBPα, FAS, SREBP-1c) and up-regulation of lipolysis genes (adiponectin and PPARα) in vitro and in vivo. Collectively, our data demonstrated LBE possesses antiadipogenic and antilipogenic activities which are, at least partially, mediated by the activation of AMPK signaling pathways.

Evaluation of lipotropic effect of herbal formulation on hepatic fat accumulation in rats fed with methionine-choline deficient diet

Background: Choline is an essential lipotropic nutrient for regulating fatty acid synthesis and hepatic lipid mobilization. Deficiency of choline causes fatty liver leading to dysregulated liver function. Objective: To investigate the lipotropic activity of the proprietary herbal formulation (PHF) containing Acacia nilotica and Curcuma longa. Materials and Methods: Fatty liver disease was induced in Wistar rats by feeding methionine/choline-deficient (MCD) diet for 4 weeks. Animals were concurrently treated with PHF (at 50, 100, 200, and 400 mg/kg rat body weight/day) for 4 weeks. Methionine/choline-sufficient (MCS) diet-fed rats were used as control. Serum biochemistry and liver parameters were determined at the end of experimental period. Further, anti-lipogenic and lipolytic activity of PHF extract was studied in HepG2 cells. Results: Rats fed with MCD diet, showed significant increase in liver lipids, triglycerides, cholesterol, thiobarbituric acid reactive substance, and serum alanine transaminase (ALT) and decreased serum triglyceride level compared to MCS diet-fed rats indicating significant fat accumulation and liver damage. PHF treatment significantly decreased the liver lipids, triglyceride and serum ALT compared to MCD diet-fed rat. Histological evaluation revealed the restoration of hepatic architecture after PHF treatment. In in vitro studies, the PHF extract decreased the oleic acid induced fat accumulation in HepG2 cells. Conclusion: The study demonstrated the lipotropic effect of PHF evident from decreased fat accumulation and antilipogenic activity. These data suggests that PHF could be a potential supplement for preventing fatty liver.

Lipogenesis inhibition and adipogenesis regulation via PPARγ pathway in 3T3-L1 cells by Zingiber cassumunar Roxb. rhizome extracts

Zingiber cassumunar (ZC) is used by tribal people in northern Thailand in traditional remedies for anti-obesity and in food recipes. Extracts from this plant have been studied for several pharmacological effects including anti-obesity, but with no clear evidence on cellular mechanism of activity. This study aim to investigate the lipolytic and anti-adipogenic activity of crude extracts from ZC on in vitro cultures of the mouse adipocyte cell-model, 3T3-L1. Dry rhizome powder was extracted with absolute ethanol and boiled-water. On the exposed pre-adipocytes to the extracts, cytotoxicity was not detected by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Lipid content and glycerol release were assessed using Oil Red-O and a commercial Adipolysis Assay kits respectively. The extracts exhibited no significant lipolytic activity on the exposed mature-adipocytes, in serial dilutions ranging from 1 to 800 µg/ml. However, anti-lipogenic activity was presented. All extracts significantly reduced the lipid content of exposed differentiating-adipocytes. This anti-lipogenic activity was confirmed by the expression of selected genes, determined by using real-time PCR techniques, in four groups namely: adipocyte differentiation genes, glucose uptake genes, lipid metabolism genes and fatty acid oxidation genes. 1H NMR spectrum of the extracts exhibited the prominent olefinic protons of phenylbutanoids, the group of compounds previously proved with several bioactivities. This study provided evidences of mechanisms that apparently verify the traditional use of ZC to prevent obesity.

A Blend of Extracts from Houttuynia cordata, Nelumbo nucifera, and Camellia sinensis Protects Against Ethanol-Induced Liver Damage in C57BL/6 Mice.

The protective activity of a mixture of aqueous and ethanolic extracts from Houttuynia cordata Thunb, Nelumbo nucifera G. leaves, and Camellia sinensis seed (HNC) was evaluated in C57BL/6 mice. Pretreatment with HNC prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase caused by ethanol-induced hepatic damage. The HNC-treated mice showed significantly lower triglyceride levels, reduced CYP2E1 activity, and increased antioxidant enzyme activities and lipogenic mRNA levels. These results suggest that HNC might be a candidate agent for liver protection against ethanol-induced oxidative damage, through enhancement of antioxidant and antilipogenic activity.

Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease.

BACKGROUND/OBJECTIVESNon-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD.MATERIALS/METHODSThe preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group.RESULTSEAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation.CONCLUSIONSAllium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.

Aged citrus peel (chenpi) extract reduces lipogenesis in differentiating 3T3-L1 adipocytes

Aged citrus peel (chenpi) is made from the dry peel of the fruit of Citrus reticulate Blanco after aging process. It has long been used as a food ingredient, a dietary supplement, and for medicinal purpose. Compared to fresh citrus peel extract, chenpi extract contains more 5-demethylated polymethoxyflavones (5-OH PMFs). To investigate a potential direct role of chenpi extract on adipose tissue, we examined the effect of chenpi extract on differentiating 3T3-L1 cells. We showed that two types of chenpi extract varying in 5-OH PMF contents consistently reduces intracellular lipid accumulation without significantly affecting cell viability and proliferation. The reduction in lipid accumulation is correlated with AMP-activated protein kinase (AMPK) activation and down-regulation of adipogenic transcription factors as well as lipogenic genes. The results indicate that chenpi extract may directly affect lipogenesis in adipose tissue and the content of 5-OH PMFs likely affects the anti-lipogenic activity of chenpi extract.

Pinus Densiflora Bark Extract (PineXol) Decreases Adiposity in Mice by Down-Regulation of Hepatic De Novo Lipogenesis and Adipogenesis in White Adipose Tissue

PineXol, extracted from Korean red pine bark, has beneficial effects, such as antioxidant, antiinflammatory, and antilipogenic activities in vitro. We tested the hypothesis that PineXol supplementation could have anti-obesity effects on mice fed a high-fat diet (HFD). Four-week-old male C57BL/6 mice were fed normal chow (18% kcal from fat) or a HFD (60% kcal from fat). HFD-fed animals were also subjected to PineXol treatment at a dose of 10 or 50 mg/kg body weight (BW) (PX10 or PX50, respectively) body weight. The body weight and body fat mass in the PX50 group were statistically lower than those in the HFD group (p < 0.05 and p < 0.001, respectively). The concentration of hepatic triglycerides, total cholesterol, and low-density lipoprotein cholesterol were reduced in the PX50 group compared with the HFD group (p < 0.01). Acetyl CoA carboxylase (p < 0.01), elongase of very long chain fatty acids 6 (p < 0.01), stearoyl CoA desaturase 1 (p < 0.05), microsomal triglyceride transfer protein (p < 0.01), and sterol regulatory element-binding protein 1 (p < 0.05) were significantly decreased in the PX50 group compared with that in the HFD group. In white adipose tissue, CCAATenhancer-binding protein alpha (p < 0.05), peroxisome proliferator-activated receptor gamma (p < 0.001), and perilipin (p < 0.01) were decreased in the PX50 group compared with those in the HFD group. Therefore, the current study implies the potential of PineXol for the prevention and/or amelioration of obesity, in part by inhibition of both hepatic lipid synthesis and adipogenesis in white adipose tissue.

Biotransformation effects on anti lipogenic activity of citrus extracts

Citrus peel is a good source of flavonoids, with higher content in relation to pulp. This study proposed to investigate the anti-lipogenic potential of a newly developed citrus flavonoids extract, obtained from citrus industrial residue, bioprocessed in order to generate a commercial source of some flavonoids naturally found in low quantity. The results showed that the citrus peel extract obtained after biotransformation was a good source of hesperitin and naringenin, flavonoids that has no source for production on a large scale, as in supplements or medicines. Still, the results showed that all extracts could be used in obesity treatment. The original extract, “In Natura”, would be useful to reduce new adipocytes synthesis and lipid accumulation, and the extract bioprocessed, “Biotransformed” extract could be used to induce lipolysis on fat tissue.

Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes

It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARγ, C/EBPα, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production.

Glycolytic switch in response to betulinic acid in non-cancer cells.

The naturally occurring triterpenoid betulinic acid (BA) shows pronounced polypharmacology ranging from anti-inflammatory to anti-lipogenic activities. Recent evidence suggests that rather diverse cellular signaling events may be attributed to the same common upstream switch in cellular metabolism. In this study we therefore examined the metabolic changes induced by BA (10 µM) administration, with focus on cellular glucose metabolism. We demonstrate that BA elevates the rates of cellular glucose uptake and aerobic glycolysis in mouse embryonic fibroblasts with concomitant reduction of glucose oxidation. Without eliciting signs of obvious cell death BA leads to compromised mitochondrial function, increased expression of mitochondrial uncoupling proteins (UCP) 1 and 2, and liver kinase B1 (LKB1)-dependent activation AMP-activated protein kinase. AMPK activation accounts for the increased glucose uptake and glycolysis which in turn are indispensable for cell viability upon BA treatment. Overall, we show for the first time a significant impact of BA on cellular bioenergetics which may be a central mediator of the pleiotropic actions of BA.

Effect of rutin on the accumulation of lipid in H4ⅡE hepatoma cells

Rutin is a flavonoid compound present within various plants. Previous studies have suggested that rutin has a potential antidiabeticand a anti-cancer activity in a few experimental models. However, it is uncertain that rutin can affect hepatic lipidaccumulation, which is a pathophysiological marker of steatohepatitis (fatty liver) in metabolic syndrome. The present studyinvestigated the effect of rutin on the intracellular accumulation of lipid induced by palmitic acid in H4IIE rat hepatoma cells.Rutin significantly suppressed palmitic acid-induced lipid accumulation whereas other flavonoid compound (hesperidin) did not.Protein content of the key enzyme in the biosynthesis of triglyceride, FAS, was decreased by rutin. The number of intracellularlipid droplets was also suppressed by rutin. Taken together, rutin has a strong anti-lipogenic activity, indicating thepharmacological potential to treat one of metabolic syndrome.