Isohumulones, Bitter Acids Derived from Hops, Activate Both Peroxisome Proliferator-activated Receptor α and γ and Reduce Insulin Resistance

Yajima, Hiroaki; Ikeshima, Emiko; Shiraki, Maho; Kanaya, Tomoka; Fujiwara, Daisuke; Odai, Hideharu; Tsuboyama-Kasaoka, Nobuyo; Ezaki, Osamu; Oikawa, Shinichi; Kondö, Keiji

doi:10.1074/jbc.m403456200

Cited by 151 publications

(141 citation statements)

References 37 publications

(44 reference statements)

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“…We also revealed that oral administration of isohumulones to obese C57BL/6 mice for 2 weeks resulted in an increase in liver fatty acid oxidation and a normalization of in adipocyte hypertrophy, being likely due to coactivation of PPARa and PPARg by isohumulones. 10 In the present study, we confirmed that IHE activated PPARa, using an in vitro reporter assay. Quantitative RT-PCR analysis of the mRNAs from the liver of KK-A y mice indicated that the expression of ACO and MCAD, which are known to be regulated by PPARa and to be involved in b-oxidation in liver, 20 was increased by IHE supplementation.…”

Section: Discussionsupporting

confidence: 82%

“…8,9 We reported that isohumulones activate PPARs a and g using in vitro reporter assays, and that treatment of diabetic mice with isohumulones decreased their plasma glucose and lipid levels, improved their glucose tolerance, increased their liver fatty acid oxidation, and decreased the size of their hypertrophic adipocytes. 10 In this study, we examined the effects of IHE on obesity and insulin resistance in high-fat diet-fed rodents.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents

et al. 2005

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OBJECTIVE: Isomerized hop extract (IHE), which consists mainly of isohumulones and is required in the beer brewing process, was investigated for its effects on diet-induced obesity in two strains of mice. DESIGN: C57BL/6N and KK-A y mice were fed a standard or high-fat diet containing IHE and their body and tissue weights were measured at various time points. Oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were carried out in high-fat diet-fed C57BL/6N mice. The effects of IHE on intestinal lipid absorption were examined in Wistar rats using a plasma triacylglycerol assay after oral administration of a lipid emulsion. Fecal lipid levels were also measured in these animals after they were fed a high-fat diet containing IHE for 15 days. The effects of IHE on pancreatic lipase activity and the expression of genes involved in hepatic lipid metabolism were also examined using an in vitro assay and quantitative RT-PCR, respectively. RESULTS: Supplementation of high-fat-containing chow with IHE reduced body weight gain and improved glucose tolerance in our experimental mice. A reduction in body weight gain was also observed in C57BL/6N mice fed a standard diet containing IHE. Wistar rats fed a high-fat diet containing IHE showed reduced plasma triacylglycerol levels and an increase in their fecal lipid excretion. Similarly, their pancreatic lipase activity was inhibited and their elevation in plasma triacylglycerol levels seen after the oral administration of lipid emulsion was significantly suppressed. IHE-fed mice showed an increased expression in their lipid oxidation genes and a decreased expression in genes involved in triacylglycerol biosynthesis. CONCLUSION: The inhibition of intestinal dietary fat absorption may be the mechanism by which IHE induces its weightlowering effects in high-fat diet-fed mice. The modulatory effect of IHE on lipid metabolism may also, at least partly, be responsible for its beneficial effects on body weight gain. These results suggest that IHE may be helpful in humans in preventing diet-induced obesity and perhaps even metabolic syndrome, the latter of which is known to be associated with obesity.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents

et al. 2005

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“…1) suppress COX-2 expression and also activate PPARα and/or γ. 46,47) Similarly, essential oil components such as carvacrol and citral activate PPARs and suppress COX-2 expression. [48][49][50] These findings suggest that various food-derived components, including resveratrol, have similar effects on PPARs and COX-2.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Study on Resveratrol

Nakata

Takahashi

Inoue

2012

Biological & Pharmaceutical Bulletin

145

112

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Appropriate long-term drinking of red wine is associated with a reduced risk for lifestyle-related diseases such as cardiovascular disease and cancer, making resveratrol, a constituent of grapes and various other plants, an attractive compound to be studied. Historically, resveratrol has been identified as a phytoalexin, antioxidant, cyclooxygenase (COX) inhibitor, peroxisome proliferator-activated receptor (PPAR) activator, endothelial nitric oxide synthase (eNOS) inducer, silent mating type information regulation 2 homolog 1 (SIRT1) activator, and more. Despite scepticism concerning the biological availability of resveratrol, a growing body of in vivo evidence indicates that resveratrol has protective effects in several stress and disease models. Here, we provide a review of the studies on resveratrol, especially with respect to COX, PPAR, and eNOS activities, and discuss its potential for promoting human health.

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“…We also found that a 4-week intake of resveratrol led to upregulation of hepatic expression of SIRT1 in wild type, but not PPARα knockout mice (submitted). Polyphenolic compounds such as apigenin, chrysin (Liang et al, 1999;Woo et al, 2005), and humulon (Yamamoto et al, 2000) suppress COX-2 expression and activate PPARα and/or γ (Liang et al, 2001;Yajima et al, 2004). These findings suggest that various food-derived components have effects on PPARs and COX-2 that are comparable to those of resveratrol.…”

Section: Citral a Component Of Lemongrass Oilmentioning

confidence: 92%

Evaluation of Food-derived Functional Ingredients According to Activation of PPAR and Suppression of COX-2 Expression

Nakata

Takizawa

Takai

et al. 2013

FSTR

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The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor family. They are considered molecular targets for the prevention of lifestyle-related diseases and are involved in the control of cyclooxygenase (COX)-2 expression. COX-2, the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis, and its expression is partly controlled by PPAR. We have identified several natural chemicals, such as resveratrol, that activate PPARs and suppress COX-2 expression. In this review, we provide an evaluation of food-derived functional ingredients that target PPARs and COX-2.Keywords: PPAR, COX-2, resveratrol, essential oil, anti-lifestyle-related disease *To whom correspondence should be addressed. E-mail: inoue@cc.nara-wu.ac.jp IntroductionThe prevention of lifestyle-related diseases, such as cardiovascular disease, diabetes, and stroke, is of worldwide interest. Individuals tend to focus not only on drug therapy for prevention of these diseases, but also on the functionality of natural chemicals found in food and beverages, such as polyphenols and their polymers. A growing body of evidence supports the theory that polyphenolic compounds have activities that maintain health. Epidemiological studies have demonstrated that dietary polyphenol intake, e.g., red wine consumption, may improve endothelial function and reduce risk for cardiovascular diseases (Stoclet et al., 2004; Cordova et al., 2005;Opie et al., 2007). Although there have been numerous studies investigating food-derived functional components, the molecular mechanisms for their actions remain to be determined. We found that several natural food-derived components, such as resveratrol, activate peroxisome proliferator-activated receptors (PPARs) and suppress expression of cyclooxygenase (COX)-2. These two properties targeted specifically to PPARs and COX-2 will be important for evaluating food-derived functional components. This review discusses the effects of food-derived functional components on PPARs and COX-2, and evaluates novel functions of these compounds in relation to prevention of lifestyle-related diseases. Linkage Between PPAR and COX-2PPARs are members of a nuclear receptor family of ligand-dependent transcription factors (Mangelsdolf et al., 1995). The PPAR subfamily comprises three isotypes, PPARα, β/δ and γ, which play various roles in lipid and carbohydrate metabolism, cell proliferation and differentiation, and inflammation; they are considered molecular targets in the prevention of lifestyle-related diseases (Michalik et al., 2006;Sonoda et al., 2008). For example, PPARα agonists, such as fibrates and thiazolidine derivatives, are used to treat dyslipidemia and diabetes, respectively. Moreover, eicosapentaenoic acid, a natural ligand for PPARα, has been used as a hypolipidemic drug and has been reported to lower plasma and liver cholesterol levels in a PPARα-dependent manner (Sugiyama et al., 2008).PPARs are also invo...

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Isohumulones, Bitter Acids Derived from Hops, Activate Both Peroxisome Proliferator-activated Receptor α and γ and Reduce Insulin Resistance

Cited by 151 publications

References 37 publications

Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents

Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents

Recent Advances in the Study on Resveratrol

Evaluation of Food-derived Functional Ingredients According to Activation of PPAR and Suppression of COX-2 Expression

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