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| − | == Weblinks ==
| + | '''Titel''': Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice<BR> |
| − | [http://www.dr-michalzik.de/medizinische-studien/Chlorogens%C3%A4ure_zeigt_K%C3%B6rpergewicht_reduzierende_Eingenschaften_und_verbessert_den_Fettstoffwechsel_bei_M%C3%A4usen_mit_fettreicher_Di%C3%A4t Cholrogensäurestudie|target='_blank']]
| + | '''Orginaltitel''': Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice<BR> |
| | + | '''Erschienen in''': Elsevier (2010) Untertitel: Food and Chemical Toxicology <BR> |
| | | | |
| | + | '''Autoren''': |
| | + | • Ae-Sim Cho, |
| | + | • Seon-Min Jeon, |
| | + | • Myung-Joo Kim, |
| | + | • Jiyoung Yeo, |
| | + | • Kwon-Il Seo, |
| | + | • Myung-Sook Choi, |
| | + | • Mi-Kyung Lee |
| | + | • Ibrahim Akyazie, |
| | + | |
| | | | |
| − | Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism
| + | ==Abstract== |
| − | in high-fat diet-induced-obese mice
| + | |
| − | Ae-Sim Cho a , Seon-Min Jeon b , Myung-Joo Kim c , Jiyoung Yeo d , Kwon-Il Seo e , Myung-Sook Choi b,
| + | This study investigated the efficacy of chlorogenic acid on altering body fat in high-fat diet (37% calories |
| − | * ,
| + | from fat) induced-obese mice compared to caffeic acid. Caffeic acid or chlorogenic acid was supplemented |
| − | Mi-Kyung Lee e,
| + | with high-fat diet at 0.02% (wt/wt) dose. Both caffeic acid and chlorogenic acid significantly lowered |
| − | *
| + | body weight, visceral fat mass and plasma leptin and insulin levels compared to the high-fat control |
| − | a Department of Nutrition Education, Graduate School of Education, Sunchon National University, Suncheon 540-742, Republic of Korea
| + | group. They also lowered triglyceride (in plasma, liver and heart) and cholesterol (in plasma, adipose tissue |
| − | b Department of Food Science and Nutrition, Kyungpook National University, Daegu 702-701, Republic of Korea
| + | and heart) concentrations. Triglyceride content in adipose tissue was significantly lowered, whereas |
| − | c Department of Food Science and Nutrition, Daegu Polytechnic College, Daegu 706-022, Republic of Korea
| + | |
| − | d School of Oriental Medicine, Pusan National University, Busan 626-810, Republic of Korea
| + | |
| − | e Department of Food and Nutrition, Sunchon National University, Suncheon 540-742, Republic of Korea
| + | |
| − | a r t i c l e i n f o
| + | |
| − | Article history:
| + | |
| − | Received 5 September 2009
| + | |
| − | Accepted 5 January 2010
| + | |
| − | Keywords:
| + | |
| − | Chlorogenic acid
| + | |
| − | Caffeic acid
| + | |
| − | High-fat diet
| + | |
| − | Lipid metabolism
| + | |
| − | Obesity
| + | |
| − | a b s t r a c t
| + | |
| − | This study investigated the efficacy of chlorogenic acid on altering body fat in high-fat diet (37% calories | + | |
| − | from fat) induced-obese mice compared to caffeic acid. Caffeic acid or chlorogenic acid was supple- | + | |
| − | mented with high-fat diet at 0.02% (wt/wt) dose. Both caffeic acid and chlorogenic acid significantly low-
| + | |
| − | ered body weight, visceral fat mass and plasma leptin and insulin levels compared to the high-fat control
| + | |
| − | group. They also lowered triglyceride (in plasma, liver and heart) and cholesterol (in plasma, adipose tis- | + | |
| − | sue and heart) concentrations. Triglyceride content in adipose tissue was significantly lowered, whereas
| + | |
| | the plasma adiponectin level was elevated by chlorogenic acid supplementation compared to the high-fat | | the plasma adiponectin level was elevated by chlorogenic acid supplementation compared to the high-fat |
| − | control group. Body weight was significantly correlated with plasma leptin (r = 0.894, p < 0.01) and insu- | + | control group. Body weight was significantly correlated with plasma leptin (r = 0.894, p < 0.01) and insulin |
| − | lin (r = 0.496, p < 0.01) levels, respectively. Caffeic acid and chlorogenic acid significantly inhibited fatty
| + | (r = 0.496, p < 0.01) levels, respectively. Caffeic acid and chlorogenic acid significantly inhibited fatty |
| − | acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA:cholesterol acyltransferase activ- | + | acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA:cholesterol acyltransferase activities, |
| − | ities, while they increased fatty acid b-oxidation activity and peroxisome proliferator-activated receptors
| + | while they increased fatty acid b-oxidation activity and peroxisome proliferator-activated receptors |
| − | a expression in the liver compared to the high-fat group. These results suggest that caffeic acid and chlor- | + | a expression in the liver compared to the high-fat group. These results suggest that caffeic acid and chlorogenic |
| − | ogenic acid improve body weight, lipid metabolism and obesity-related hormones levels in high-fat fed
| + | acid improve body weight, lipid metabolism and obesity-related hormones levels in high-fat fed |
| | mice. Chlorogenic acid seemed to be more potent for body weight reduction and regulation of lipid | | mice. Chlorogenic acid seemed to be more potent for body weight reduction and regulation of lipid |
| | metabolism than caffeic acid. | | metabolism than caffeic acid. |
| − | ! 2010 Elsevier Ltd. All rights reserved.
| + | |
| − | 1. Introduction | + | ==1. Introduction== |
| − | Phenolic acids are secondary metabolites, which are commonly | + | Phenolic acids are secondary metabolites, which are commonly found in plants. Many epidemiological studies have found that the |
| − | found in plants. Many epidemiological studies have found that the | + | consumption of foods and drinks with high phenolic content is associated with the prevention of coronary disease, cancer and so |
| − | consumption of foods and drinks with high phenolic content is | + | on (Hertog et al., 1995; Scalbert and Williamson, 2000). Among these, hydroxycinnamic acids constitute a major class of phenolic |
| − | associated with the prevention of coronary disease, cancer and so | + | acids that are widely available in seeds, fruits and vegetables.The daily intake of hydroxycinnamic acid derivates may easily |
| − | on (Hertog et al., 1995; Scalbert and Williamson, 2000). Among | + | reach 0.5–1 g in humans (Radtke et al., 1998; Clifford, 1999). Previous |
| − | these, hydroxycinnamic acids constitute a major class of phenolic | + | studies revealed that hydroxycinnamic acids (q-coumaricacid, caffeic acid, ferulic acid) and their derivates efficiently improved |
| − | acids that are widely available in seeds, fruits and vegetables. | + | hypercholesterolemia and type 2 diabetes (Kim et al., 2003; Lee et al., 2003; Jung et al., 2006). In particular, caffeic acid |
| − | The daily intake of hydroxycinnamic acid derivates may easily | + | is one of the most abundant hydroxycinnamic acids in the human diet and may occur in esterified form with ether quinic acid or tartaric acid (Gonthier et al., 2006). Among the quinic acid conjugates, chlorogenic acid (5-O-caffeoylquinic acid, Fig. 1) is predominant in plants, fruits and vegetables such as coffee beans, apples, pears, tomatoes, blueberries, potatoes, peanuts and eggplants (Azuma |
| − | reach 0.5–1 g in humans (Radtke et al., 1998; Clifford, 1999). Pre- | + | |
| − | vious studies revealed that hydroxycinnamic acids (q-coumaric
| + | |
| − | acid, caffeic acid, ferulic acid) and their derivates efficiently im-
| + | |
| − | proved hypercholesterolemia and type 2 diabetes (Kim et al.,
| + | |
| − | 2003; Lee et al., 2003; Jung et al., 2006). In particular, caffeic acid | + | |
| − | is one of the most abundant hydroxycinnamic acids in the human | + | |
| − | diet and may occur in esterified form with ether quinic acid or tar- | + | |
| − | taric acid (Gonthier et al., 2006). Among the quinic acid conjugates,
| + | |
| − | chlorogenic acid (5-O-caffeoylquinic acid, Fig. 1) is predominant in | + | |
| − | plants, fruits and vegetables such as coffee beans, apples, pears, | + | |
| − | tomatoes, blueberries, potatoes, peanuts and eggplants (Azuma | + | |
| | et al., 2000). | | et al., 2000). |
| − | Chlorogenic acid inhibits carcinogenesis in the colon, liver, and | + | Chlorogenic acid inhibits carcinogenesis in the colon, liver, and tongue, and protects against oxidative stress in vivo (Mori et al., |
| − | tongue, and protects against oxidative stress in vivo (Mori et al., | + | 1986; Tanaka et al., 1993; Tsuchiya et al., 1996). Chlorogenic acid has been claimed to modulate the glucose-6-phosphatase involved in glucose metabolism (Hemmerle et al., 1997) and to reduce the risk cardiovascular disease by decreasing oxidation of low density lipoprotein (LDL)-cholesterol and total cholesterol (Nardini et al.,1995). More recently, Hsu et al. (2006) reported that chlorogenic acid inhibited preadipocyte population growth, which may provide a proposed mechanism for reducing obesity. Therefore, there is increasing interest in an anti-obesity effect of chlorogenic acid in vivo. In this study, the anti-obesity potential of chlorogenic acid was investigated using high-fat diet-induced-obese mice by comparing |
| − | 1986; Tanaka et al., 1993; Tsuchiya et al., 1996). Chlorogenic acid | + | it with that of caffeic acid.<BR> <BR> <BR> <BR> </BR> |
| − | has been claimed to modulate the glucose-6-phosphatase involved | + | |
| − | in glucose metabolism (Hemmerle et al., 1997) and to reduce the | + | |
| − | risk cardiovascular disease by decreasing oxidation of low density | + | |
| − | lipoprotein (LDL)-cholesterol and total cholesterol (Nardini et al., | + | |
| − | 1995). More recently, Hsu et al. (2006) reported that chlorogenic | + | |
| − | acid inhibited preadipocyte population growth, which may provide | + | ==Ergebnisse== |
| − | a proposed mechanism for reducing obesity. Therefore, there is | + | Curcumin verbesserte signifikant (p<0,05) die histopathologischen Parameter. Die Caspase-3 Aktivität war verringert und die Trypsin Aktivität erhöht. |
| − | 0278-6915/$ - see front matter ! 2010 Elsevier Ltd. All rights reserved.
| + | NF-κB wurde gehemmt und das "activator protein "(AP-1) wurde verringert. Stickoxid (NO) Spiegel wurden verringert. Chemokine, TNF-α, Interleukon 6 (IL-6) und mRNA Spiegel waren zeitweilig erniedrigt |
| − | doi:10.1016/j.fct.2010.01.003
| + | |
| − | * Corresponding authors. Addresses: Department of Food Science and Nutrition,
| + | ==Schlussfolgerung== |
| − | Kyungpook National University, 1370 Sankyuk-dong, Buk-gu, Daegu, 702-701,
| + | Curcumin verringerte eine reihe von proinflammtorischer Parameter. AP-1, NF-κB und die Trypsin-Aktivität wurden gehemmt. Die Spiegel von TNF-α, IL-6 iNOS und NO. Es konnte eine Verringerung der Gewebeverletzung im Rahmen einer akuten Pankreatitis festgestellt werden. Allerdings konnte keine Korrelation zwischen des Einflusses auf die Zytokine und des schützenden Effektes auf das Gewebe festgestellt werden. |
| − | Korea (M.-S. Choi); Department of Food and Nutrition, Sunchon National University,
| + | |
| − | 413 Jungangno, Suncheon, Jeonnam, 540-742, Republic of Korea (M.-K. Lee). Tel.:
| + | ==Weblinks== |
| − | +82 53 950 6232; fax: +82 53 950 6229 (M.-S. Choi), Tel.: +82 61 750 3656; fax: +82
| + | |
| − | 61 752 3657 (M.-K. Lee).
| + | [http://www.sciencedirect.com/science/article/pii/S1424390313004304 http://www.sciencedirect.com/science/article/pii/S1424390313004304 |target='_blank'] |
| − | E-mail addresses: mschoi@knu.ac.kr (M.-S. Choi), leemk@sunchon.ac.kr (M.-K.
| + | |
| − | Lee).
| + | |
| − | Food and Chemical Toxicology 48 (2010) 937–943
| + | |
| − | Contents lists available at ScienceDirect
| + | |
| − | Food and Chemical Toxicology
| + | |
| − | journal homepage: www.elsevier.com/locate/foodchemtoxincreasing interest in an anti-obesity effect of chlorogenic acid
| + | |
| − | in vivo. In this study, the anti-obesity potential of chlorogenic acid | + | |
| − | was investigated using high-fat diet-induced-obese mice by com- | + | |
| − | paring it with that of caffeic acid.
| + | |
| − | 2. Methods and materials
| + | |
| − | 2.1. Animals and diets
| + | |
| − | Thirty-two male ICR mice (4 weeks old) were obtained from Orient Inc. (Seoul,
| + | |
| − | Republic of Korea). The mice were all individually housed in polycarbonate cages at
| + | |
| − | 22 ± 2 "C on a 12 h light–dark cycle. All mice were fed pellets of commercial chow
| + | |
| − | for 1 week after arrival. The mice were randomly divided into four groups (n = 8),
| + | |
| − | and respectively fed a normal diet (5% corn oil, wt/wt), a high-fat diet containing
| + | |
| − | 37% calories from fat (21% beef tallow, wt/wt), a high-fat diet plus 0.02% caffeic acid
| + | |
| − | (0.2 g/kg diet, TCI Co., Ltd., Japan) and a high-fat diet plus 0.02% chlorogenic acid
| + | |
| − | (0.2 g/kg diet, TCI Co., Ltd., Japan). The composition of the experimental diet (Ta-
| + | |
| − | ble 1) was based on the AIN-76 semisynthetic diet (American Institute of Nutrition,
| + | |
| − | 1977, 1980). The mice had free access to food and water, and their food consump-
| + | |
| − | tion was measured daily while their weight gain was measured weekly.
| + | |
| − | At the end of the experimental period, the mice were anesthetized with ether
| + | |
| − | after withholding food for 12 h. Blood samples were taken from the inferior vena
| + | |
| − | cava to determine the plasma biomarkers. After collecting the blood, the liver, adi-
| + | |
| − | pose tissue and heart were removed, rinsed with a physiological saline solution and
| + | |
| − | immediately stored at ! 70 "C. The white adipose tissues (epididymal and perirenal)
| + | |
| − | were collected and then weighed immediately. All of the mice were treated in strict
| + | |
| − | accordance with the Sunchon National University guidelines for the care and use of
| + | |
| − | laboratory animals.
| + | |
| − | 2.2. Plasma leptin, insulin and adiponectin levels
| + | |
| − | The plasma leptin (R&D systme, USA), adiponectin (R&D systme, USA) and insu-
| + | |
| − | lin (Shibaygi Co., Ltd., Japan) levels were determined using a quantitative sandwich
| + | |
| − | enzyme immunoassay kit.
| + | |
| − | 2.3. Plasma and tissue lipids
| + | |
| − | The plasma concentrations of total cholesterol, HDL-cholesterol and triglyceride
| + | |
| − | (Asan Diagnostics, Seoul, Korea) were determined using an enzymatic method. The
| + | |
| − | plasma free fatty acid (FFA) concentrations were determined using an enzymatic
| + | |
| − | colorimetric method (Wako Chemicals, Richmond, VA). The hepatic, adipose tissue
| + | |
| − | and heart lipids were extracted using the procedure developed by Folch et al. (1957)
| + | |
| − | and the cholesterol and triglyceride concentrations were analyzed with the same
| + | |
| − | enzymatic kit as used in the plasma analysis.
| + | |
| − | 2.4. Preparation of samples
| + | |
| − | The enzyme source fractions in the liver were prepared according to the method
| + | |
| − | developed by Hulcher and Oleson (1973) with a slight modification. A 20% (w/v)
| + | |
| − | homogenate was prepared in a buffer containing 0.1 M triethanolamine, 0.02 M
| + | |
| − | EDTA and 2 mM dithiothreitol (pH 7.0). This homogenate was centrifuged at 600g
| + | |
| − | for 10 min to discard any cellular debris. The supernatant was then centrifuged at
| + | |
| − | 10,000g for 20 min and then again at 12,000g for 20 min at 4 "C to remove the mito-
| + | |
| − | chondrial pellet. Subsequently, the supernatant was ultracentrifuged twice at
| + | |
| − | 100,000g for 60 min at 4 "C to obtain the cytosolic supernatant. The mitochondrial
| + | |
| − | and microsomal pellets were then redissolved in 800 lL of a homogenization buffer,
| + | |
| − | and their protein content was determined by the method of Bradford (Bradford,
| + | |
| − | 1976) using bovine serum albumin (BSA) as the standard.
| + | |
| − | 2.5. Hepatic lipid-regulating enzyme activities
| + | |
| − | The fatty acid synthase (FAS) activity was determined by a spectrophotometric
| + | |
| − | assay. This assay is based on measuring the malonyl-CoA-dependent oxidation of
| + | |
| − | NADPH according to the methods by Nepokroeff et al. (1975) with a slight modifi-
| + | |
| − | cation. One unit of enzyme activity represented the oxidation of 1 nmol of NADPH
| + | |
| − | per minute at 37 "C. Fatty acid b-oxidation (b-oxidation) activity was measured
| + | |
| − | spectrophotometrically by monitoring the reduction of NAD to NADH in the pres-
| + | |
| − | ence of palmitoyl-CoA as described by Lazarow (1981) with a slight modification.
| + | |
| − | 3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase activity was determined in
| + | |
| − | the microsome with [ 14 C]-HMG-CoA as the substrate based on a modification of
| + | |
| − | the method of Shapiro et al. (1974). The activity was expressed as the synthesized
| + | |
| − | mevalonate pmol/min/mg protein. Acyl-CoA:cholesterol acyltransferase (ACAT)
| + | |
| − | activity was determined by the rate of incorporation of [ 14 C]-oleoyl CoA into choles-
| + | |
| − | terol ester fractions, as described by Erickson et al. (1980) and modified by Gillies
| + | |
| − | et al. (1986). The activity was expressed as synthesized cholesteryl oleate pmol/
| + | |
| − | min/mg protein.
| + | |
| − | 2.6. Western blot analysis
| + | |
| − | The liver was homogenized with a buffer containing 50 mM 4-(2-hydroxy-
| + | |
| − | ethyl)piperazine-1-ethanesulfonic acid (Hepes), 150 mM NaCl, 1 mM ethylenedi-
| + | |
| − | aminetetraacetic acid (EDTA), 2 mM ethylene glycol-bis(2-aminoethylether-
| + | |
| − | tetraacetic acid (EGTA), 50 mM NaF, 1% triton-X, 1 mM phenylmethylsulfonyl fluo-
| + | |
| − | ride, 25 lg/mL leupeptin and 2 lg/mL aprotinin. Lysates were centrifuged at 8550g
| + | |
| − | for 1 h at 4 "C. The supernatant protein content was determined following the
| + | |
| − | method established by Bradford (1976), using BSA as the standard. Equal amounts
| + | |
| − | of protein (30 lg per lane) were separated by 7% sodium dodecyl sulfate (SDS)–
| + | |
| − | polyacrylamide gel electrophoresis, transferred onto nitrocellulose membranes,
| + | |
| − | blocked BSA and incubated overnight with polyclonal rabbit anti-PPAR a (1:200)
| + | |
| − | (Santa Cruz Biotechnology, Inc., USA). After a washing procedure, the blots were
| + | |
| − | incubated with horseradish peroxidase-conjugated anti-rabbit secondary antibody
| + | |
| − | (Santa Cruz Biotechnology, Inc., USA) for 1 h at room temperature. The immunore- | + | |
| − | active bands were visualized with an enhanced chemiluminescence kit according to
| + | |
| − | the manufacture’s instructions (Santa Cruz Biotechnology, Inc., USA). The blots were
| + | |
| − | stripped by treating them two times for 30 min with 200 mM glycine, 0.1% SDS and
| + | |
| − | 1% Tween-20 followed, washed, again incubated overnight at 4 "C with b-actin anti-
| + | |
| − | body (1:1000) (Santa Cruz Biotechnology, Inc., USA) and the remaining procedures
| + | |
| − | as described above were followed. The b-actin was used for loading standardization.
| + | |
| − | 2.7. Statistical analysis
| + | |
| − | All data are presented as the mean ± S.E. The data were evaluated by a one-way
| + | |
| − | ANOVA SPSS program and by determining the differences between the means using
| + | |
| − | the Duncan’s multiple-range test. Correlation analyses utilized the Pearson’s coeffi-
| + | |
| − | cient. Values were considered statistically significant when p < 0.05.
| + | |
| − | 3. Results
| + | |
| − | 3.1. Body weight, food intake, energy intake and visceral fat weight
| + | |
| − | The final body weight of mice fed the high-fat diet was signifi-
| + | |
| − | cantly higher than that of mice fed the normal diet (Table 2). How-
| + | |
| − | Table 1
| + | |
| − | Composition of the experimental diets.
| + | |
| − | Component Normal %
| + | |
| − | (w/w)
| + | |
| − | HF control %
| + | |
| − | (w/w)
| + | |
| − | HF-caffeic
| + | |
| − | acid % (w/w)
| + | |
| − | HF-
| + | |
| − | chlorogenic
| + | |
| − | acid % (w/w)
| + | |
| − | Casein 20.0 20.0 20.0 20.0
| + | |
| − | Corn starch 50.0 34.0 33.98 33.98
| + | |
| − | Sucrose 15.0 15.0 15.0 15.0
| + | |
| − | Cellulose 5.0 5.0 5.0 5.0
| + | |
| − | Corn oil 5.0 – – –
| + | |
| − | Beef tallow – 21.0 21.0 21.0
| + | |
| − | AIN-mineral mixture a 3.5 3.5 3.5 3.5
| + | |
| − | AIN-vitamin mixture b 1.0 1.0 1.0 1.0
| + | |
| − | DL -Methionine 0.3 0.3 0.3 0.3
| + | |
| − | Choline bitartrate 0.2 0.2 0.2 0.2
| + | |
| − | Caffeic acid – – 0.02 –
| + | |
| − | Chlorogenic acid – – – 0.02
| + | |
| − | Total (%) 100 100 100 100
| + | |
| − | kcal/100 g diet 421.5 515.5 510 513.5
| + | |
| − | Calories from fat (%) 11.0 37.0 37.0 37.0
| + | |
| − | a Mineral mixture according to AIN-76.
| + | |
| − | b Vitamin mixture according to AIN-76.
| + | |
| − | Fig. 1. Chemical structures of caffeic acid and chlorogenic acid.
| + | |
| − | 938 A.-S. Cho et al. / Food and Chemical Toxicology 48 (2010) 937–943ever, the caffeic acid and its ester chlorogenic acid supplements
| + | |
| − | significantly reduced body weight compared to the high-fat control
| + | |
| − | group by 8% and 16%, respectively. Among the high-fat fed groups,
| + | |
| − | body weight gain was significantly lower in the chlorogenic acid
| + | |
| − | group compared to the high-fat control or caffeic acid supple-
| + | |
| − | mented group. Caffeic acid and chlorogenic acid did not affect food
| + | |
| − | intake and daily energy intake in high-fat feeding mice (Table 2).
| + | |
| − | Obesity with predominant visceral fat is associated with diabe-
| + | |
| − | tes mellitus, dyslipidemia and hypertension. As shown in Fig. 2,
| + | |
| − | visceral fat weight of mice fed high-fat diet for 8 weeks was signif-
| + | |
| − | icantly higher than the normal group. However, the epididymal
| + | |
| − | white adipose tissues weight was significantly lower in the caffeic
| + | |
| − | acid and chlorogenic acid groups as compared to the high-fat con-
| + | |
| − | trol group by 22% and 46%, respectively (Fig. 2). In particular, the
| + | |
| − | perirenal adipose tissue weight of the chlorogenic acid was only
| + | |
| − | 42% of the high-fat control value (Fig. 2).
| + | |
| − | 3.2. Plasma leptin, insulin and adiponectin levels
| + | |
| − | A high-energy diet generally increases adipose tissue mass and
| + | |
| − | leptin secretion, which induces leptin resistance, resulting in lipo-
| + | |
| − | toxicity (Torre-Villalvazo et al., 2008). To evaluate the effect of
| + | |
| − | chlorogenic acid on plasma insulin and adipokine levels, we deter-
| + | |
| − | mined the plasma leptin, insulin and adiponectin concentrations
| + | |
| − | using ELISA assay.
| + | |
| − | The high-fat control diet caused to increase the plasma leptin
| + | |
| − | and insulin levels significantly compared to the normal diet fed
| + | |
| − | mice, while it decreased the plasma adiponectin level. However,
| + | |
| − | both caffeic acid and chlorogenic acid supplemented groups were
| + | |
| − | lower in the plasma letpin and insulin levels compared to the
| + | |
| − | high-fat control group (Table 3). In this study, the leptin level
| + | |
| − | was positively correlated with the insulin level in plasma
| + | |
| − | (r = 0.594, p < 0.01). Body weight was positively correlated with
| + | |
| − | the plasma leptin level (r = 0.894, p < 0.01) and the insulin level
| + | |
| − | (r = 0.496, p < 0.01), respectively. Epididymal white adipose tissue
| + | |
| − | weight was positively correlated with the plasma leptin level
| + | |
| − | (r = 0.791, p < 0.01) and the insulin level (r = 0.462, p < 0.01) after
| + | |
| − | the 8-week experimental period (Fig. 3). When compared to the
| + | |
| − | high-fat control group, the plasma adiponectin concentration was
| + | |
| − | only significantly higher in the chlorogenic acid group (Table 3).
| + | |
| − | 3.3. Lipid contents in plasma, liver, adipose tissue and heart
| + | |
| − | Supplementation of caffeic acid and chlorogenic acid to a high-
| + | |
| − | fat diet significantly lowered the plasma triglyceride and total cho-
| + | |
| − | lesterol concentrations compared to the high-fat group. Plasma
| + | |
| − | free fatty acid concentration was significantly lowered by caffeic
| + | |
| − | acid and chlorogenic acid supplementation. In addition, the caffeic
| + | |
| − | acid and chlorogenic acid supplementation significantly increased
| + | |
| − | HDL-cholesterol to total cholesterol ratio compared to the high-
| + | |
| − | fat control group (Table 4).
| + | |
| − | Supplementation with caffeic acid and chlorogenic acid signifi-
| + | |
| − | cantly lowered the triglyceride concentrations in the liver and
| + | |
| − | heart compared to the high-fat control group (Fig. 4). Adipose tis-
| + | |
| − | sue triglyceride concentration was only decreased by chlorogenic
| + | |
| − | acid supplementation. The cholesterol concentrations of adipose
| + | |
| − | tissue and heart were significantly lower in the caffeic acid and
| + | |
| − | chlorogenic acid groups compared to the high-fat control group
| + | |
| − | (Fig. 4).
| + | |
| − | 3.4. Activities of hepatic lipid-regulating enzymes
| + | |
| − | To understand the mechanism involved in the effect of chloro-
| + | |
| − | genic acid on lipid metabolism, hepatic lipid-regulating enzymes
| + | |
| − | activities such as lipogenesis, fatty acid oxidation and cholesterol
| + | |
| − | synthesis were investigated.
| + | |
| − | The hepatic FAS, HMG-CoA reductase and ACAT activities were
| + | |
| − | significantly higher in the high-fat control group than in the nor-
| + | |
| − | mal group, whereas the b-oxidation activity was significantly low-
| + | |
| − | er (Table 5). The caffeic acid and chlorogenic acid lowered hepatic
| + | |
| − | FAS, HMG-CoA reductase and ACAT activities compared to the
| + | |
| − | high-fat control group, while they elevated fatty acid b-oxidation
| + | |
| − | activity. Thus, caffeic acid and chlorogenic acid inhibited fatty acid
| + | |
| − | and cholesterol synthesis and stimulated fatty acid oxidation in the
| + | |
| − | liver (Table 5).
| + | |
| − | Table 2
| + | |
| − | Effect of caffeic acid and chlorogenic acid supplementation on body weight, food intake and daily energy intake in high-fat diet-induced-obese mice. *
| + | |
| − | Initial body weight (g) Final body weight (g) Body weight gain (g) Food intake (g/day) Energy intake (kcal/day)
| + | |
| − | Normal 28.49 ± 0.38 42.28 ± 0.73 a 13.90 ± 0.91 ab 7.07 ± 0.30 29.83 ± 1.26 a
| + | |
| − | HF control 28.75 ± 0.42 47.47 ± 2.05 b 18.50 ± 1.32 c 6.58 ± 0.30 33.90 ± 0.38 b
| + | |
| − | HF-caffeic acid 28.42 ± 0.40 43.53 ± 1.05 a 15.45 ± 1.07 bc 6.32 ± 0.13 32.24 ± 0.46 b
| + | |
| − | HF-chlorogenic acid 28.53 ± 0.22 40.05 ± 1.26 a 11.79 ± 0.97 a 6.28 ± 0.08 32.20 ± 0.49 b
| + | |
| − | abc The means in the column not sharing a common letter are significantly different between groups (p < 0.05).
| + | |
| − | * Values are expressed as means ± S.E.
| + | |
| − | Fig. 2. Effect of caffeic acid and chlorogenic acid supplementation on visceral fat
| + | |
| − | weight in high-fat diet-induced-obese mice. Values are expressed as means ± S.E.
| + | |
| − | abc The means not sharing a common letter are significantly different between
| + | |
| − | groups (p < 0.05).
| + | |
| − | Table 3
| + | |
| − | Effect of caffeic acid and chlorogenic acid supplementation on plasma leptin, insulin
| + | |
| − | and adiponectin concentrations in high-fat diet-induced-obese mice. *
| + | |
| − | Leptin
| + | |
| − | (ng/mL)
| + | |
| − | Insulin
| + | |
| − | (ng/mL)
| + | |
| − | Adiponectin
| + | |
| − | (ug/mL)
| + | |
| − | Normal 3.32 ± 0.30 a 5.32 ± 0.21 a 7.41 ± 0.41 ab
| + | |
| − | HF control 5.58 ± 0.50 b 6.93 ± 0.25 b 3.92 ± 0.37 c
| + | |
| − | HF-caffeic acid 3.32 ± 0.34 a 5.21 ± 0.33 a 4.24 ± 0.49 c
| + | |
| − | HF-chlorogenic acid 2.52 ± 0.15 a 4.86 ± 0.45 a 6.02 ± 0.23 b
| + | |
| − | abc The means in the column not sharing a common letter are significantly different
| + | |
| − | between groups (p < 0.05).
| + | |
| − | * Values are expressed as means ± S.E.
| + | |
| − | A.-S. Cho et al. / Food and Chemical Toxicology 48 (2010) 937–943 9393.5. Expression of hepatic PPAR a
| + | |
| − | PPAR a is one of nuclear transcription factors that act as lipid
| + | |
| − | sensors and regulate lipid metabolism (Willson and Wahli,
| + | |
| − | 1997). Liver is the major target tissue of PPAR a, and its key
| + | |
| − | genes include the enzymes involved in the b-oxidation of fatty
| + | |
| − | acid (Chen et al., 2008). Therefore, we examined the hepatic
| + | |
| − | PPAR a expression by Western blotting. In comparison with
| + | |
| − | the high-fat control group, supplementation of caffeic acid and
| + | |
| − | chlorogenic acid stimulated the expression of PPAR a in the liver
| + | |
| − | (Fig. 5).
| + | |
| − | 4. Discussion
| + | |
| − | The role of chlorogenic acid in a diet-induced obesity model has
| + | |
| − | not yet been fully established. Therefore, the effect of chlorogenic
| + | |
| − | acid has been investigated on body weight, body fat distribution
| + | |
| − | and lipid metabolism in high-fat diet-induced-obese mice by com-
| + | |
| − | paring it with caffeic acid, which is an unesterified structure of
| + | |
| − | chlorogenic acid.
| + | |
| − | This study demonstrated that caffeic acid and its ester, chloro-
| + | |
| − | genic acid, significantly reduced body weight, by approximately
| + | |
| − | 8% and 16%, respectively, and epididymal adipose tissue weight,
| + | |
| − | Fig. 3. Effect of caffeic acid and chlorogenic acid supplementation on correlation between parameters in high-fat diet-induced-obese mice.
| + | |
| − | Table 4
| + | |
| − | Effect of caffeic acid and chlorogenic acid supplementation on plasma lipid contents in high-fat diet-induced-obese mice. *
| + | |
| − | Triglyceride (mmol/L) Free fatty acid (mmol/L) Total cholesterol (mmol/L) HDL-cholesterol (mmol/L) HTR A (%)
| + | |
| − | Normal 1.65 ± 0.12 b 0.40 ± 0.03 a 3.23 ± 0.31 a 1.76 ± 0.05 52.17 ± 1.72 ab
| + | |
| − | HF control 1.95 ± 0.26 c 0.52 ± 0.05 b 5.53 ± 0.47 b 1.82 ± 0.06 34.73 ± 3.08 c
| + | |
| − | HF-caffeic acid 1.22 ± 0.16 ab 0.33 ± 0.01 a 4.09 ± 0.28 a 1.90 ± 0.17 46.15 ± 1.92 b
| + | |
| − | HF-chlorogenic acid 0.91 ± 0.09 a 0.30 ± 0.04 a 3.42 ± 0.27 a 1.86 ± 0.18 53.73 ± 1.19 a
| + | |
| − | abc The means in the column not sharing a common letter are significantly different between groups (p < 0.05).
| + | |
| − | * Values are expressed as means ± S.E.
| + | |
| − | A HTR = HDL-cholesterol/total cholesterol " 100.
| + | |
| − | 940 A.-S. Cho et al. / Food and Chemical Toxicology 48 (2010) 937–943by approximately 22% and 46%, respectively, compared to the high-
| + | |
| − | fat control group without changing daily food or energy intake. Un-
| + | |
| − | der a normal diet feeding condition, the oral administration of
| + | |
| − | chlorogenic acid (30 and 60 mg/kg/day) for 14 days reduced the
| + | |
| − | hepatic triglyceride content but the amount of visceral fat was un-
| + | |
| − | changed (Shimoda et al., 2006). However, in this study, chlorogenic
| + | |
| − | acid significantly lowered the body weight gain and perirenal adi-
| + | |
| − | pose weight compared to the high-fat control group and caffeic
| + | |
| − | acid group. Thus, chlorogenic acid suppressed body weight gain
| + | |
| − | and lowered visceral fat mass more efficiently than caffeic acid in
| + | |
| − | high-fat diet fed mice.
| + | |
| − | Visceral adipose tissue releases a large amount of free fatty
| + | |
| − | acids (FFA) and hormones/cytokines in the portal vein that can
| + | |
| − | be delivered to the liver and interact with hepatocytes and various
| + | |
| − | immune cells (Lafontan and Girard, 2008). It was also observed
| + | |
| − | that both the body weight and epididymal adipose weight were
| + | |
| − | positively correlated with plasma leptin and insulin levels, respec-
| + | |
| − | tively. The plasma leptin and insulin levels were significantly
| + | |
| − | Fig. 4. Effect of caffeic acid and chlorogenic acid supplementation on lipid contents of liver (A and B), epididymal adipose tissue (C and D) and heart (E and F) in high-fat diet-
| + | |
| − | induced-obese mice. Values are expressed as means ± S.E. abc The means not sharing a common letter are significantly different between groups (p < 0.05).
| + | |
| − | Table 5
| + | |
| − | Effect of caffeic acid and chlorogenic acid supplementation on hepatic lipid-regulating enzyme activities in high-fat diet-induced-obese mice. *
| + | |
| − | Fatty acid synthase A (nmol/min/mg
| + | |
| − | protein)
| + | |
| − | Fatty acid b-oxidation (nmol/min/mg
| + | |
| − | protein)
| + | |
| − | HMG-CoA reductase (pmol/min/mg
| + | |
| − | protein)
| + | |
| − | ACAT (pmol/min/mg
| + | |
| − | protein)
| + | |
| − | Normal 2.09 ± 0.17 a 7.06 ± 0.49 a 220.64 ± 20.89 a 169.34 ± 8.91 a
| + | |
| − | HF control 3.62 ± 0.08 b 3.41 ± 0.54 c 462.57 ± 19.33 c 250.60 ± 10.58 c
| + | |
| − | HF-caffeic acid 2.01 ± 0.26 a 5.43 ± 0.65 b 352.43 ± 23.30 b 210.87 ± 16.39 b
| + | |
| − | HF-chlorogenic
| + | |
| − | acid
| + | |
| − | 1.57 ± 0.11 a 7.24 ± 0.47 a 348.05 ± 20.21 b 207.40 ± 6.70 b
| + | |
| − | abc The means in the column not sharing a common letter are significantly different between groups (p < 0.05).
| + | |
| − | * Values are expressed as means ± S.E.
| + | |
| − | A FAS, fatty acid synthase; b-oxidation, free fatty acid b-oxidation; HMG-CoA reductase, 3-hydroxy-3-methylglutaryl CoA reductase; ACAT, acyl-coenzyme A:cholesterol
| + | |
| − | acyltransferase.
| + | |
| − | A.-S. Cho et al. / Food and Chemical Toxicology 48 (2010) 937–943 941higher in the high-fat group than in the normal diet group; how-
| + | |
| − | ever, these hormone levels were significantly lowered by caffeic
| + | |
| − | acid and chlorogenic acid supplementation. These results showed
| + | |
| − | a significant positive correlation between leptin and insulin levels
| + | |
| − | in the plasma (r = 0.594, p < 0.01).
| + | |
| − | During the development of leptin resistance, there is an in-
| + | |
| − | creased release of FFA from adipose tissue to other tissues, mainly
| + | |
| − | to the liver (Torre-Villalvazo et al., 2008). As a result, hepatic ester-
| + | |
| − | ification of FFA to triglycerides leads to the formation of fatty liver
| + | |
| − | that is accelerated by an increased lipogenesis as a consequence of
| + | |
| − | hyperinsulinemia and decreased FFA oxidation (Torre-Villalvazo
| + | |
| − | et al., 2008). In this study, it was confirmed that high-fat feeding
| + | |
| − | for 8 weeks to mice induced a (Mathieu et al., 2008) decrease of
| + | |
| − | fatty acid oxidation in the liver. Several studies have pointed out
| + | |
| − | that the most common form of insulin resistance is associated with
| + | |
| − | an increased accumulation visceral fat (Slawik and Vidal-Puig,
| + | |
| − | 2006). Prevention of hyperinsulinemia may ameliorate metabolic
| + | |
| − | abnormalities that occur in the liver as a consequence of obesity
| + | |
| − | (Torre-Villalvazo et al., 2008). In particular, visceral fat depot was
| + | |
| − | associated with metabolic abnormalities contributing to the devel-
| + | |
| − | opment of cardiovascular disease (Mathieu et al., 2008). The lipo-
| + | |
| − | toxic theory states that the accumulation of lipid in target organs
| + | |
| − | such as skeletal muscle, kidney, pancreas and heart, may contrib-
| + | |
| − | ute to the development of obesity-related disorders (Slawik and Vi-
| + | |
| − | dal-Puig, 2006). Recently, it has been reported that chlorogenic
| + | |
| − | acid (5 mg/kg body weight, intravenously) improved glucose toler-
| + | |
| − | ance and decreased plasma and hepatic lipids without changing
| + | |
| − | triglyceride concentration in the adipose tissue of (fa/fa) Zucker
| + | |
| − | rats, which is an animal model for obese type 2 diabetes (de Sotillo
| + | |
| − | and Hadley, 2002). However, in this study, caffeic acid and chloro-
| + | |
| − | genic acid significantly lowered the plasma FFA, triglyceride and
| + | |
| − | total cholesterol concentrations as well as lipid contents of tissues
| + | |
| − | such as liver, epididymal adipose tissue and heart.
| + | |
| − | This study showed that caffeic acid and chlorogenic acid in-
| + | |
| − | creased the expression of PPAR a with a simultaneous increase in
| + | |
| − | fatty acid b-oxidation in the liver compared to the high-fat control
| + | |
| − | group. In particular, chlorogenic acid normalized the activity of he-
| + | |
| − | patic fatty acid b-oxidation in diet-induced-obese mice to similar
| + | |
| − | to values of a normal diet fed group. In some preclinical studies,
| + | |
| − | more potent and selective PPAR a agonists have been shown to
| + | |
| − | prevent the development of diabetes/insulin resistance in rodent
| + | |
| − | models of diabetes by reducing adiposity, improving peripheral
| + | |
| − | insulin action, and exerting beneficial effects on pancreatic b-cells
| + | |
| − | (Guerre-Millo et al., 2000; Kim et al., 2003; Bergeron et al., 2006).
| + | |
| − | Previous research suggested that adiponectin increased fatty acid
| + | |
| − | combustion and energy consumption via PPAR a activation at least
| + | |
| − | in part, which led to decreased triglyceride content in the liver and
| + | |
| − | skeletal muscle and thus coordinately increased in vivo insulin sen-
| + | |
| − | sitivity (Kadowaki and Yamauchi, 2005). Plasma adiponectin level
| + | |
| − | has been reported to be significantly reduced in obese/diabetic
| + | |
| − | mice and humans (Yamauchi et al., 2001; Arita et al., 1999) and
| + | |
| − | to be decreased in patients with cardiovascular disease (Kumada
| + | |
| − | et al., 2003), hypertension (Ouchi et al., 2003), or metabolic syn-
| + | |
| − | drome (Trujillo and Scherer, 2005). Although both chlorogenic acid
| + | |
| − | and caffeic acid improved adiponectin to leptin ratio in diet-in-
| + | |
| − | duced-obese mice, only chlorogenic acid significantly elevated
| + | |
| − | plasma adiponectin concentration compared to the high-fat con-
| + | |
| − | trol group and caffeic acid group. Moreover, chlorogenic acid
| + | |
| − | seems to be a more potential stimulator of hepatic fatty acid b-oxi-
| + | |
| − | dation than caffeic acid. Furthermore, we showed that caffeic acid
| + | |
| − | and chlorogenic acid also efficiently inhibited fatty acid and cho-
| + | |
| − | lesterol biosynthesis as evidenced by suppressing the activities of
| + | |
| − | fatty acid synthase, HMG-CoA reductase and ACAT in the liver.
| + | |
| − | In conclusion, chlorogenic acid and caffeic acid exhibited a po-
| + | |
| − | tential anti-obesity effect in high-fat diet-induced mice, which
| + | |
| − | may be mediated by altering plasma adipokine level and body fat
| + | |
| − | distribution and down-regulating fatty acid and cholesterol bio-
| + | |
| − | synthesis, whereas up-regulating fatty acid oxidation and PPAR a
| + | |
| − | expression in the liver. Chlorogenic acid seemed to be more potent
| + | |
| − | and efficacious anti-obesity agent in diet-induced-obese mice than
| + | |
| − | caffeic acid. Although, more studies are needed to support this
| + | |
| − | promising mechanism, this research might provide implication in
| + | |
| − | human anti-obesity effect.
| + | |
| − | Conflict of Interest
| + | |
| − | The authors declare that there are no conflicts of interest.
| + | |
| − | Acknowledgement
| + | |
| − | This work was supported by the Science Research Center (SRC)
| + | |
| − | program of Korea Science and Engineering Foundation (KOSEF, No.
| + | |
| − | 2009-0063409).
| + | |
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This study investigated the efficacy of chlorogenic acid on altering body fat in high-fat diet (37% calories
from fat) induced-obese mice compared to caffeic acid. Caffeic acid or chlorogenic acid was supplemented
with high-fat diet at 0.02% (wt/wt) dose. Both caffeic acid and chlorogenic acid significantly lowered
body weight, visceral fat mass and plasma leptin and insulin levels compared to the high-fat control
group. They also lowered triglyceride (in plasma, liver and heart) and cholesterol (in plasma, adipose tissue
and heart) concentrations. Triglyceride content in adipose tissue was significantly lowered, whereas
the plasma adiponectin level was elevated by chlorogenic acid supplementation compared to the high-fat
control group. Body weight was significantly correlated with plasma leptin (r = 0.894, p < 0.01) and insulin
(r = 0.496, p < 0.01) levels, respectively. Caffeic acid and chlorogenic acid significantly inhibited fatty
acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA:cholesterol acyltransferase activities,
while they increased fatty acid b-oxidation activity and peroxisome proliferator-activated receptors
a expression in the liver compared to the high-fat group. These results suggest that caffeic acid and chlorogenic
acid improve body weight, lipid metabolism and obesity-related hormones levels in high-fat fed
mice. Chlorogenic acid seemed to be more potent for body weight reduction and regulation of lipid
metabolism than caffeic acid.
Phenolic acids are secondary metabolites, which are commonly found in plants. Many epidemiological studies have found that the
consumption of foods and drinks with high phenolic content is associated with the prevention of coronary disease, cancer and so
on (Hertog et al., 1995; Scalbert and Williamson, 2000). Among these, hydroxycinnamic acids constitute a major class of phenolic
acids that are widely available in seeds, fruits and vegetables.The daily intake of hydroxycinnamic acid derivates may easily
reach 0.5–1 g in humans (Radtke et al., 1998; Clifford, 1999). Previous
studies revealed that hydroxycinnamic acids (q-coumaricacid, caffeic acid, ferulic acid) and their derivates efficiently improved
hypercholesterolemia and type 2 diabetes (Kim et al., 2003; Lee et al., 2003; Jung et al., 2006). In particular, caffeic acid
is one of the most abundant hydroxycinnamic acids in the human diet and may occur in esterified form with ether quinic acid or tartaric acid (Gonthier et al., 2006). Among the quinic acid conjugates, chlorogenic acid (5-O-caffeoylquinic acid, Fig. 1) is predominant in plants, fruits and vegetables such as coffee beans, apples, pears, tomatoes, blueberries, potatoes, peanuts and eggplants (Azuma
et al., 2000).
Chlorogenic acid inhibits carcinogenesis in the colon, liver, and tongue, and protects against oxidative stress in vivo (Mori et al.,
1986; Tanaka et al., 1993; Tsuchiya et al., 1996). Chlorogenic acid has been claimed to modulate the glucose-6-phosphatase involved in glucose metabolism (Hemmerle et al., 1997) and to reduce the risk cardiovascular disease by decreasing oxidation of low density lipoprotein (LDL)-cholesterol and total cholesterol (Nardini et al.,1995). More recently, Hsu et al. (2006) reported that chlorogenic acid inhibited preadipocyte population growth, which may provide a proposed mechanism for reducing obesity. Therefore, there is increasing interest in an anti-obesity effect of chlorogenic acid in vivo. In this study, the anti-obesity potential of chlorogenic acid was investigated using high-fat diet-induced-obese mice by comparing
it with that of caffeic acid.
</BR>
Curcumin verbesserte signifikant (p<0,05) die histopathologischen Parameter. Die Caspase-3 Aktivität war verringert und die Trypsin Aktivität erhöht.
NF-κB wurde gehemmt und das "activator protein "(AP-1) wurde verringert. Stickoxid (NO) Spiegel wurden verringert. Chemokine, TNF-α, Interleukon 6 (IL-6) und mRNA Spiegel waren zeitweilig erniedrigt
Curcumin verringerte eine reihe von proinflammtorischer Parameter. AP-1, NF-κB und die Trypsin-Aktivität wurden gehemmt. Die Spiegel von TNF-α, IL-6 iNOS und NO. Es konnte eine Verringerung der Gewebeverletzung im Rahmen einer akuten Pankreatitis festgestellt werden. Allerdings konnte keine Korrelation zwischen des Einflusses auf die Zytokine und des schützenden Effektes auf das Gewebe festgestellt werden.
