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© 2007 American Society for Nutrition J. Nutr. 137:2629-2634, December 2007

Biochemical, Molecular, and Genetic Mechanisms

Dietary Fish Oil Upregulates Intestinal Lipid Metabolism and Reduces Body Weight Gain in C57BL/6J Mice1,2

Takuya Mori, Hidehiko Kondo*, Tadashi Hase, Ichiro Tokimitsu and Takatoshi Murase

Biological Science Laboratories, Kao Corporation, Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan

* To whom correspondence should be addressed. E-mail: kondo.hidehiko{at}kao.co.jp.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Fish oils (FO) rich in (n-3) PUFA exert hypolipidemic and antiobesity effects in association with modulated hepatic lipid metabolism. We recently demonstrated the possible involvement of intestinal lipid metabolism in the development of obesity. In this study, we examined the effect of FO ingestion on intestinal lipid metabolism in relation to obesity. When diet-induced obesity-prone C57BL/6J mice were fed an 8% FO, high-fat (30%) diet for 5 mo, body weight gain was significantly reduced compared with mice fed a 30% triacylglycerol (TG) diet without FO. In addition to modulating messenger RNA (mRNA) levels in the liver, FO ingestion for 2 wk affected the intestinal mRNA levels of lipid metabolism-related genes; those of carnitine palmitoyltransferase 1a, cytochrome P450 4A10, and malic enzyme were significantly higher in mice fed the 8% FO diet compared with mice fed the 30% TG diet. Northern blot analysis revealed that the expression levels of most lipid metabolism-related genes in the small intestine of mice fed the 8% FO diet were comparable to those in the liver. Furthermore, reflecting the difference at the mRNA level, FO ingestion affected lipid metabolism-related enzyme activity; fatty acid ß-oxidation, {omega}-oxidation, and malic enzyme activities in the small intestine of mice fed the 8% FO diet were 1.2-, 1.6-, and 1.7-fold those in mice fed the 30% TG diet, respectively. These findings suggest that an upregulation of intestinal lipid metabolism is associated with the antiobesity effect of FO.


   Introduction
TOP
 ABSTRACT
 Introduction
Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Fish oils (FO),3 which contain (n-3) PUFA such as eicosapentaenoic acid and docosahexaenoic acid (DHA), have hypolipidemic effects. FO treatment efficiently lowers blood lipids in patients with hypertriglyceridemia (1,2). In rodents, FO feeding prevents abdominal fat accumulation compared with the ingestion of other types of dietary oils (3–5).

(n-3) PUFA reduce mRNA expression of the genes coding for lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase {alpha} (ACACA) in liver or hepatic cells (6–9). In addition, (n-3) PUFA increase transcription of the regulatory molecules of fatty acid oxidation, such as acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (ACADM), and uncoupling protein 2 (UCP2), via activation of PPAR in the liver (10–12). Thus, fatty acid synthesis and ß-oxidation in the liver are suggested to be important factors for the improvement in lipid metabolism by (n-3) PUFA.

On the other hand, the small intestine also expresses ß-oxidation-related enzymes such as ACOX1 and ACADM at levels comparable to those in the liver (13,14), although the primary function of the small intestine as it relates to lipid metabolism is the resynthesis of triacylglycerol (TG) and the secretion of TG as chylomicrons. We recently demonstrated that ingestion of a high-fat diet induces the expression of fatty acid catabolism-related genes and that the basal and upregulated expression levels were higher in obesity-resistant A/J mice compared with obesity-prone C57BL/6J mice, suggesting that fatty acid catabolism in the small intestine is associated with the development of obesity (15).

As described above, the beneficial effects related to lipid metabolism of (n-3) PUFA are attributed to the modulation of hepatic lipid metabolism. Intestinal lipid metabolism, however, might also be involved in the beneficial effects of (n-3) PUFA. Therefore, to clarify the relationship between the regulation of intestinal lipid metabolism and the antiobesity effect of (n-3) PUFA, we examined the effect of FO ingestion on the mRNA expression of lipid metabolism-related genes and lipid metabolism-related enzyme activities in the small intestine of diet-induced obesity-prone C57BL/6J mice.


   Materials and Methods
TOP
 ABSTRACT
 Introduction
 Materials and Methods
Results
 Discussion
 LITERATURE CITED
 
    Mice and diets. Male C57BL/6J mice were obtained from Clea Japan at 6 wk of age and maintained at 23 ± 2°C under a 12-h-light/dark cycle (lights on from 0700 to 1900). The mice were fed a laboratory diet (CE-2; Clea Japan) for 1 wk to stabilize the metabolic conditions.

FO was purchased from Japan Chemical Feed (DHA46G). A mixture of safflower, rapeseed, and perilla oil was used as the standard TG oil (the fatty acid compositions of these oils are shown in Table 1).


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  		TABLE 1 Fatty acid compositions of standard TG1 oil and FO2

 
In Expt. 1, 40 mice were randomly divided into 5 groups (8 mice per group) and consumed ad libitum water and 1 of 5 synthetic diets containing 5% (by weight) TG oil (5% TG), 30% TG oil (30% TG), 28% TG oil plus 2% FO (2% FO), 26% TG oil plus 4% FO (4% FO), or 22% TG oil plus 8% FO (8% FO) (Table 2). The mice were housed at 4 per cage and fed the experimental diets for 5 mo. Body weight, white adipose tissue (WAT) mass, liver weight, blood analytes, and liver TG concentration were compared among the groups. In Expt. 2, 30 mice were randomly divided into 3 groups (10 mice per group) and allowed ad libitum access to water and 1 of 3 synthetic diets: 5% TG diet, 30% TG diet, or 8% FO diet (Table 2). The mice were housed at 5 per cage and fed the experimental diets for 2 wk. We used a dome-type cover on the feeding dish (Roden CAFE; Oriental Yeast) to avoid scattering of the powdered diet in the cage. Messenger RNA (mRNA) expressions and enzyme activities were compared among groups. The study was approved by the Animal Care Committee of Kao Tochigi Institute.


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  		TABLE 2 Composition of the experimental diets

 
Food intake was measured on a per-cage basis throughout the study every 2 or 3 d. Food intake (g·mouse–1·d–1) was determined by subtracting the remaining food weight from the initial food weight of the previous feeding day and dividing by the number of mice housed in the cage. The energy intake (kJ·mouse–1·d–1) was calculated from the food intake and the macronutrient composition of each diet.

    Blood analytes. On the final day of the experiment, mice were anesthetized by diethyl ether and blood was collected from fed mice via the postcaval vein. Plasma TG, total cholesterol, and glucose concentrations were measured using enzyme assay kits L-type Wako TG-H, L-type Wako CHO-H, and L-type Wako Glu2 (Wako), respectively.

    Liver TG. Mice were killed by bleeding from the inferior vena cava under diethyl ether anesthesia after blood collection and a portion of the liver was frozen in liquid nitrogen and maintained at –80°C until assayed. Total lipid was extracted from the liver using Folch's method (16). The extracted samples were dried under nitrogen gas, resolved in 2-propanol containing 10% Triton X-100 (wt:wt), and subjected to measurement of the lipid components. TG concentrations were determined using enzyme assay kit L-type Wako TG-H.

    Quantitative RT-PCR. Isolation of total RNA, production of cDNA, and real-time PCR were performed according to the method described previously (15). Primers (listed in Supplemental Table 1) were used for quantitative RT-PCR analysis. For quantitative precision, the same amount of total RNA was consistently used for each expression analysis and the expression amount of each gene was normalized by the expression of the housekeeping gene, ribosomal protein, large, P0.

    Northern blots. Northern blot analysis was performed according to the method described previously (17) with minor modification. The RNA samples from each tissue of 10 mice were pooled and used for northern blot analysis. Ten micrograms of total RNA was used for the analysis. Blotted membranes were hybridized with 32P-labeled cDNA probes at 68°C for 2 h using QuikHyb (Stratagene). Membranes were washed in 2x SSC-0.1% SDS at 68°C and in 0.1x SSC-0.1% SDS at 68°C. Each cDNA probe was prepared by RT-PCR using first-strand cDNA from mouse intestinal total RNA and primers (listed in Supplemental Table 1). The integrities of the cDNA probes were confirmed by direct sequencing of the gel-purified PCR products.

    Enzyme activities. Mice were food deprived for 3 h before dissection to minimize lipid contamination of the mucosal samples. The intestinal mucosa was scraped from the mouse intestine (0–15 cm from the pylorus) and homogenized on ice with 8 volumes (w:v) of 250 mmol/L sucrose buffer containing 0.1 mmol/L EDTA and 2 mmol/L HEPES (pH 7.3). Subcellular fractionation was performed according to the methods described by de Duve et al. (18). After centrifugation of the homogenate of the intestinal mucosa at 600 x g; 10 min, the supernatant was centrifuged at 12,500 x g; 20 min. The resultant precipitate containing mitochondria was resuspended in sucrose buffer and used for the measurement of ß-oxidation activity as the mitochondrial fraction. The supernatant was centrifuged at 100,000 x g; 30 min and the resulting supernatant was used for the measurement of malic enzyme (ME) activity in the cytosolic fraction. The precipitate was used for the measurement of {omega}-oxidation activity in the microsomal fraction. Protein concentrations were determined using a Micro BCA protein assay kit (Pierce). We measured ß-oxidation activity according to a method described previously (15) and the {omega}-oxidation activity according to the method described by Giera et al. (19), with minor modifications. The reaction mixture contained 50 mmol/L Tris-HCl (pH 7.5), 2.4 mmol/L NADPH, 20 mmol/L lauric acid containing 100 µmol/L [1-14C] lauric acid (0.5 mCi/L), and the microsomal fraction containing 100 µg protein in a final volume of 1 mL. The reaction was performed at 37°C for 15 min and terminated by adding 375 µL 10% sulfuric acid and 250 µL methanol. The reacted buffer was extracted 3 times with 1.5 mL n-hexane to remove residual radiolabeled lauric acid. The radioactivity of the aqueous phase was measured using a liquid scintillation counter.

We measured the NADP+-dependent cytosolic ME activity spectrophotometrically with a UV-2550 by observing the appearance of NADPH at 340 nm at 30°C according to the method described previously (15).

    Statistical analysis. All values are presented as means ± SD. We first tested the data for homogeneity of variance with Bartlett's test. When the variances were equal, the data were analyzed by 1-factor factorial ANOVA and then differences between individual group means were analyzed using the Tukey-Kramer test. If variances were unequal, we used the Steel-Dwass test [epididymal WAT weight, plasma TG, and glucose concentration, mRNA expression levels of Acca1b and Ucp2 in the liver, mRNA expression levels of carnitine palmitoyltransferase 1a (Cpt1a) and cytochrome P450 4A (Cyp4a10) in the small intestine]. The Tukey-Kramer test was performed using StatView 5.0 software (SAS Institute) and the Steel-Dwass test was performed using R (version 2.5.1; R Foundation for Statistical Computing). Significance was defined as a P-value of < 0.05.


   Results
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
Discussion
 LITERATURE CITED
 
    Body weight gain and fat accumulation in WAT and liver. In Expt. 1, the body weight gain, perirenal and retroperitoneal WAT weights, liver weight, plasma total cholesterol and liver TG concentrations of mice fed the 30% TG diet for 5 mo were significantly higher than those of mice fed the 5% TG diet or the 8% FO diet (Table 3). These values in mice fed 2 or 4% FO were intermediate. Epididymal WAT weight, plasma TG and glucose did not differ significantly among groups.


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  		TABLE 3 Body weight, food intake, liver and adipose tissue weights, and plasma glucose and lipids in C57BL/6J mice fed 5 or 30% TG or 2, 4, or 8% FO diets for 5 mo (Expt. 1)1

 
    Expression of fatty acid metabolism-related genes in the liver and small intestine. In Expt. 2, mRNA expression of Acox1, a fatty acid catabolism-related gene, in the liver of mice fed the 30% TG diet for 2 wk were slightly but significantly than that in mice fed the 5% TG diet; mRNA expression of other fatty acid catabolism-related genes, Acadm and Acca1b, did not differ between these groups. (Fig. 1A). The expressions of these 3 fatty acid catabolism-related genes in the liver of mice fed the 8% FO diet were significantly greater than those in mice fed the 5 or 30% TG diet. The mRNA expression level of Ucp2, a potential regulator of energy metabolism (20), was higher in mice fed the 8% FO diet and in mice fed the 30% TG diet than in those fed the 5% TG diet. The mRNA expression of fatty acid synthesis-related genes (Fasn and Acaca) in mice fed the 30% TG diet were significantly higher than those in mice fed the 5% TG diet and that of Fasn was lower in mice fed the 8% FO diet than in those fed the 30% TG diet.


Figure 1
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  		FIGURE 1  Expression of genes associated with fatty acid metabolism in the liver (A) and small intestine (B) of C57BL/6J mice fed 5, 30, or 8% FO diets for 2 wk (Expt. 2). The amount of mRNA was normalized to that of ribosomal protein, large, P0 mRNA and expressed relative to the 5% TG diet group. Values are means ± SD, n = 10. Means without common letter differ, P < 0.05.

 
In the small intestine, mRNA expression of some lipid metabolism-related genes, including Cpt1a, Acca1b, NADP+-dependent cytosolic malic enzyme (Mod1), acyl-CoA thioesterase (Acot2), and Cyp4a10, were significantly higher in mice fed the 30% TG diet than in mice fed the 5% TG diet. The mRNA expressions of these genes were even higher in mice fed the 8% FO diet compared with mice fed the 30% TG diet (Fig. 1B). Expressions of other lipid metabolism-related genes, pyruvate dehydrogenase kinase 4, and 3-hydroxy-3-methylglutaryl-CoA synthase 2, were also significantly higher in mice fed the 8% FO diet than in mice fed the 30% TG diet. The mRNA expressions of Acox1, Acadm, and Ucp2 did not differ in the 3 experimental diet groups (data not shown).

    Comparison of mRNA expression in the small intestine and liver. Northern blot analysis revealed that expression of Acox1 and pyruvate dehydrogenase kinase 4 in the small intestine was comparable to that in the liver of mice fed the same diet (Fig. 2). On the other hand, there was little expression of Acaa1b, Mod1, Acot2, and Cyp4a10 in the small intestine of mice fed the 5% TG diet, whereas these genes were highly expressed in the liver of the mice. Mod1 and Acot2 were highly expressed in the small intestine of mice fed the 30% TG and 8% FO diets and the expression levels in the small intestine of these mice were comparable to those in the liver. The mRNA expression levels of Fasn and Acaca in the small intestine were low and lower in mice fed the 8% FO diet than in mice fed the 30% TG diet, findings similar to those in the liver.


Figure 2
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  		FIGURE 2  Northern blot analysis of lipid metabolism-related genes in the small intestine and liver of C57BL/6 mice fed 5, 30, or 8% FO diets for 2 wk (Expt. 2). The RNA samples from 10 mice were pooled and subjected to Northern blot analysis as described in "Materials and Methods."

 
    Lipid metabolism-related enzyme activities. ß-Oxidation activity in the liver was higher in mice fed the 30% TG diet than in those fed the 5% TG diet (Table 4). The activity was even higher in mice fed the 8% FO diet was even higher: 1.8-fold that of mice fed the 30% TG diet. Similar to the liver, ß-oxidation activity in the small intestine also was significantly higher in mice fed the 30% TG diet than in mice fed the 5% TG diet (Table 4). In mice fed the 8% FO diet, the activity was 1.2-fold that in mice fed the 30% TG diet and 2.1-fold that in mice fed the 5% TG diet.


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  		TABLE 4 Enzyme activities in the liver and small intestine of C57BL6/J mice fed 5 or 30% TG or 8% FO diets for 2 wk (Expt. 2)1

 
In addition, {omega}-oxidation activity in the small intestine was significantly greater in mice fed the 30% TG diet than in mice fed the 5% TG diet and the activity was even higher in mice fed the 8% FO diet (Table 4), consistent with the expression pattern of the Cyp4a10 gene. The intestinal {omega}-oxidation activity in mice fed the 8% FO diet was 1.6-fold that in mice fed the 30% TG diet and 6.2-fold that in mice fed the 5% TG diet.

Although the cytosolic ME activity in the small intestine did not differ between mice fed the 5% and 30% TG diets, it was significantly higher than in mice fed the 8% FO diet, reflecting the expression pattern of the Mod1 gene. The ME activity in mice fed the 8% FO diet was 2.1-fold that in mice fed the 5% diet and 1.7-fold that in mice fed the 30% TG diet (Table 4).


   Discussion
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
LITERATURE CITED
 
In this study, FO ingestion stimulated lipid metabolism in the small intestine of diet-induced obesity-prone C57BL/6J mice in which FO ingestion exerted an antiobesity effect. FO ingestion upregulated lipid metabolism-related genes, including Cpt1a, Mod1, and Cyp4a10, in the small intestine. Furthermore, FO ingestion induced enzyme activities related to fatty acid catabolism and the upregulated fatty acid ß-oxidation activity in the small intestine was comparable to that in the liver. These findings suggest an association between the upregulation of intestinal fatty acid catabolism and the antiobesity effect of FO.

In our experiments, ingestion of 8% FO reduced hepatic fat accumulation and body weight gain in mice fed high-fat diets. Consistent with previous reports (6–12), FO ingestion modulated the expression of fatty acid metabolism-related genes in the liver; gene expression of enzymes involved in fatty acid catabolism, Acox1 and Acadm, was greater in mice fed 8% FO than that in mice fed 30% TG, whereas gene expression of the enzyme involved in fatty acid synthesis, Fasn, was less in mice fed 8% FO. The induction of hepatic fatty acid-metabolizing enzymes, including peroxisomal and mitochondrial ß-oxidation enzymes, and microsomal {omega}-oxidation enzymes creates an increased capacity for fatty acid catabolism. The increased oxidation of fatty acids in the liver is thought to drain fatty acids from the body, reduce VLDL formation, and exert antiobesity effects (21). Several studies demonstrated that the upregulation of fatty acid catabolism by PPAR{alpha} agonists in the liver and brown adipose tissue is associated with reduced fat accumulation in rodent models of high-fat diet-induced or genetic insulin resistance (9,22,23). In this study, FO ingestion increased ß-oxidation and {omega}-oxidation activities in the intestine and liver. The small intestine is one of the largest organs expressing ß-oxidation-related enzymes (13,14). The expression of fatty acid catabolism-related genes is predominantly upregulated in obesity-resistant A/J mice by high-fat diets compared with obesity-prone C57BL/6J mice, suggesting that the lipid metabolism capacity in the small intestine is associated with the development of obesity (15). Considering that the surface area of the villus mucosa of the small intestine is quite large, the activation of intestinal fatty acid catabolism by FO ingestion might also result in a substantial reduction in the amount of TG entering the bloodstream and subsequently reduce fat accumulation and body weight gain.

FO ingestion upregulated mRNA expression of fatty acid catabolism-related enzymes such as Cpt1a, Mod1, 3-hydroxy-3-methylglutaryl-CoA synthase 2, and Cyp4a10 in the small intestine. The expression of these genes is upregulated by hypolipidemic fibrate, a PPAR{alpha} activator, and most of the genes have a PPAR response element in their promoter region (24–27). PPAR is a ligand-activated transcriptional factor belonging to the nuclear hormone receptor superfamily, which is considered to have an important role in the control of lipid metabolism (28–32). PPAR{alpha} is abundantly expressed in the small intestine and liver (33,34). In addition, FFA function as intrinsic ligands for PPAR (32). Keller et al. (35) investigated the effects of various fatty acids on PPAR{alpha} transcriptional activity and showed that PPAR{alpha} activation is increased by (n-3) and (n-6) PUFA. Lin et al. (36) also demonstrated that long-chain fatty acids including (n-3) PUFA interact with PPAR{alpha} at physiologic concentrations. Therefore, the increased expression of these lipid metabolism-related genes in response to FO ingestion might be explained by the activation of PPAR{alpha} by the (n-3) PUFA in FO. On the other hand, previous studies report that FFA induce mRNA expression of Cpt1 through a PPAR{alpha}-independent mechanism (37,38). These findings suggest possible involvement of another mechanism unrelated to PPAR{alpha} in the FO ingestion-induced regulation of fatty acid catabolism-related genes.

FO ingestion induced ME and ß-oxidation activity in the small intestine. ME, which is a representative lipogenic enzyme in the liver and adipose tissue, catalyzes the synthesis of pyruvate and NADPH from malate and NADP+. NADPH generated by the reaction then promotes fatty acid synthesis by lipogenic enzymes such as FASN and ACACA (39). The ME reaction is thought to supply ~50% of the NADPH required for palmitate synthesis produced by the FASN reaction (40–42). Northern blot analysis, however, revealed that the expression of Fasn and Acaca in the small intestine were quite low compared with the liver and that the expression of Fasn was less in mice fed the 8% FO diet compared with mice fed the 30% TG diet, although the expression of Mod1 was greater in mice fed the 8% FO diet. Therefore, it is unlikely that NADPH generated by ME links to fatty acid synthesis catalyzed by FASN and ACACA. On the other hand, FO ingestion induced {omega}-oxidation activity in the small intestine. CYP4A is a cytochrome P450 enzyme, which catalyzes the {omega}-oxidation of fatty acids and CYP4A subfamily enzymes require NADPH as a coenzyme (25). Therefore, the increased ME activity in the small intestine could stimulate {omega}-oxidation of fatty acids by generating NADPH, an efficient stimulator of fatty acid catabolism in the small intestine.

FO ingestion not only increases hepatic fatty acid catabolic enzyme activities (10–12) but also reduces lipogenic enzyme activities in the liver (6–9). Kim et al. (7) reported that 5-wk ingestion of a diet containing FO decreased TG and cholesterol concentrations in the liver compared with a diet containing safflower oil in C57BL/6J mice. They also demonstrated that FO ingestion decreased hepatic mRNA expression of sterol regulatory element binding protein 1c and sterol regulatory element-dependent genes, including Fasn, Acaca, and stearoyl-CoA desaturase-1, compared with safflower oil rich in (n-6) PUFA. Consistent with previous reports, we demonstrated that FO ingestion reduced hepatic mRNA expression of Fasn and Acaca. Thus, in addition to increasing fatty acid catabolism in the intestine and liver, the reduction of fatty acid synthesis in the liver might be another important factor responsible for the beneficial effects of FO. Flachs et al. (43) reported that PUFA, including DHA and eicosapentaenoic acid, upregulated mitochondrial biogenesis and induced ß-oxidation in WAT. Furthermore, Tsuboyama-Kasaoka et al. (44) demonstrated that FO ingestion induces mRNA expression of Ucp3, which is related to thermogenesis in skeletal muscles. These metabolic effects of FO ingestion on WAT or skeletal muscle might also contribute to the antiobesity and hypolipidemic effects of FO.

In this study, ingestion of FO rich in (n-3) PUFA reduced fat in diet-induced obesity-prone C57BL/6J mice associated with stimulating fatty acid catabolism in the small intestine. These findings might provide clues to understanding the effects of (n-3) PUFA on lipid metabolism and help to clarify the role of intestinal fatty acid catabolism in the control of systemic lipid metabolism.


   FOOTNOTES
 
1 Author disclosures: T. Mori, H. Kondo, T. Hase, I. Tokimitsu, and T. Murase, no conflicts of interest. Back

2 Supplemental Table 1 is available with the online posting of this paper at jn.nutrition.org. Back

3 Abbreviations used: ACACA, acetyl-CoA carboxylase {alpha}; ACADM, medium-chain acyl-CoA dehydrogenase; ACCA, acetyl-CoA acyltransferase; ACOT, acyl-CoA thioesterase; ACOX1, acyl-CoA oxidase 1; CYP4A, cytochrome P450 4A; CPT1a, carnitine palmitoyltransferase 1a; DHA, docosahexaenoic acid; FASN, fatty acid synthase; FO, fish oil; 2% FO diet, diet containing 28% triacylglycerol oil plus 2% FO; 4% FO diet, diet containing 26% triacylglycerol oil plus 4% FO; 5% triacylglycerol diet, diet containing 5% triacylglycerol oil; 8% FO diet, diet containing 22% triacylglycerol oil plus 8% FO; 30% triacylglycerol diet, diet containing 30% triacylglycerol oil; ME, malic enzyme; MOD1, NADP+-dependent cytosolic malic enzyme; TG, triacylglycerol; UCP2, uncoupling protein 2; WAT, white adipose tissue. Back

Manuscript received 6 July 2007. Initial review completed 26 July 2007. Revision accepted 1 October 2007.


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 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
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