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. 2017 Oct;25(4):919-930.
doi: 10.1016/j.jfda.2016.11.015. Epub 2017 Feb 16.

The regulatory effects of fish oil and chitosan on hepatic lipogenic signals in high-fat diet-induced obese rats

Chen-Yuan Chiu  1   2 , Tien-Chia Chang  3 , Shing-Hwa Liu  2   4   5 , Meng-Tsan Chiang  3
Affiliations

The regulatory effects of fish oil and chitosan on hepatic lipogenic signals in high-fat diet-induced obese rats

Chen-Yuan Chiu et al. J Food Drug Anal. 2017 Oct.

Abstract

The present study investigated the regulatory effects of fish oil and chitosan on the signals of hepatic lipid metabolism and the postulated mechanism in high-fat diet-induced obese rats. Diet supplementation of chitosan and fish oil efficiently suppressed the increased weights in body and livers of high-fat diet-fed rats. Supplementation of chitosan and fish oil significantly decreased the activities of hepatic lipid biosynthesis-related enzymes and efficiently regulated plasma lipoprotein homeostasis. Both chitosan and fish oil significantly ameliorated the alterations in the protein expressions of hepatic lipogenic transcription factors (LXRα and PPARα), and could also significantly regulate the downstream hepatic lipogenic genes (FAS, HMGCR, CYP7A1, FATP, FABP, AOX, and ABCA) expressions in high-fat diet-fed rats. These results suggest that both fish oil and chitosan exerts downregulative effects on hepatic lipid metabolism in high-fat diet-induced obese rats via the LXRα inhibition and PPARα activation, which further affect the expressions of hepatic lipogenesis-associated genes.

Keywords: chitosan; fish oil; gene expressions; high-fat diet; lipogenesis.

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Conflict of interest statement

Conflicts of interest

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Effects of chitosan and fish oil on body weights of high-fat diet-fed rats. The changes of body weights in rats fed with high-fat (HF) diet in the presence or absence of chitosan (CS, 5%) or fish oil (O, 5%) or as combination for 5 weeks were shown. Results are expressed as mean ± SD for each group (n = 8). * p < 0.05 as compared with HF diet alone group. § p < 0.05 as compared with HF diet supplemented with 5% fish oil group. # p < 0.05 as compared with HF diet supplemented with 5% chitosan group. ND = normal control diet; SD = standard deviation.
Figure 2
Figure 2
Effects of chitosan and fish oil on hepatic lipid profile and enzyme activity of lipid biosynthesis of high-fat (HF) diet-fed rats. (A) Histological analysis of livers isolated from rats fed with different experimental diets for 5 weeks is shown. Tissue sections were stained with H&E. The levels of (B) triglyceride, (C) total cholesterol, (D) fatty acid synthase, and (E) HMG-CoA reductase in livers of rats fed with different experimental diets for 5 weeks was shown. Results are expressed as mean ± SD for each group (n = 8). Scale bar = 100 μm. * p < 0.05 as compared with HF diet alone group. § p < 0.05 as compared with HF diet supplemented with 5% fish oil group. # p < 0.05 as compared with HF diet supplemented with 5% chitosan group. CS = chitosan; FO = fish oil; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; H&E = hematoxylin and eosin; ND = normal control diet; SD = standard deviation.
Figure 3
Figure 3
Effects of chitosan and fish oil on hepatic protein expressions of lipid metabolism of high-fat (HF) diet-fed rats. Protein expressions of (A) LXRα, and (B) PPARα were measured by Western blotting. Densitometric analysis for protein levels corrected to each internal control was shown. Results are expressed as mean ± SD for each group (n = 4–6). * p < 0.05 as compared with HF diet alone group. § p < 0.05 as compared with HF diet supplemented with 5% fish oil group. # p < 0.05 as compared with HF diet supplemented with 5% chitosan group. CS = chitosan; FO = fish oil; HF = high-fat; LXRα = liver X receptor alpha; ND = normal control diet; PPARα = peroxisome proliferator-activated receptor alpha; SD = standard deviation.
Figure 4
Figure 4
Effects of chitosan and fish oil on hepatic gene expressions of fatty acid biosynthesis, transport, and β-oxidation in high-fat (HF) diet-fed rats. Hepatic gene expressions of fatty acid biosynthesis [(A) SREBP1c and (B) FAS], (B) transport (FABP4), and (C) β-oxidation (AOX1) were determined by qRT-PCR. Results are expressed as mean ± SD for each group (n = 4–6). * p < 0.05 as compared with HF diet alone group. § p < 0.05 as compared with HF diet supplemented with 5% fish oil group. # p < 0.05 as compared with HF diet supplemented with 5% chitosan group. AOX1 = acyl-CoA oxidase 1; CS = chitosan; FABP4 = fatty acid binding proteins-4; FAS = fatty acid synthase; FO = fish oil; HF = high-fat; ND = normal control diet; qRT-PCR = quantitative reverse transcription polymerase chain reaction analysis; SD = standard deviation; SREBP1c = sterol regulatory element-binding protein-1c.
Figure 5
Figure 5
Effects of chitosan and fish oil on hepatic gene expressions of cholesterol biosynthesis, metabolism, and excretion in high-fat (HF) diet-fed rats. Hepatic gene expressions of cholesterol (A) biosynthesis (HMGCR), (B) metabolism (CYP7A1), and (C) excretion (ABCA1) were determined by qRT-PCR. Results are expressed as mean ± SD for each group (n = 4–6). * p < 0.05 as compared with HF diet alone group. § p < 0.05 as compared with HF diet supplemented with 5% fish oil group. # p < 0.05 as compared with HF diet supplemented with 5% chitosan group. ABCA1 = ATP-binding cassette subfamily A member-1; CS = chitosan; CYP7A1 = cytochrome P450 7A1; FO = fish oil; HF = high-fat; HMGCR = 3-hydroxy-3-methylglutaryl coenzyme A reductase; ND = normal control diet; qRT-PCR = quantitative reverse transcription polymerase chain reaction analysis; SD = standard deviation.
Figure 6
Figure 6
Schematic model. The schematic describes a proposed model that fish oil can exert antiobesity effects with chitosan on the downregulation of hepatic lipid metabolism via LXRα inhibition and PPARα promotion-mediated downstream lipogenesis inhibition, which can ameliorate lipid biosynthesis and accumulation in the liver. ⊖ indicates activation. ⊕ indicates inhibition. Ⓐ indicates the additive effect of fish oil with chitosan. Ⓢ indicates the synergistic effect of fish oil with chitosan. ABCA1 = ATP-binding cassette subfamily A member-1; AOX1 = acyl-CoA oxidase 1; CHOL = cholesterol; CYP7A1 = cytochrome P450 7A1; FA = fatty acid; FABP4 = fatty acid binding proteins-4; FAS = fatty acid synthase; HMGCR = 3-hydroxy-3-methylglutaryl coenzyme A reductase; LXRα = liver X receptor alpha; MW = molecular weight; PPARα = peroxisome proliferator-activated receptor alpha; SREBP1c = sterol regulatory element-binding protein-1c.
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Grants and funding

This study was supported by a grant (MOST103-2313-B-019-001-MY3) from the Ministry of Science and Technology, Taiwan (R.O.C).