Nutr Res Pract.  2020 Dec;14(6):580-592. 10.4162/nrp.2020.14.6.580.

Hypotriglyceridemic effects of brown seaweed consumption via regulation of bile acid excretion and hepatic lipogenesis in high fat diet-induced obese mice

• Han AR
• Kim JH
• Kim E
• Cui J
• Chai IS
• Zhang G
• Lee Y

• KMID: 2508792
• DOI: http://doi.org/10.4162/nrp.2020.14.6.580

Abstract

BACKGROUND/OBJECTIVES
The present study aimed to further investigate the potential health beneficial effects of long-term seaweed supplementation on lipid metabolism and hepatic functions in DIO mice.
MATERIALS/METHODS
Four brown seaweeds (Undaria pinnatifida [UP], Laminaria japonica [LJ], Sargassum fulvellum [SF], or Hizikia fusiforme [HF]) were added to a high fat diet (HFD) at a 5% ratio and supplemented to C57BL/6N mice for 16 weeks. Triglycerides (TGs) and total cholesterol (TC) in the liver, feces, and plasma were measured. Fecal bile acid (BA) levels in feces were monitored. Hepatic insulin signaling- and lipogenesis-related proteins were evaluated by Western blot analysis.
RESULTS
Fasting blood glucose levels were significantly reduced in the LJ, SF, and HF groups compared to the HFD group by the end of 16-week feeding period. Plasma TG levels and hepatic lipid accumulation were significantly reduced in all 4 seaweed supplemented groups, whereas plasma TC levels were only suppressed in the UP and HF groups compared to the HFD group. Fecal BA levels were significantly elevated by UP, LJ, and SF supplementation compared to HFD feeding only. Lastly, regarding hepatic insulin signaling-related proteins, phosphorylation of 5′-AMP-activated protein kinase was significantly up-regulated by all 4 types of seaweed, whereas phosphorylation of protein kinase B was up-regulated only in the SF and HF groups. Lipogenesis-related proteins in the liver were effectively down-regulated by HF supplementation in DIO mice.
CONCLUSIONS
Brown seaweed consumption showed hypotriglyceridemic effects in the prolonged DIO mouse model. Specifically, combinatory regulation of BA excretion and lipogenesis-related proteins in the liver by seaweed supplementation contributed to the reduction of plasma and hepatic TG levels, which inhibited hyperglycemia in DIO mice. Thus, the discrepant and species-specific functions of brown seaweeds provide novel insights for the selection of future targets for therapeutic agents.

Keyword

Seaweed; liver; lipogenesis; bile; mice

Figure

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  Fig. 1 Alteration of plasma FBG levels during the 16-week period of HFD or HFD supplementation with 4 types of seaweed in C57BL/6N mice. (A) Plasma FBG levels at weeks 4, 8, 12, and 16 of the experimental diet present significant differences between the seaweed supplemented groups compared to the HFD group every 4 weeks. (B) Alteration of plasma FBG levels measured every 4 weeks during the entire 16 weeks of feeding in C57BL/6N mice. Values are the mean ± standard error of the mean (n = 6 mice per group). An asterisk indicates a significant difference compared to either the HFD group (P < 0.05) or week 4 values of each group in (A) and (B), respectively.FBG, fasting blood glucose; HFD, high fat diet; UP, Undaria pinnatifida; LJ, Laminaria japonica; SF, Sargassum fulvellum; HF, Hizikia fusiforme.

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  Fig. 2 Effects of seaweed supplementation on plasma TC and TG levels of C57BL/6N mice fed a HFD or seaweed supplemented HFD for 16 weeks. Values are the mean ± standard error of the mean (n = 6 mice per group). An asterisk indicates a significant difference compared to the HFD group (P < 0.05).TC, total cholesterol; TG, triglyceride; HFD, high fat diet; UP, Undaria pinnatifida; LJ, Laminaria japonica; SF, Sargassum fulvellum; HF, Hizikia fusiforme.

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  Fig. 3 Protective effects of seaweed supplementation on hepatic lipid accumulation in diet-induced obese mice. (A) Representative hematoxylin and eosin staining of livers from mice fed a HFD or seaweed supplemented HFD for 16 weeks, (B) Liver TG and TG contents of mice fed a HFD or seaweed supplemented HFD for 16 weeks (n = 5–6). Values are the mean ± standard error of the mean. An asterisk indicates a significant difference compared to the HFD group (P < 0.05).HFD, high fat diet; UP, Undaria pinnatifida; LJ, Laminaria japonica; SF, Sargassum fulvellum; HF, Hizikia fusiforme; TC, total cholesterol; TG, triglyceride.

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  Fig. 4 Alterations of fecal TC, TG, and BA contents by seaweed supplementation during the latter half of the HFD feeding period in C57BL/6N mice. Feces samples from individual mouse cages were collected in order to measure fecal TC, TG, and BA levels as described in the Methods. Values are the mean ± standard error of the mean (n = 4–5). An asterisk in the bar graphs indicates a significant difference compared to HFD feeding only, whereas an asterisk in the connecting line graphs indicates a significant difference compared to week 8 (P < 0.05).HFD, high fat diet; UP, Undaria pinnatifida; LJ, Laminaria japonica; SF, Sargassum fulvellum; HF, Hizikia fusiforme; TC, total cholesterol; TG, triglyceride; BA, bile acid.

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  Fig. 5 Effects of insulin signaling-related proteins via seaweed supplementation in the livers of diet-induced obese mice. (A) Representative immunoblot analysis of phospho-AMPK and total AMPK, phospho-AKT, total AKT, and GAPDH levels in the liver, (B) Intensity of phospho-AMPK was normalized to total AMPK, and intensity of phospho-AKT was normalized to total AKT. Values are the mean ± standard error of the mean. An asterisk indicates a significant difference compared to the HFD group (P < 0.05).UP, Undaria pinnatifida; LJ, Laminaria japonica; SF, Sargassum fulvellum; HF, Hizikia fusiforme; AMPK, 5′-AMP-activated protein kinase; AKT, protein kinase B; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HFD, high fat diet.

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  Fig. 6 Effects of lipogenesis-related proteins via seaweed supplementation in the livers of diet-induced obese mice. (A) Representative immunoblot analysis of ACC, FAS, SREBP-1c, and GAPDH in the liver, (B) Intensities of ACC, FAS, and SREBP-1c were normalized to GAPDH. Values are the mean ± standard error of the mean. An asterisk indicates a significant difference compared to the HFD group (P < 0.05).UP, Undaria pinnatifida; LJ, Laminaria japonica; SF, Sargassum fulvellum; HF, Hizikia fusiforme; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; SREBP-1c, sterol regulatory element-binding protein-1c; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HFD, high fat diet.

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