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Cited by 103Gut microbiota and healthFatty Acid Research and HealthSeaweed-derived Bioactive Compounds

Regulatory Efficacy of the Polyunsaturated Fatty Acids from Microalgae Spirulina platensis on Lipid Metabolism and Gut Microbiota in High-Fat Diet Rats

Open access
Li, Tian-Tian, Liu, Yuan-Yuan, Wan, Xu-Zhi, Huang, Zi-Rui, Liu, Bin, Zhao, Chao·2018·International Journal of Molecular Sciences
DOI 10.3390/ijms19103075PMC PMC6213792
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Abstract

Ultra-high performance liquid chromatography coupled with photo-diode array detector and electrospray ionization-mass spectrometry was employed to analyze the major fatty acids in Spirulina platensis 95% ethanol extract (SPL95). The effects of SPL95 on hepatoprotection were evaluated, including liver tissue histopathology, liver, and serum biochemical analysis. The active principle of SPL95 revealed a hypolipidemic effect, as indicated by down-regulating the mRNA and protein levels of sterol regulatory element-binding transcription factor-1c, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, acetyl CoA carboxylase pathway, and upregulating adenosine 5′-monophosphate-activated protein kinase-α in liver. SPL95 enriched the beneficial bacteria, including Prevotella, Alloprevotella, Porphyromonadaceae, Barnesiella, and Paraprevotella. Treatment with SPL95 led to a decrease in microbes, such as Turicibacter, Romboutsia, Phascolarctobacterium, Olsenella, and Clostridium XVIII, which were positively correlated with serum triglyceride, total cholesterol, and low-density-lipoprotein cholesterol levels, but negatively correlated with the serum high-density-lipoprotein cholesterol levels. These results provide evidence that the fatty acid from SPL95 may be used as a novel adjuvant therapy and functional food to regulate gut microbiota in obese and diabetic individuals.

AI snapshot

Written from the paper’s full text.

TL;DR

SPL95, a 95% ethanol extract of *Spirulina platensis* rich in polyunsaturated fatty acids, improved lipid profiles and liver steatosis in high-fat-diet rats while remodeling gut microbiota. The effects were associated with upregulation of AMPK-α and downregulation of SREBP-1c, HMG-CoA, and ACC pathways.

Key findings

  • SPL95 contained ten major components, eight of which were polyunsaturated fatty acids, identified by UPLC-QTOF-MS/MS.
  • In high-fat-diet (HFD) rats, SPL95 reduced serum TG and TC by 49.41% and 35.68%, respectively, after 8 weeks; increased HDL-c by 47.22% at 4 weeks and 50.00% at 8 weeks; and lowered LDL-c at 4 and 8 weeks (p < 0.01).
  • SPL95 reduced liver TC, TG, LDL-c, ALT, AST, and FFA (p < 0.01), alleviated HFD-induced hepatic steatosis, upregulated AMPK-α, and downregulated SREBP-1c, HMG-CoA, and ACC at mRNA and protein levels.
  • SPL95 increased Prevotella, Alloprevotella, Porphyromonadaceae, Barnesiella, and Paraprevotella, and decreased Turicibacter, Romboutsia, Phascolarctobacterium, Olsenella, and Clostridium XVIII; Firmicutes fell from 81.51% to 57.09% and Bacteroidetes rose from 9.76% to 33.75% with SPL95 treatment.

Methods

  • SPL95 was prepared by 95% ethanol extraction of *S. platensis* and characterized using UPLC-QTOF-MS/MS.
  • Twenty-four male Wistar rats were divided into three groups (n = 8 each): normal-fat diet (NFD), high-fat diet (HFD), and HFD plus SPL95 (150 mg/kg/day by gavage) for 8 weeks. The HFD contained 67% normal diet, 20% sugar, 10% lard, and 3% cholesterol.
  • Outcomes included serum and liver biochemical assays, liver H&E histopathology, RT-qPCR and western blot for AMPK-α, SREBP-1c, HMG-CoA, and ACC, 16S rRNA V3–V4 sequencing of caecal contents, one-way ANOVA, and Spearman correlation analysis.

Limitations

  • Not stated in the paper. Evident from the text: the study used a small sample (n = 8 per group), only male Wistar rats, a single 8-week duration, and one SPL95 dose (150 mg/kg/day), with no dose-response or human validation.
  • Evident from the text: microbiota findings are correlational (Spearman analysis) and based on 16S genus-level profiling; no causal experiments (e.g., germ-free, antibiotic, or fecal transplant) were performed.
  • Evident from the text: SPL95 is a complex extract, and although the paper attributes effects to polyunsaturated fatty acids, individual compounds were not isolated and tested in vivo; no explicit safety or toxicity data are reported.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms19103075

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 11 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    HFD rats had significantly higher average body weight than NFD rats after 8 weeks.

    “In particular, the average weight of rats in the HFD group was observably higher than that in the normal-fat-diet (NFD) group (p < 0.01).”
    Quote in the paperSubstantial claim
  • Findingown data

    SPL95 treatment decreased serum TG and TC levels in HFD rats compared with HFD, by 49.41% and 35.68% respectively after 8 weeks.

    “TG and TC concentrations of the SPL95-treated group were lowered significantly when compared to those of HFD (p < 0.01).”
    • Also stated in: § 2.2. Effect of SPL95 on Body Weight and Serum Lipids of High-Fat-Diet Rats · plain
      “SPL95 had decreased serum TG and TC levels by 49.41% and 35.68% compared to those of the HFD group after 8 weeks’ supplement, respectively.”
    Quote in the paperSubstantial claim
  • Findingown data

    SPL95 treatment significantly increased serum HDL-c levels in HFD rats compared with HFD, by 47.22% at 4 weeks and 50.00% at 8 weeks.

    “The HDL-c levels of the SPL95 treatment group were significantly increased by 47.22% (p < 0.01) and 50.00% (p < 0.05) compared to those of the HFD group at the end of the 4th or 8th week, respectively.”
    Quote in the paperSubstantial claim
  • Findingown data

    SPL95 treatment significantly reduced body weight of HFD rats after 8 weeks compared with HFD.

    “Compared with the high fat diet-induced HFD model, the SPL95 significantly reduced the body weight of rats after 8 weeks of treatment.”
    Quote in the paperSubstantial claim
  • Findingown data

    SPL95 treatment significantly lowered serum LDL-c levels in HFD rats compared with HFD after 4 and 8 weeks.

    “Similarly, the LDL-c levels in the SPL95 group were significantly lower than those of the HFD group after 4 and 8 weeks of treatment (p < 0.01).”
    Quote in the paperSubstantial claim
  • May combine two claims. 17
  • Classified as probably not a substantial claim. 8
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    SPL95 contains ten major components, eight of which are polyunsaturated fatty acids.

    “The analysis of SPL95 resulted in the isolation of ten major components, eight of which were polyunsaturated fatty acids (Figure S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    SPL95 treatment alleviated hepatocyte injury and inflammation in hyperlipemia rats, with few fat droplets remaining.

    “However, treatment of liver with SPL95 alleviated hepatocyte injury and inflammation in hyperlipemia rats except for a few fat droplets (Figure 2C), which showed that SPL95 has displayed a protective effect on the liver.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In HFD rats, liver TC, TG, LDL-c, and FFA levels were significantly increased and HDL-c decreased compared with NFD, establishing the fatty liver model.

    “TC, TG, LDL-c, and free fatty acids (FFA) levels were significantly increased in the HFD group over those in the NFD group. Meanwhile, HDL-c levels were decreased, which showed that the fatty liver rat model has been successfully established.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SPL95 treatment significantly upregulated AMPK-α mRNA transcription in liver of HFD rats compared with HFD, similar to NFD.

    “The transcription level of AMPK-α was significantly upregulated by SPL95 compared to that of HFD rats (p < 0.01), which was similar to that observed in NFD rats.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingown data

    SPL95 treatment increased the relative abundance of Paraprevotella, which was positively correlated with serum HDL-c and liver AMPK-α.

    “More interestingly, the relative abundance of Paraprevotella showed positive relationships with serum HDL-c and liver AMPK-α.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The decreased microbes (Turicibacter, Romboutsia, Phascolarctobacterium, Erysipelotrichaceae, Clostridium_XlVa, Desulfovibrio) were positively correlated with serum TG, TC, and LDL-c levels, or liver SREBP-1c, HMG-CoA, and ACC levels, and negatively correlated with serum HDL-c and liver AMPK-α levels.

    “These strains were positively correlated with serum TG, TC, and LDL-c levels, or liver SREBP-1c, HMG-CoA, and ACC levels, while negatively with serum HDL-c and liver AMPK-α levels (Figure 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SPL95 treatment significantly decreased Firmicutes and increased Bacteroidetes in cecal contents of HFD rats.

    “Firmicutes (57.09%) was significantly decreased and Bacteroidetes (33.75%) was significantly increased over time with SPL95 treatment”
    • Also stated in: § 3. Discussion · plain
      “Moreover, SPL95 has decreased the percentage of Firmicutes and increased the percentage of Bacteroidetes in cecal contents.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SPL95 treatment significantly reduced liver TC, TG, LDL-c, ALT, AST, and FFA levels in HFD rats compared with HFD.

    “The therapeutic effect of the SPL95-supplemented group was determined by a decrease in lipid parameters, such as reductions in TC, TG, LDL-c, alanine transaminase (ALT), aspartate transaminase (AST), and FFA levels (p < 0.01).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HFD induced a significant phylum-wide shift between Bacteroidetes (9.76%) and Firmicutes (81.51%), which was modified by SPL95 treatment.

    “And HFD also induced a significant phylum-wide shift between Bacteroidetes (9.76%) and Firmicutes (81.51%), which was modified by SPL95 treatment during the active period.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    HMG-CoA is the rate-limiting enzyme in cholesterol biosynthesis and is regulated through a negative feedback mechanism.

    “The 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA), as the rate-limiting enzyme in cholesterol biosynthesis, is regulated through a negative feedback mechanism [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Deboseboyd, 2008, Feedback regulation of cholesterol synthesis: Sterol-accelerated ubiquitination and degradation of HMG-CoA reductase, Cell Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Ethanol extracts of many algae can change the gut microbiota.

    “Moreover, ethanol extracts of many algae can change the gut microbiota [6,14].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [6] Zhao, 2018, Bioactive compounds from marine macroalgae and their hypoglycemic benefits, Trends Food Sci. Technol. source

      Not checked in the free run.

    • cites [14] Zhao, C., Yang, C.F., Wai, S.T.C., Zhang, Y.B., Portillo, M.Y., Paoli, P., Wu, Y.J., Cheang, W.S., Liu, B., and Carpéné, C. (2018). Regulation of glucose metabolism by bioactive phytochemicals for the management of type 2 diabetes mellitus. Crit. Rev. Food Sci. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    AMPK is an intracellular energy sensor and a key factor regulating glucose and lipid metabolism.

    “The serine kinase adenosine 5’-monophosphate-activated protein kinase is an intracellular energy sensor that is a key factor that plays a role in regulating glucose and lipid metabolism [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] 2014, AMP-activated protein kinase: A key regulator of energy balance with many roles in human disease, J. Intern. Med. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ACC is the rate-limiting enzyme in de-novo lipogenesis and controls β-oxidation of fatty acids in mitochondria.

    “Acetyl CoA carboxylase (ACC), as the rate-limiting enzyme in de-novo lipogenesis, exists around the mitochondria and controls β-oxidation of fatty acids in the mitochondria [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Munday, 2002, Regulation of mammalian acetyl-CoA carboxylase, Biochem. Soc. Trans. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dietary factors play a role in regulating metabolism and are a safe and economic way to treat LMD.

    “Recent studies have shown that dietary factors play a role in regulating metabolism, and making it a safe and economic way to treat LMD [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Sarin, 2016, Effects of preoperative statin on liver reperfusion injury in major hepatic resection: A pilot study, Updates Surg. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    SPL95 may be beneficial for anti-hyperlipidemia and may reduce the risk of LMD.

    “Therefore, SPL95 may be beneficial for anti-hyperlipidemia and may reduce the risk of LMD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Alloprevotella and Ruminococcus are SCFA producers and negatively correlated with nonalcoholic fatty liver disease and LMD.

    “These bacteria are short chain fatty acid (SCFA) producers and negatively correlated with nonalcoholic fatty liver disease and LMD [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Shang, 2017, Dietary fucoidan improves metabolic syndrome in association with increased Akkermansia population in the gut microbiota of high-fat diet-fed mice, J. Funct. Foods. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Barnesiella spp. regulates the composition of the microbiota and optimizes host survival.

    “Moreover, Barnesiella spp. regulates the composition of the microbiota and optimizes host survival [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Ubeda, 2013, Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization, Infect. Immun. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Long-term intake of HFD is associated with metabolic syndrome in humans and rodents.

    “Long-term intake of HFD is associated with metabolic syndrome in humans and rodents [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Buettner, 2006, Defining high-fat-diet rat models: Metabolic and molecular effects of different fat types, J. Mol. Endocrinol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SREBP-1c preferentially enhances transcription of genes required for fatty acid synthesis.

    “Sterol regulatory element-binding transcription factor-1c (SREBP-1c) can preferentially enhance the transcription of genes required for fatty acid synthesis [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Cheng, 2017, (-)-Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high-fat diet, Mol. Nutr. Food Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Allopathic hypolipidemic drugs are available but have adverse effects and contraindications.

    “Allopathic hypolipidemic drugs are available at large in the market, but with their own adverse effects and contraindications [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Waness, 2008, Simvastatin-induced rhabdomyolysis and acute renal injury, Blood Purif. source

      Not checked in the free run.

20 of 20

  • The paper relies on this without support.

    The observed effects of SPL95 are attributable to its polyunsaturated fatty acids rather than other components.

    “Regulatory Efficacy of the Polyunsaturated Fatty Acids from Microalgae Spirulina platensis on Lipid Metabolism and Gut Microbiota in High-Fat Diet Rats”
    “Taken together, the polyunsaturated fatty acids from S. platensis were able to influence the lipid metabolism of Wistar rats fed with a high-fat diet.”

  • The paper relies on this without support.

    Findings in HFD Wistar rats can be extrapolated to obese and diabetic humans.

    “These results provide evidence that the fatty acid from SPL95 may be used as a novel adjuvant therapy and functional food to regulate gut microbiota in obese and diabetic individuals.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Li et al found that spirulina given for 8 weeks to high-fat diet rats increased HDL-C and lowered LDL-C, TG, and TC levels, and normalised hepatic steatosis with improvements in liver function tests.

    “Li et al found that spirulina given for 8 weeks increased HDL-C and lowered LDL-C, TG and TC levels when fed a high fat diet.29 Similar to other previous studies, it was also shown to normalise hepatic steatosis with improvements in liver function tests, including transaminases, free fatty acids and overall lipid profile.”

    From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [29]

  • Spirulina can alter gut microbiota to have lipid lowering effects, including increasing abundance of Prevotella, Porphyromonadaceae, Barnesiella, Paraprevotella, Alloprevotella, Ruminococcus, and Firmicutes.

    “Additionally, spirulina can alter gut microbiota to have lipid lowering effects. Studies have revealed an increase in abundance of Prevotella, Porphyromonadaceae, Barnesiella and Paraprevotella.”

    From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [29]

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Related

Authors
Li, T.-T., Liu, Y.-Y., Wan, X.-Z., Huang, Z.-R., Liu, B., & Zhao, C.
Affiliations
  • College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
  • Fujian Agriculture and Forestry University (CN)
  • Quanzhou Normal University (CN)
Corresponding author
  • Liu, Bin
  • Zhao, Chao
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2018-10-09
Volume
19
Issue
10
Pages
3075
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms19103075
PMC
PMC6213792
OpenAlex
W2897091331
Semantic Scholar
943985c91e95c4837d28f4b0f33679b49fa991b1
Cited by
103
References
37
Citations by year
2026: 8 · 2025: 16 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 18 · 2020: 13 · 2019: 10 · 2018: 1
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (2016J06009, 81741163)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
Keywords
Spirulina platensis, polyunsaturated fatty acids, high-fat diet, lipid metabolism, gut microbiota, hepatoprotection, hypolipidemic effect, SREBP-1c, HMG-CoA reductase, acetyl-CoA carboxylase, AMPK, serum lipids, cholesterol, triglycerides, functional foods, obesity, diabetes mellitus
MeSH terms
Gastrointestinal Microbiome, Animals, Biopsy, Chromatography, High Pressure Liquid, Fatty Acids, Unsaturated, Fatty Liver, Feces, Glucose, Lipids, Liver Function Tests, Biomarkers, Gene Expression, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, MAP Kinase Signaling System, Lipid Metabolism, Rats, Spirulina, Diet, High-Fat

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