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Diabetologia. 2018 Apr;61(4):919-931. doi: 10.1007/s00125-017-4520-z. Epub 2017 Dec 21.

Arctic berry extracts target the gut-liver axis to alleviate metabolic endotoxaemia, insulin resistance and hepatic steatosis in diet-induced obese mice.

Author information

1
Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, Laval University, Bureau Y4340, Québec City, QC, G1V 4G5, Canada.
2
Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada.
3
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Laval University, Québec City, QC, Canada.
4
Faculty of Pharmacy, Laval University, Québec City, QC, Canada.
5
Department of Biology, University of Ottawa, Ottawa, ON, Canada.
6
Populations Health and Optimal Health Practices Axis of the CHU-Québec Research Centre, Department of Social and Preventive Medicine, Laval University, Québec City, QC, Canada.
7
Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, Laval University, Bureau Y4340, Québec City, QC, G1V 4G5, Canada. andre.marette@criucpq.ulaval.ca.
8
Institute of Nutrition and Functional Foods, Laval University, Québec City, QC, Canada. andre.marette@criucpq.ulaval.ca.

Abstract

AIMS/HYPOTHESIS:

There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity.

METHODS:

Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota.

RESULTS:

Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2 ± 12.3, HFHS 153.9 ± 19.3, BBE 114.4 ± 14.3, CLE 82.5 ± 13.0, CRE 152.3 ± 24.4, ABE 90.6 ± 18.0, LGE 95.4 ± 10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l × min]: chow 14.3 ± 1.4, HFHS 31.4 ± 3.1, BBE 27.2 ± 4.0, CLE 17.7 ± 2.2, CRE 32.6 ± 6.3, ABE 22.7 ± 18.0, LGE 23.9 ± 2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice.

CONCLUSIONS/INTERPRETATION:

Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders.

DATA AVAILABILITY:

All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).

KEYWORDS:

Akkermansia muciniphila; Arctic berries; CEACAM-1; Gut microbiota; Insulin clearance

PMID:
29270816
DOI:
10.1007/s00125-017-4520-z
[Indexed for MEDLINE]

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