Elsevier

Molecular Metabolism

Volume 6, Issue 12, December 2017, Pages 1563-1573
Molecular Metabolism

Original Article
A polyphenol-rich cranberry extract reverses insulin resistance and hepatic steatosis independently of body weight loss

https://doi.org/10.1016/j.molmet.2017.10.003Get rights and content
Under a Creative Commons license
open access

Highlights

  • CE was shown to prevent obesity and its metabolic complications in DIO-mice.

  • CE did not reverse obesity but alleviated liver steatosis and glucose intolerance.

  • Liver inflammation was blunted in CE-treated mice.

  • CE treatment expanded Akkermansia muciniphila and Barnesiella in the gut microbiota.

  • CE targets the gut-liver axis to primarily improve glucose homeostasis.

Abstract

Objective

Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice.

Methods

Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200 mg/kg, Chow + CE, HFHS + CE) or vehicle (Chow, HFHS) for 8 additional weeks.

Results

CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS + CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARα) and downregulation of several pro-inflammatory genes (eg, COX2, TNFα) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS + CE mice. The gut microbiota of HFHS + CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls.

Conclusions

Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.

Author Video

Download : Download video (33MB)

Author Video. Watch what authors say about their articles

Keywords

Akkermansia
Barnesiella
Obesity
Vaccinium macrocarpon
Flavonoids

Cited by (0)