Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice

Gut Microbes. 2020 Sep 2;11(5):1231-1245. doi: 10.1080/19490976.2020.1737307. Epub 2020 Mar 13.

Abstract

Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.

Keywords: Akkermansia muciniphila; brown adipose tissue metabolism; carbohydrates absorption; indirect calorimetry; intestinal turnover; mice; motor activity; obesity; pasteurization; perilipins; white adipose tissue metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / physiology
  • Adipose Tissue, Brown / physiology
  • Akkermansia
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Diet, High-Fat
  • Dietary Carbohydrates / metabolism
  • Energy Metabolism*
  • Feces / chemistry*
  • Gastrointestinal Microbiome*
  • Gene Expression Regulation
  • Intestinal Absorption
  • Intestinal Mucosa / cytology
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism*
  • Obesity / prevention & control*
  • Oxygen Consumption
  • Pasteurization
  • Perilipin-2 / genetics
  • Perilipin-2 / metabolism
  • Physical Conditioning, Animal
  • Weight Gain

Substances

  • Carrier Proteins
  • Dietary Carbohydrates
  • Perilipin-2
  • Plin2 protein, mouse

Supplementary concepts

  • Akkermansia muciniphila

Grant support

This work was supported by the Fonds de la Recherche Scientifique (FNRS FRFS-WELBIO) under the grants [WELBIO-CR-2017C-02] and [WELBIO-CR-2019C-02R], the Funds Baillet-Latour under the grant Grant For Medical Research 2015 and the European Research Council under the grants ERC Starting Grant 2013 Starting grant [336452-ENIGMO] and [ERC Advanced Grant 250172] (Microbes Inside) and the Spinoza Award of the Netherlands Organization for Scientific Research.