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

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.

Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

“…Accumulating evidence supports the health-promoting effects of A. muciniphila [ 34 ] because it improved several metabolic parameters in overweight and obese human subjects [ 25 ]. Recently, it has been found that pasteurization of A. muciniphila increases its beneficial effects on metabolism [ 35 ]. This is in agreement with a clinical trial which revealed that compared to the placebo, pasteurized A. muciniphila significantly improved insulin sensitivity, decreased insulinemia and plasma total cholesterol in the overweight and obese subjects [ 25 ].…”

Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased Akkermansia muciniphila in Mice

“…Up-regulation in the mRNA expression of Intectin has already been demonstrated with inulin-type fibers but never with polyphenol-rich prebiotics [ 25 ]. Recently, we demonstrated that administration of Akkermansia muciniphila in mice attenuated the down-regulation of Intectin that occurred, in response to HFD [ 79 ]. This represents another mechanism by which rhubarb extract supplementation can contribute to reinforce the gut barrier function [ 25 , 80 , 81 ].…”

Non-Viable Lactobacillus johnsonii JNU3402 Protects against Diet-Induced Obesity

“…However, most studies investigating the effects of probiotics on host health, including these studies, have been performed using live bacteria. Although some reports have shown that NV probiotics play a role in the host immune system and reduce diet-induced obesity and insulin resistance [ 19 , 20 , 21 ], little is still known about the effect of NV probiotic bacteria on energy homeostasis in HFD-fed mice. Here, the effect of NV-LJ3402 on diet-induced obesity was examined, and the results demonstrated that NV-LJ3402 attenuates body weight gain and adiposity in HFD-fed mice by enhancing the expression of genes critical for energy dissipation in WAT.…”