Diverse effects of different Akkermansia muciniphila genotypes on Brown adipose tissue inflammation and whitening in a high-fat-diet murine model

Background: The purpose of this study was to investigate the differences in the metabolic protective effects of Akkermansia muciniphila (A.muciniphila) genotypes on high-fat diet mice and explore possible mechanisms. Methods: Male C57BL/6 mice were randomly divided into 6 groups, including high-fat diet (HFD)+A. muciniphila I/II/PBS group, normal control diet (NCD)+A. muciniphila I/II/PBS group, respectively. Dietary intervention and A. muciniphila gavage were performed simultaneously. Blood glucose and lipid metabolism, brown adipose morphology and activities, and intestinal barrier function were examined after the mice were sacrificed. Results: A.muciniphila gavage improved the impaired glucose tolerance, hyperlipidemia and liver steatosis in HFD mice, and that A. muciniphila II (Amuc_GP25) was not as effective as A. muciniphila I (Amuc_GP01). This phenomenon might be because Amuc_GP01 intervention significantly inhibited brown adipose tissue whitening and inflammation induced by HFD, by repairing the intestinal barrier and relieving endotoxemia. Amuc_GP25 did not display the same results as Amuc_GP01 in HFD mice but had stronger effects in the NCD mice. Conclusions: This study reveals the distinct functions of different A. muciniphila genotypes on diet-induced obesity, suggesting that different A. muciniphila genotypes may affect pathological conditions differently through distinct action pathways.