scholarly journals Mgll Knockout Mouse Resistance to Diet-Induced Dysmetabolism Is Associated with Altered Gut Microbiota

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2705
Author(s):  
Niokhor Dione ◽  
Sébastien Lacroix ◽  
Ulrike Taschler ◽  
Thomas Deschênes ◽  
Armita Abolghasemi ◽  
...  

Monoglyceride lipase (MGLL) regulates metabolism by catabolizing monoacylglycerols (MAGs), including the endocannabinoid 2-arachidonoyl glycerol (2-AG) and some of its bioactive congeners, to the corresponding free fatty acids. Mgll knockout mice (Mgll−/−) exhibit elevated tissue levels of MAGs in association with resistance to the metabolic and cardiovascular perturbations induced by a high fat diet (HFD). The gut microbiome and its metabolic function are disrupted in obesity in a manner modulated by 2-arachidonoyl glycerol (2-AG’s) main receptors, the cannabinoid CB1 receptors. We therefore hypothesized that Mgll−/− mice have an altered microbiome, that responds differently to diet-induced obesity from that of wild-type (WT) mice. We subjected mice to HFD and assessed changes in the microbiomes after 8 and 22 weeks. As expected, Mgll−/− mice showed decreased adiposity, improved insulin sensitivity, and altered circulating incretin/adipokine levels in response to HFD. Mgll−/− mice on a chow diet exhibited significantly higher levels of Hydrogenoanaerobacterium, Roseburia, and Ruminococcus than WT mice. The relative abundance of the Lactobacillaceae and Coriobacteriaceae and of the Lactobacillus, Enterorhabdus, Clostridium_XlVa, and Falsiporphyromonas genera was significantly altered by HFD in WT but not Mgll−/− mice. Differently abundant families were also associated with changes in circulating adipokine and incretin levels in HFD-fed mice. Some gut microbiota family alterations could be reproduced by supplementing 2-AG or MAGs in culturomics experiments carried out with WT mouse fecal samples. We suggest that the altered microbiome of Mgll−/− mice contributes to their obesity resistant phenotype, and results in part from increased levels of 2-AG and MAGs.

2021 ◽  
Author(s):  
Antwi-Boasiako Oteng ◽  
Sei Higuchi ◽  
Alexander S. Banks ◽  
Rebecca A. Haeusler

Objective: Murine-specific muricholic acids (MCAs) are reported to protect against obesity and associated metabolic disorders. However, the response of mice with genetic depletion of MCA to an obesogenic diet has not been evaluated. We used Cyp2c-deficient (Cyp2c-/-) mice, which lack MCAs and thus have a human-like bile acid (BA) profile, to directly investigate the potential role of MCAs in diet-induced obesity. Methods: Male and female Cyp2c-/- mice and wild-type controls were fed a standard chow diet or a high fat diet (HFD) for 18 weeks. We measured BA composition from a pool of liver, gallbladder, and intestine, as well as weekly body weight, food intake, lean and fat mass, systemic glucose homeostasis, energy expenditure, intestinal lipid absorption, fecal lipid, and energy content. Results: Cyp2c deficiency depleted MCAs and caused other changes in BA composition, namely a decrease in the ratio of 12α-hydroxylated (12α-OH) BAs to non-12α-OH BAs, without altering the total BA levels. While wild-type male mice became obese after HFD-feeding, Cyp2c-/- male mice were protected from obesity and associated metabolic dysfunctions. Cyp2c-/- male mice also showed reduced intestinal lipid absorption and increased lipid excretion, which was reversed by oral gavage with the 12α-OH BA, taurocholic acid. Cyp2c-/- mice also showed increased liver damage, which appeared stronger in females. Conclusion: MCA does not protect against diet-induced obesity but may protect against liver injury. Reduced lipid absorption in Cyp2c-deficient male mice is potentially due to a reduced ratio of 12α-OH/non-12α-OH BAs.


iScience ◽  
2021 ◽  
Vol 24 (2) ◽  
pp. 102077
Author(s):  
Hu Hua ◽  
Yue Zhang ◽  
Fei Zhao ◽  
Ke Chen ◽  
Tong Wu ◽  
...  

2021 ◽  
Author(s):  
Xiao Guo ◽  
Xuedan Cao ◽  
Xiugui Fang ◽  
Ailing Guo ◽  
Erhu Li

In this study, Ougan juice (OJ) and lactic acid bacteria fermented Ougan juice (FOJ) were investigated individually for their capability of preventing obesity in high-fat diet (HFD)-fed C57BL/6J mice. After...


2022 ◽  
Author(s):  
Ying Lan ◽  
Qingyang Sun ◽  
Zhiyuan Ma ◽  
Jing Peng ◽  
Mengqi Zhang ◽  
...  

Obesity has been reported to be associated with gut microbiome dysbiosis. seabuckthorn fruits are traditionally used in Tibetan foods and medicines for thousands of years. Seabuckthorn polysaccharide (SP) is one...


2021 ◽  
Author(s):  
Zhen Shi ◽  
Zhiyuan Fang ◽  
Xinxing Gao ◽  
Hao Yu ◽  
Yiwei Zhu ◽  
...  

Nuciferine (NF) has received extensive attention for its medicinal value in the treatment of metabolic diseases, such as obesity, but the effects of NF on obesity-related intestinal permeability, autophagy and...


2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.


PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186216 ◽  
Author(s):  
Chenxi Cui ◽  
Yanyan Li ◽  
Hang Gao ◽  
Hongyan Zhang ◽  
Jiaojiao Han ◽  
...  

2019 ◽  
Vol 71 ◽  
pp. 72-88 ◽  
Author(s):  
Zahra Safari ◽  
Magali Monnoye ◽  
Peter M. Abuja ◽  
Mahendra Mariadassou ◽  
Karl Kashofer ◽  
...  

2019 ◽  
Vol 317 (6) ◽  
pp. E973-E983 ◽  
Author(s):  
Annie Hasib ◽  
Chandani K. Hennayake ◽  
Deanna P. Bracy ◽  
Aimée R. Bugler-Lamb ◽  
Louise Lantier ◽  
...  

Extracellular matrix hyaluronan is increased in skeletal muscle of high-fat-fed insulin-resistant mice, and reduction of hyaluronan by PEGPH20 hyaluronidase ameliorates diet-induced insulin resistance (IR). CD44, the main hyaluronan receptor, is positively correlated with type 2 diabetes. This study determines the role of CD44 in skeletal muscle IR. Global CD44-deficient ( cd44−/−) mice and wild-type littermates ( cd44+/+) were fed a chow diet or 60% high-fat diet for 16 wk. High-fat-fed cd44−/− mice were also treated with PEGPH20 to evaluate its CD44-dependent action. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (ICv). High-fat feeding increased muscle CD44 protein expression. In the absence of differences in body weight and composition, despite lower clamp insulin during ICv, the cd44−/− mice had sustained glucose infusion rate (GIR) regardless of diet. High-fat diet-induced muscle IR as evidenced by decreased muscle glucose uptake (Rg) was exhibited in cd44+/+ mice but absent in cd44−/− mice. Moreover, gastrocnemius Rg remained unchanged between genotypes on chow diet but was increased in high-fat-fed cd44−/− compared with cd44+/+ when normalized to clamp insulin concentrations. Ameliorated muscle IR in high-fat-fed cd44−/− mice was associated with increased vascularization. In contrast to previously observed increases in wild-type mice, PEGPH20 treatment in high-fat-fed cd44−/− mice did not change GIR or muscle Rg during ICv, suggesting a CD44-dependent action. In conclusion, genetic CD44 deletion improves muscle IR, and the beneficial effects of PEGPH20 are CD44-dependent. These results suggest a critical role of CD44 in promoting hyaluronan-mediated muscle IR, therefore representing a potential therapeutic target for diabetes.


2016 ◽  
Vol 22 ◽  
pp. 189-200 ◽  
Author(s):  
Jing Sun ◽  
Fazheng Ren ◽  
Ling Xiong ◽  
Liang Zhao ◽  
Huiyuan Guo

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