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.
Nothing is known about the potential implication of gut microbiota in skeletal muscle disorders. Here, we provide evidence that fecal microbiota composition along with circulating levels of shortchain fatty acids (SCFAs) and related metabolites are altered in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared with healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice rescued muscle strength and autophagy, and prevented inflammation associated with excessive endocannabinoid signaling at CB1 receptors to the same extent as deflazacort (DFZ), the standard palliative care for DMD. In LPSstimulated C2C12 myoblasts, NaB reduces inflammation, promotes autophagy, and prevents dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene, in a manner depending on the activation of GPR109A and PPARc receptors. In sum, we propose a novel disease-modifying approach in DMD that may have benefits also in other muscular dystrophies.
We investigated the influence of different dietary formulation of n-3 polyunsaturated fatty acids (PUFA) on rat tissue fatty acid (FA) incorporation and consequent modulation of their bioactive metabolite N-acylethanolamines (NAE). For 10 weeks, rats were fed diets with 12% of fat from milk + 4% soybean oil and 4% of oils with different n-3 PUFA species: soybean oil as control, linseed oil rich in α-linolenic (ALA), Buglossoides arvensis oil rich in ALA and stearidonic acid (SDA), fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), Nannochloropsis microalga oil rich in EPA or Schizochytrium microalga oil rich in DHA. FA and NAE profiles were determined in plasma, liver, brain and adipose tissues. Different dietary n-3 PUFA distinctively influenced tissue FA profiles and consequently NAE tissue concentrations. Interestingly, in visceral adipose tissue the levels of N-arachidonoylethanolamide (AEA) and N-docosahexaenoylethanolamide (DHEA), NAE derived from arachidonic acid (AA) and DHA, respectively, significantly correlated with NAE in plasma, and circulating DHEA levels were also correlated with those in liver and brain. Circulating NAE derived from stearic acid, stearoylethanolamide (SEA), palmitic acid and palmitoylethanolamide (PEA) correlated with their liver concentrations. Our data indicate that dietary n-3 PUFA are not all the same in terms of altering tissue FA and NAE concentrations. In addition, correlation analyses suggest that NAE levels in plasma may reflect their concentration in specific tissues. Given the receptor-mediated tissue specific metabolic role of each NAE, a personalized formulation of dietary n-3 PUFA might potentially produce tailored metabolic effects in different pathophysiological conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.