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      Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats

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          Abstract

          Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese ( fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

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          A rapid method of total lipid extraction and purification.

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            High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway

            Background & Aims While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet. Methods C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high–fat (60 kcal % fat) diet (HFD) for 8 weeks. Results HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice. Conclusions HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
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              Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

              ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 February 2017
                2017
                : 12
                : 2
                : e0171672
                Affiliations
                [1 ]Departamento de Fisiologia de la Nutricion, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F
                [2 ]Conacyt, Unidad de Genomica de Poblaciones, Instituto Nacional de Medicina Genomica, Mexico D.F
                [3 ]Department of Food Science and Technology, One Shields Avenue, University of California, Davis, Davis, California, United States of America
                [4 ]Department of Nutrition, One Shields Avenue, University of California, Davis, Davis, California, United States of America
                [5 ]Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine One Shields Avenue, University of California, Davis, Davis, California, United States of America
                University of Hawai'i at Manoa College of Tropical Agriculture and Human Resources, UNITED STATES
                Author notes

                Competing Interests: The authors have declared no competing interests exist.

                • Conceptualization: SM CS HR.

                • Data curation: SM CS XH EC.

                • Formal analysis: SM CS XH EC.

                • Funding acquisition: HR CS.

                • Investigation: SM XE EC CS.

                • Methodology: SM HR AT NT CS EC XH.

                • Project administration: HR CS.

                • Resources: HR CS AT NT.

                • Supervision: HR CS.

                • Visualization: SM XH CS HR.

                • Writing – original draft: SM.

                • Writing – review & editing: SM HR CS XH EC AT NT.

                Article
                PONE-D-16-22919
                10.1371/journal.pone.0171672
                5308786
                28196086
                fb8fb56b-7ed0-42e9-b8bf-f7acb0f681a6
                © 2017 Moran-Ramos et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 June 2016
                : 24 January 2017
                Page count
                Figures: 10, Tables: 4, Pages: 23
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: DK41004
                Award Recipient :
                Funded by: Conacyt
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100005825, National Institute of Food and Agriculture;
                Award ID: Hatch Project 1005945
                Award Recipient :
                This work was supported by the National Institute of Health DK41004 (HR); USDA National Institute of Food and Agriculture Hatch Project 1005945 (CS); Conacyt Scholarship Mexico (S M-R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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