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      Anti-obesity effects of Spirulina platensis protein hydrolysate by modulating brain-liver axis in high-fat diet fed mice

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          Abstract

          Spirulina platensis is a blue-green algae with potential anti-obesity effects. In this study, the anti-obesity effects of whole Spirulina platensis (WSP), Spirulina platensis protein (SPP) and Spirulina platensis protein hydrolysate (SPPH) were compared in high-fat diet fed mice, and the potential acting mechanism of SPPH was also investigated. Totally, SPPH exhibited good anti-obesity effects (reducing 39.8%±9.7% of body weight), lowering 23.8%±1.6% of serum glucose, decreasing 20.8%±1.4% of total cholesterol, while positive drug Simvastatin had the corresponding values: 8.3%±4.6%, 24.8%±1.9% and -2.1%±0.2%, respectively. Subsequently, PCR array was used to conduct gene expression analysis in brain and liver tissues of SPPH-treated mice, which displayed distinctly different expression pattern. The most markedly changed genes included: Acadm (-34.7 fold), Gcg (2.5 fold), Adra2b (2 fold) and Ghsr (2 fold) in brain; Retn (39 fold), Fabp4 (15.5 fold), Ppard (6 fold) and Slc27a1 (5.4 fold) in liver. Further network analysis demonstrated that the significantly expressed genes in brain and liver tissues were mapped into an interacting network, suggesting a modulatory effect on brain-liver axis, major pathways were involved in the axis: PPAR, adipocytokine, AMPK, non-alcoholic fatty liver disease and MAPK. This study showed that Spirulina platensis protein hydrolysate possessed anti-obesity effect in mice.

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          Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production.

          Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.
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            Marine Algae as a Potential Source for Anti-Obesity Agents

            Obesity is a major epidemic that poses a worldwide threat to human health, as it is also associated with metabolic syndrome, type 2 diabetes and cardiovascular disease. Therapeutic intervention through weight loss drugs, accompanied by diet and exercise, is one of the options for the treatment and management of obesity. However, the only approved anti-obesity drug currently available in the market is orlistat, a synthetic inhibitor of pancreatic lipase. Other anti-obesity drugs are still being evaluated at different stages of clinical trials, while some have been withdrawn due to their severe adverse effects. Thus, there is a need to look for new anti-obesity agents, especially from biological sources. Marine algae, especially seaweeds are a promising source of anti-obesity agents. Four major bioactive compounds from seaweeds which have the potential as anti-obesity agents are fucoxanthin, alginates, fucoidans and phlorotannins. The anti-obesity effects of such compounds are due to several mechanisms, which include the inhibition of lipid absorption and metabolism (e.g., fucoxanthin and fucoidans), effect on satiety feeling (e.g., alginates), and inhibition of adipocyte differentiation (e.g., fucoxanthin). Further studies, especially testing bioactive compounds in long-term human trials are required before any new anti-obesity drugs based on algal products can be developed.
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              Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice.

              Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo.
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                Author and article information

                Contributors
                Role: Investigation
                Role: Investigation
                Role: Project administrationRole: Validation
                Role: Data curationRole: Resources
                Role: ConceptualizationRole: Resources
                Role: ConceptualizationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: SupervisionRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 June 2019
                2019
                : 14
                : 6
                : e0218543
                Affiliations
                [1 ] College of Food Science and Engineering, South China University of Technology, Guangzhou, China
                [2 ] Guangzhou Institute for Food and Drug Control, Guangzhou, China
                [3 ] Zhongci Health Care Products Technology Development Co. Ltd, Guangzhou, China
                [4 ] Guangzhou Honsea Industry Co. Ltd, Guangzhou, China
                University of Southern Queensland, AUSTRALIA
                Author notes

                Competing Interests: The commercial affiliations of Zhongci Health Care Products Technology Development Co. Ltd, Guangzhou, China and Guangzhou Honsea Industry Co. Ltd, Guangzhou, China do not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0001-9870-0686
                Article
                PONE-D-19-00520
                10.1371/journal.pone.0218543
                6586325
                31220177
                cede2660-5357-47b9-ba6c-ff2f3ffac424
                © 2019 Zhao 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 January 2019
                : 4 June 2019
                Page count
                Figures: 3, Tables: 2, Pages: 14
                Funding
                The authors received no specific funding for this work. The commercial affiliations Zhongci Health Care Products Technology Development Co. Ltd, Guangzhou, China and Guangzhou Honsea Industry Co. Ltd, Guangzhou, China did not provide funding for this project. The commercial affiliations provided support in the form of salaries for authors [Chunchen Liu, Xuesong Zhou], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors Chunchen Liu and Xuesong Zhou from the two affiliations made contributions to the manuscript, already articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Biology and Life Sciences
                Nutrition
                Diet
                Medicine and Health Sciences
                Nutrition
                Diet
                Biology and Life Sciences
                Genetics
                Gene Expression
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Biochemistry
                Lipids
                Cholesterol
                Biology and life sciences
                Cell biology
                Signal transduction
                Cell signaling
                PPAR signaling
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fats
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

                Uncategorized
                Uncategorized

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