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      Dietary flaxseed oil rich in omega-3 suppresses severity of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in rats

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          Abstract

          Background

          Type 2 diabetes mellitus (T2DM) is closely associated with hyperglycemia, abnormal lipid profiles, chronic low-grade inflammation and gut dysbiosis. Dietary intervention plays a crucial role in the control of diabetes. Flaxseed oil (FO), a plant-derived omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), is rich in α-linolenic acid (ALA) which has been proved to benefit for chronic metabolic disease. However, the exact effects of dietary FO on T2DM remains largely unclear.

          Methods

          In the present study, SD rats were randomly allocated into four groups: pair-fed (PF) with corn oil (CO) group (PF/CO); DM with CO group (DM/CO); PF with FO group (PF/FO); DM with FO group (DM/FO). A diabetic rat model was generated by a single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NA). After 5 weeks of intervention, rats were euthanized and associated indications were investigated.

          Results

          Dietary FO significantly reduced fasting blood glucose (FBG), glycated hemoglobin (GHb), blood lipid, plasma lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-17A and malondialdehyde (MDA), compared to control group, respectively. Moreover, body mass (BM) and superoxide dismutase (SOD) in DM/FO group were dramatically increased respectively, compared with those in DM/CO group. But insulin (INS) and homeostasis model assessment of insulin resistance (HOMA-IR) remained no significant difference between DM/CO group and DM/FO group. Sequencing analysis of gut microbiota showed a reduction in the relative abundance of Firmicutes and Blautia, as well as a reduction in the ratio of Bacteroidetes-Firmicutes in DM/FO group compared to DM/CO group. An elevation in the relative abundance of Bacteroidetes and Alistipes were detected in DM/FO group. Acetic acid, propionic acid and butyric acid belonging to short chain fatty acids (SCFAs) as gut microbiota metabolites, were dramatically increased after FO intervention. Correlation analysis revealed that the relative abundance of Firmicutes and Blautia were positively correlated with IL-1β, TNF-α, IL-6, IL-17A or LPS, respectively. Additionally, Bacteroidetes and Alistipes were negatively correlated with LPS.

          Conclusions

          Taken together, dietary FO ameliorated T2DM via suppressing inflammation and modulating gut microbiota, which may potentially contribute to dietary control of diabetes.

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          Most cited references34

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          Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).

          Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects. We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (S(I)) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), S(I), and fasting insulin and proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were consistent among the 3 ethnic groups of the IRAS. There was a linear increase in CRP levels with an increase in the number of metabolic disorders. Body mass index, systolic blood pressure, and S(I) were related to CRP levels in a multivariate linear regression model. We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to S(I). These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment strategies in healthy individuals with features of IRS.
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            Impact of Omega-3 Fatty Acids on the Gut Microbiota

            Long-term dietary habits play a crucial role in creating a host-specific gut microbiota community in humans. Despite the many publications about the effects of carbohydrates (prebiotic fibers), the impact of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota is less well defined. The few studies completed in adults showed some common changes in the gut microbiota after omega-3 PUFA supplementation. In particular, a decrease in Faecalibacterium, often associated with an increase in the Bacteroidetes and butyrate-producing bacteria belonging to the Lachnospiraceae family, has been observed. Coincidentally, a dysbiosis of these taxa is found in patients with inflammatory bowel disease. Omega-3 PUFAs can exert a positive action by reverting the microbiota composition in these diseases, and increase the production of anti-inflammatory compounds, like short-chain fatty acids. In addition, accumulating evidence in animal model studies indicates that the interplay between gut microbiota, omega-3 fatty acids, and immunity helps to maintain the intestinal wall integrity and interacts with host immune cells. Finally, human and animal studies have highlighted the ability of omega-3 PUFAs to influence the gut–brain axis, acting through gut microbiota composition. From these findings, the importance of the omega-3 connection to the microbiota emerges, encouraging further studies.
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              Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect.

              Metformin is an oral hypoglycemic agent which is most widely used as first-line therapy for type 2 diabetes. Metformin improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscle. Metformin also has been shown to reduce cardiovascular events in randomized controlled trials; however, the underlying mechanism remains to be established. Recent preclinical and clinical studies have suggested that metformin not only improves chronic inflammation through the improvement of metabolic parameters such as hyperglycemia, insulin resistance and atherogenic dyslipidemia, but also has a direct anti-inflammatory action. Studies have suggested that metformin suppresses inflammatory response by inhibition of nuclear factor κB (NFκB) via AMP-activated protein kinase (AMPK)-dependent and independent pathways. This review summarizes the basic and clinical evidence of the anti-inflammatory action of metformin and discusses its clinical implication.
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                Author and article information

                Contributors
                1431082928@qq.com
                shaliping1998@126.com
                350944254@qq.com
                742927380@qq.com
                2561466083@qq.com
                775739071@qq.com
                hanner752003@163.com
                dongxy1998@163.com
                Ldong683@163.com
                zxx1216@163.com
                wanghaograduate@126.com
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                7 February 2020
                7 February 2020
                2020
                : 19
                : 20
                Affiliations
                [1 ]GRID grid.412194.b, ISNI 0000 0004 1761 9803, Department of Pathogenic Biology and Medical Immunology, School of Basic Medical Sciences, , Ningxia Medical University, ; Yinchuan, 750004 Ningxia China
                [2 ]GRID grid.413385.8, Endocrinology Department, , General Hospital of Ningxia Medical University, ; Yinchuan, 750004 Ningxia China
                [3 ]GRID grid.469519.6, ISNI 0000 0004 1758 070X, Endocrinology Department, , People’s Hospital of Ningxia Hui Autonomous Region, ; Yinchuan, 750002 Ningxia China
                [4 ]GRID grid.412194.b, ISNI 0000 0004 1761 9803, Clinical Medical College, , Ningxia Medical University, ; Yinchuan, 750004 Ningxia China
                [5 ]GRID grid.412194.b, ISNI 0000 0004 1761 9803, College of Traditional Chinese Medicine, , Ningxia Medical University, ; Yinchuan, 750004 Ningxia China
                Author information
                http://orcid.org/0000-0002-5776-8681
                Article
                1167
                10.1186/s12944-019-1167-4
                7006389
                32028957
                fb94fc9f-51aa-4761-b96a-8b2d976a7410
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 August 2019
                : 9 December 2019
                Funding
                Funded by: the research and development plan of the 13th five-year plan of Ningxia autonomous region
                Award ID: 2016BZ02
                Funded by: the first class discipline project in College of Traditional Chinese Medicine in Ningxia Medical University, China
                Award ID: NXYLXK2017A06
                Award Recipient :
                Funded by: Ningxia High School first-class Disciplines (West China first-class Disciplines Basic Medical Sciences at Ningxia Medical University), China
                Award ID: NXYLXK2017B07
                Award Recipient :
                Funded by: the National Key Research and Development Program of China
                Award ID: 2016YFD0400605
                Award Recipient :
                Funded by: the Construction of Clinical Research Platform for Gut Microecology and Endocrine Diseases, China, the Research Project of Ningxia Medical University, China
                Award ID: XT2018007
                Award Recipient :
                Funded by: the first class discipline construction project in Colleges and Universities of Ningxia, China
                Award ID: NXYLXK2017A05
                Award Recipient :
                Funded by: the research project of Ningxia Medical Univeristy
                Award ID: XT2018007
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Biochemistry
                flaxseed oil,t2dm,anti-inflammation,gut microbiota
                Biochemistry
                flaxseed oil, t2dm, anti-inflammation, gut microbiota

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