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      Lactobacillus plantarum Strain Ln4 Attenuates Diet-Induced Obesity, Insulin Resistance, and Changes in Hepatic mRNA Levels Associated with Glucose and Lipid Metabolism

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          Abstract

          The prevalence of obesity and associated metabolic disorders, including diabetes and cardiovascular disease, is rapidly becoming a severe global health problem. Recent reports have suggested that the alteration of the gut ecosystem through the consumption of probiotics and fermented foods, such as yogurt and Kimchi, can significantly impact obesity and Type 2 diabetes (T2D)-related biomarkers. In this study, we screened over 400 strains of lactic acid bacteria (LAB) that were isolated from fermented foods to identify potent anti-obesogenic and diabetic probiotics in vitro. Of the strains tested, Lactobacillus plantarum Ln4 (Ln4), which was obtained from napa cabbage kimchi, significantly reduced lipid accumulation and stimulated glucose uptake in 3T3-L1 adipocytes. Oral administration of Ln4 reduced weight gain and epididymal fat mass in mice fed on a high-fat diet (HFD). Total plasma triglyceride level was significantly lower in mice that were treated Ln4 as compared with mice fed HFD. The protein levels of adipokines such as C-reactive protein (CRP), insulin-like growth factor binding proteins-3 (IGFBP-3), and monocyte chemoattractant protein-1 (MCP-1) decreased in white adipose tissues of Ln4-treated mice. Furthermore, these mice exhibited a significant reduction of insulin resistance index (HOMA-IR) and the improvement of glucose tolerance (OGTT) and insulin response (ITT) following Ln4 administration. This was associated with changes in several hepatic gene expressions (increased mRNA levels of IRS2, Akt2, AMPK, LPL, and reduced CD36) that regulate glucose and lipid metabolism. Taken together, these results indicate that in vitro and in vivo Ln4 treatment attenuates diet-induced obesity and T2D biomarkers, highlighting the potential of Ln4 as a therapeutic probiotic agent for metabolic disorders.

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          MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.

          Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein-1 (MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content. Furthermore, insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice compared with WT animals. Finally, acute expression of a dominant-negative mutant of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a high-fat diet. These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice.
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            Overview of epidemiology and contribution of obesity to cardiovascular disease.

            The prevalence of obesity has increased worldwide and is a source of concern since the negative consequences of obesity start as early as in childhood. The most commonly used anthropometric tool to assess relative weight and classify obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality. Such an inverse relationship fuels a controversy in the literature, named the 'obesity paradox', which associates better survival and fewer cardiovascular (CV) events in patients with elevated BMI afflicted with chronic diseases compared to non-obese patients. However, BMI cannot make the distinction between an elevated body weight due to high levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is more frequently associated with metabolic abnormalities than a high level of lean body mass. Another explanation for the paradox is the absence of control for major individual differences in regional BF distribution. Adipose tissue is now considered as a key organ regarding the fate of excess dietary lipids, which may determine whether or not body homeostasis will be maintained (metabolically healthy obesity) or a state of inflammation/insulin resistance will be produced, with deleterious CV consequences. Obesity, particularly visceral obesity, also induces a variety of structural adaptations/alterations in CV structure/function. Adipose tissue can now be considered as an endocrine organ orchestrating crucial interactions with vital organs and tissues such as the brain, the liver, the skeletal muscle, the heart and blood vessels themselves. Thus, the evidence reviewed in this paper suggests that adipose tissue quality/function is as important, if not more so, than its amount in determining the overall health and CV risks of overweight/obesity. © 2013.
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              Probiotics and their fermented food products are beneficial for health.

              Probiotics are usually defined as microbial food supplements with beneficial effects on the consumers. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks or other fermented foods. Some of the beneficial effect of lactic acid bacteria consumption include: (i) improving intestinal tract health; (ii) enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients; (iii) reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals; and (iv) reducing risk of certain cancers. The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase. Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed. Recent scientific investigation has supported the important role of probiotics as a part of a healthy diet for human as well as for animals and may be an avenue to provide a safe, cost effective, and 'natural' approach that adds a barrier against microbial infection. This paper presents a review of probiotics in health maintenance and disease prevention.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                19 May 2018
                May 2018
                : 10
                : 5
                : 643
                Affiliations
                [1 ]Research group of Traditional Food, Korea Food Research Institute, Wanju 55365, Korea; jarasasa2@ 123456gmail.com
                [2 ]Research Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju 55365, Korea; sylee09@ 123456kfri.re.kr
                [3 ]Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Korea; lnk11@ 123456konkuk.ac.kr (N.-K.L.); hdpaik@ 123456konkuk.ac.kr (H.-D.P.)
                [4 ]Research Group of Healthcare, Korea Food Research Institute, Wanju 55365, Korea
                Author notes
                [* ]Correspondence: ejlee@ 123456kfri.re.kr (E.L.); silim@ 123456kfri.re.kr (S.-I.L.); Tel.: +063-219-9413 (E.L.); +063-219-9277 (S.-I.L.)
                [†]

                These authors have contributed equally to this work.

                Article
                nutrients-10-00643
                10.3390/nu10050643
                5986522
                29783731
                c46ebfdc-7cb3-44a0-9416-251b167ac46d
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 March 2018
                : 17 May 2018
                Categories
                Article

                Nutrition & Dietetics
                lactobacillus plantarum ln4,obesity,high fat diet,insulin resistance,metabolic disorder,insulin signaling

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