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      Antiobesity Effects of Gentiana lutea Extract on 3T3-L1 Preadipocytes and a High-Fat Diet-Induced Mouse Model

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          Abstract

          Obesity is one of the most common metabolic diseases resulting in metabolic syndrome. In this study, we investigated the antiobesity effect of Gentiana lutea L. (GL) extract on 3T3-L1 preadipocytes and a high-fat-diet (HFD)-induced mouse model. For the induction of preadipocytes into adipocytes, 3T3-L1 cells were induced by treatment with 0.5 mM 3-isobutyl-1-methylxanthine, 1 mM dexamethasone, and 1 μg/mL insulin. Adipogenesis was assessed based on the messenger ribonucleic acid expression of adipogenic-inducing genes (adiponectin ( Adipoq), CCAAT/enhancer-binding protein alpha ( Cebpa), and glucose transporter type 4 ( Slc2a4)) and lipid accumulation in the differentiated adipocytes was visualized by Oil Red O staining. In vivo, obese mice were induced with HFD and coadministered with 100 or 200 mg/kg/day of GL extract for 12 weeks. GL extract treatment inhibited adipocyte differentiation by downregulating the expression of adipogenic-related genes in 3T3-L1 cells. In the obese mouse model, GL extract prevented HFD-induced weight gain, fatty hepatocyte deposition, and adipocyte size by decreasing the secretion of leptin and insulin. In conclusion, GL extract shows antiobesity effects in vitro and in vivo, suggesting that this extract can be beneficial in the prevention of obesity.

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          Most cited references26

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          Long-term drug treatment for obesity: a systematic and clinical review.

          Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone. To conduct a systematic review of medications currently approved in the United States for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice. A PubMed search from inception through September 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently approved obesity medications lasting at least 1 year that had a primary or secondary outcome of body weight change, included at least 50 participants per group, reported at least 50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed. Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine plus topiramate-extended release at 1 year. The proportion of patients achieving clinically meaningful (at least 5%) weight loss ranges from 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for top-dose phentermine plus topiramate-extended release. All 3 medications produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy. Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss of at least 5%, clinicians can decrease their patients' exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit.
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            Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue.

            To gain insight into the molecular pathogenesis of obesity and specifically the role of nutrient partitioning in the development of obesity, we overexpressed the insulin-responsive glucose transporter (GLUT4) in transgenic mice under the control of the fat-specific aP2 fatty acid-binding protein promoter/enhancer. Two lines of transgenic mice were generated, which overexpressed GLUT4 6-9-fold in white fat and 3-5-fold in brown fat with no overexpression in other tissues. In vivo glucose tolerance was enhanced in transgenic mice. In isolated epididymal, parametrial, and subcutaneous adipose cells from transgenic mice, basal glucose transport was 20-34-fold greater than in nontransgenic littermates. Insulin-stimulated glucose transport was 2-4-fold greater in cells from transgenic mice. Total body lipid was increased 2-3-fold in transgenic mice overexpressing GLUT4 in fat. Surprisingly, fat cell size was unaltered and fat cell number was increased > 2-fold. This is the first animal model in which increased fat mass results solely from adipocyte hyperplasia and it will be a valuable model for understanding the mechanisms responsible for fat cell replication and/or differentiation in vivo.
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              Use of high-fat diets to study rodent obesity as a model of human obesity

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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                25 May 2020
                May 2020
                : 25
                : 10
                : 2453
                Affiliations
                [1 ]Department of Medical Genetics, Graduate School of Medicine, Ajou University, Suwon 16499, Korea; jude0815@ 123456hotmail.com (E.P.); dangsunsang@ 123456naver.com (C.G.L.)
                [2 ]Department of Biomedical Sciences, Graduate School of Medicine, Ajou University, Suwon 16499, Korea
                [3 ]Nine B Company, Daejeon 34121, Korea; kjh_nineb@ 123456naver.com (J.K.); snsnans@ 123456naver.com (S.Y.); ji.ae.kim@ 123456daum.net (J.A.K.)
                [4 ]Natural Product Research Team, Biocenter, Gyeonggido Business and Science Accelerator, Suwon 16229, Korea; cwchoi78@ 123456gmail.com
                Author notes
                [* ]Correspondence: jeongsy@ 123456ajou.ac.kr ; Tel.: +82-31-219-4520; Fax: +82-31-219-4521
                Author information
                https://orcid.org/0000-0002-1928-5531
                https://orcid.org/0000-0002-0625-3530
                Article
                molecules-25-02453
                10.3390/molecules25102453
                7288051
                32466183
                40c3e070-51b8-4c5a-89dc-4887301f9435
                © 2020 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
                : 21 April 2020
                : 21 May 2020
                Categories
                Article

                gentiana lutea l,obesity,3t3-l1 cell,high fat diet,adipogenesis

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