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      Effect of Forskolin on Body Weight, Glucose Metabolism and Adipocyte Size of Diet-Induced Obesity in Mice

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          Abstract

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          Obesity has become a global pandemic involving an increase in the amount and size of fat cells in the body. Obesity is highly associated with insulin resistance and type 2 diabetes. Several medicinal plants have been reported to be useful in the prevention of obesity. Forskolin, a bioactive compound of Coleus forskohlii, can promote lipolysis in mature adipocytes. However, the effect of forskolin on body weight, glucose metabolism and adipocyte size of diet-induced obesity is still rarely investigated. In this study, the effects of forskolin on the high-fat diet-induced obese model were evaluated. Results showed that forskolin administration improves glucose metabolism and reduces fat cell diameter in the high-fat diet-fed mice. Forskolin also suppresses adipocyte differentiation of murine mesenchymal stem cells.

          Abstract

          The purpose of this study was to investigate the effects of forskolin on body weight, glucose metabolism and fat cell diameter in high-fat diet-induced obese mice. Four-week-old male mice (C57BL/6) were randomly assigned to 1 of 3 treatment groups: a high-fat diet plus 5% dimethyl sulfoxide (vehicle), high-fat diet plus 2 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide) and high-fat diet plus 4 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide). Forskolin or dimethyl sulfoxide was administered intraperitoneally every two days. The results indicated that no significant difference was observed in the body weight, feed intake and serum lipid parameters among groups at 20 weeks of age. The blood glucose levels were significantly reduced in the groups treated with 2 mg/kg of forskolin before glucose tolerance test. Forskolin administration linearly decreased blood glucose levels of high-fat diet-fed mice at 90 min and total area under curve (AUC) after insulin tolerance test. The subcutaneous adipocyte diameter was significantly reduced in the groups treated with 2 mg/kg of forskolin. Forskolin administration linearly reduced the gonadal adipocyte diameter of high-fat diet-fed mice. Forskolin significantly reduced the differentiation of murine mesenchymal stem cells into adipocytes and this was accompanied by a decrease in intracellular triglyceride content and an increase in glycerol concentration in the culture medium. The subcutaneous adipocyte diameter, gonadal adipocyte diameter and total AUC of insulin tolerance test were moderately negatively correlated with the concentration of forskolin in the high-fat diet-induced obese model. These results demonstrate that forskolin can regulate glucose metabolism and reduce fat cell diameter of high-fat diet-fed mice and inhibit the adipocyte differentiation of murine mesenchymal stem cells.

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          Most cited references25

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          Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index.

          Although international interest in classifying subject health status according to adiposity is increasing, no accepted published ranges of percentage body fat currently exist. Empirically identified limits, population percentiles, and z scores have all been suggested as means of setting percentage body fat guidelines, although each has major limitations. The aim of this study was to examine a potential new approach for developing percentage body fat ranges. The approach taken was to link healthy body mass index (BMI; in kg/m(2)) guidelines established by the National Institutes of Health and the World Health Organization with predicted percentage body fat. Body fat was measured in subjects from 3 ethnic groups (white, African American, and Asian) who were screened and evaluated at 3 universities [Cambridge (United Kingdom), Columbia (United States), and Jikei (Japan)] with use of reference body-composition methods [4-compartment model (4C) at 2 laboratories and dual-energy X-ray absorptiometry (DXA) at all 3 laboratories]. Percentage body fat prediction equations were developed based on BMI and other independent variables. A convenient sample of 1626 adults with BMIs or =25), and obesity (> or =30). This proposed approach and initial findings provide the groundwork and stimulus for establishing international healthy body fat ranges.
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            The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies.

            The objectives of this meta-analysis were to examine the magnitude of the relative risk (RR) of developing type 2 diabetes for overweight and obese populations, compared to those with normal weight, and to determine causes of the variation in RR between various cohort studies. The magnitude of the RR was analyzed by combining 18 prospective cohort studies that matched defined criteria. The variance in RR between studies was explored. The overall RR of diabetes for obese persons compared to those with normal weight was 7.19, 95% CI: 5.74, 9.00 and for overweight was 2.99, 95% CI: 2.42, 3.72. The variation in RR among studies was explored and it was found that the effect of heterogeneity was highly related with sample size, method of assessment of body mass index (BMI) and method of ascertainment of type 2 diabetes. By combining only cohort studies with more than 400 cases of incident diabetes (>median), adjusted by at least three main confounding variables (age, family history of type 2 diabetes, physical activity), measured BMI, and diabetes determined by clinical diagnosis, the RR was 7.28, 95% CI: 6.47, 8.28 for obesity and 2.92, 95% CI: 2.57, 3.32 for overweight. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
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              Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans

              Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Animals (Basel)
                Animals (Basel)
                animals
                Animals : an Open Access Journal from MDPI
                MDPI
                2076-2615
                01 March 2021
                March 2021
                : 11
                : 3
                : 645
                Affiliations
                [1 ]Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; 3311qq44@ 123456gmail.com (J.-Y.C.); yhcheng@ 123456niu.edu.tw (Y.-H.C.)
                [2 ]Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan; sypeng@ 123456mail.npust.edu.tw
                [3 ]School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; itlee0128@ 123456tmu.edu.tw
                Author notes
                [* ]Correspondence: yuyh@ 123456niu.edu.tw ; Tel.: +886-3-931-7716
                Author information
                https://orcid.org/0000-0001-6009-6006
                https://orcid.org/0000-0001-9629-8478
                Article
                animals-11-00645
                10.3390/ani11030645
                8000574
                62a78494-2a8f-4e37-8d7e-181787bf13aa
                © 2021 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
                : 08 February 2021
                : 24 February 2021
                Categories
                Article

                adipocyte,forskolin,glucose,mesenchymal stem cell,mouse,obesity
                adipocyte, forskolin, glucose, mesenchymal stem cell, mouse, obesity

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