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Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice

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      Abstract

      Objective Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity.Materials and methods NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples.Results All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent.Conclusion In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress. Arch Endocrinol Metab. 2015;59(3):202-9

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      Lipotoxicity: when tissues overeat.

      This review will provide the reader with an update on our understanding of the adverse effects of fatty acid accumulation in non-adipose tissues, a phenomenon known as lipotoxicity. Recent studies will be reviewed. Cellular mechanisms involved in the lipotoxic response will be discussed. Physiologic responses to lipid overload and therapeutic approaches to decreasing lipid accumulation will be discussed, as they add to our understanding of important pathophysiologic mechanisms. Excess lipid accumulation in non-adipose tissues may arise in the setting of high plasma free fatty acids or triglycerides. Alternatively, lipid overload results from mismatch between free fatty acid import and utilization. Evidence from human studies and animal models suggests that lipid accumulation in the heart, skeletal muscle, pancreas, liver, and kidney play an important role in the pathogenesis of heart failure, obesity and diabetes. Excess free fatty acids may impair normal cell signaling, causing cellular dysfunction. In some circumstances, excess free fatty acids induce apoptotic cell death. Recent studies provide clues regarding the cellular mechanisms that determine whether excess lipid accumulation is well tolerated or cytotoxic. Critical in this process are physiologic mechanisms for directing excess free fatty acids to specific tissues as well as cellular mechanisms for channeling excess fatty acid to particular metabolic fates. Insight into these mechanisms may contribute to the development of more effective therapies for common human disorders in which lipotoxicity contributes to pathogenesis.
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        Adipokines – removing road blocks to obesity and diabetes therapy☆

        Prevention of obesity and therapeutic weight loss interventions have provided only limited long term success. Therefore there is an urgent need to develop novel pharmacological treatment strategies, which target mechanisms underlying positive energy balance, excessive fat accumulation and adverse fat distribution. Adipokines may have potential for future pharmacological treatment strategies of obesity and metabolic diseases, because they are involved in the regulation of appetite and satiety, energy expenditure, endothelial function, blood pressure, insulin sensitivity, adipogenesis, fat distribution and insulin secretion and others. There are important road blocks on the way from an adipokine candidate to the clinical use a therapeutic compound. Such road blocks include an incomplete understanding of the mechanism of action, resistance to a specific adipokine, side effects of the adipokine and others. This review focuses on the potential of selected adipokines as therapeutic tools or targets and discusses important road blocks, which currently prevent their clinical use.
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          Exploring Pharmacological Significance of Chalcone Scaffold: A Review

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            Author and article information

            Affiliations
            [1 ] Islamic Azad University Iran
            [2 ] Tehran University of Medical Sciences Iran
            [3 ] Shahid Beheshti University of Medical Science Iran
            [4 ] Tehran University of Medical Sciences Iran
            [5 ] Tehran University of Medical Sciences Iran
            Contributors
            Role: ND
            Role: ND
            Role: ND
            Role: ND
            Role: ND
            Journal
            aem
            Archives of Endocrinology and Metabolism
            Arch. Endocrinol. Metab.
            Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo )
            2359-4292
            June 2015
            : 59
            : 3
            : 202-209
            S2359-39972015000300202 10.1590/2359-3997000000038

            http://creativecommons.org/licenses/by/4.0/

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            Product Information: SciELO Brazil
            Categories
            ENDOCRINOLOGY & METABOLISM
            MEDICINE, GENERAL & INTERNAL

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