Kyle Miller, Sarah Carpinelli, Maxwell Rubin, John Ahlert, Aaron Kubinski, Brendan Van Iten, Kendra Sy, Bryan Lunt, Katerina Meassick, Stephen Ames, Emma Smith, Chaheyla R St Aubin, Layla Al-Nakkash
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Genistein concentration was 600 mg genistein/kg diet. Exercise comprised of moderate intensity treadmill running (150 min per week). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum cytokine assays were performed.</p><p><strong>Results: </strong>Basal I<sub>sc</sub> was significantly decreased (by 70%, P<0.05) in HFS females and males versus leans. This decrease was partially mitigated by exercise in both sexes. In females, the HFS-induced decrease in I<sub>sc</sub> was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males this was due to a significant loss of Na/K-ATPase, K<sub>Ca</sub> and NKCC1 expression (indicating sex-dependent mechanisms). Exercise mitigated most of the loss of I<sub>sc</sub> in both sexes. Our data suggested that A2BR levels were dysregulated in HFS fed mice and that concomitant treatment with Gen or Gen+Ex prevented this disruption in females only. Inflammatory state was associated with body weight changes.</p><p><strong>Conclusion: </strong>Our data suggests that the reduced basal jejunal I<sub>sc</sub> in HFS mice is attributed to sex-dependent mechanisms and while exercise partially mitigated this, it's mechanism of action was unclear. Improved understanding of Western diet induced intestinal dysfunctions may allow for the development of novel drug targets to treat gastrointestinal disturbances in diabetic obesity.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"315-330"},"PeriodicalIF":2.5000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High Fat High Sugar Diet Reduces Small Intestinal Secretion by Sex-Dependent Mechanisms.\",\"authors\":\"Kyle Miller, Sarah Carpinelli, Maxwell Rubin, John Ahlert, Aaron Kubinski, Brendan Van Iten, Kendra Sy, Bryan Lunt, Katerina Meassick, Stephen Ames, Emma Smith, Chaheyla R St Aubin, Layla Al-Nakkash\",\"doi\":\"10.33594/000000659\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aims: </strong>The goal of this study was to determine the influence of high-fat high-sugar diet (Western diet) on intestinal function and subsequently to determine if there were any beneficial effects of exercise, genistein (a naturally occurring phytoestrogen) or both, on the intestine.</p><p><strong>Methods: </strong>We measured transepithelial short circuit current (I<sub>sc</sub>), across freshly isolated segments of jejunum from male and female C57Bl/6J mice randomly assigned to one of the following groups for the 12-week study duration: high-fat high-sugar diet (HFS), HFS with genistein (Gen), HFS with exercise (Ex), or HFS with both genistein and exercise (Gen+Ex) and compared them to lean controls. Genistein concentration was 600 mg genistein/kg diet. Exercise comprised of moderate intensity treadmill running (150 min per week). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum cytokine assays were performed.</p><p><strong>Results: </strong>Basal I<sub>sc</sub> was significantly decreased (by 70%, P<0.05) in HFS females and males versus leans. This decrease was partially mitigated by exercise in both sexes. In females, the HFS-induced decrease in I<sub>sc</sub> was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males this was due to a significant loss of Na/K-ATPase, K<sub>Ca</sub> and NKCC1 expression (indicating sex-dependent mechanisms). Exercise mitigated most of the loss of I<sub>sc</sub> in both sexes. Our data suggested that A2BR levels were dysregulated in HFS fed mice and that concomitant treatment with Gen or Gen+Ex prevented this disruption in females only. Inflammatory state was associated with body weight changes.</p><p><strong>Conclusion: </strong>Our data suggests that the reduced basal jejunal I<sub>sc</sub> in HFS mice is attributed to sex-dependent mechanisms and while exercise partially mitigated this, it's mechanism of action was unclear. 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引用次数: 0
摘要
背景/目的:本研究的目的是确定高脂肪高糖饮食(西方饮食)对肠道功能的影响，随后确定运动、染料木素(一种天然存在的植物雌激素)或两者对肠道是否有任何有益的影响。方法:我们测量了刚分离的雄性和雌性C57Bl/6J小鼠空肠的经上皮短路电流(Isc)，这些小鼠被随机分为以下组，在12周的研究期间:高脂肪高糖饮食(HFS)，高脂肪高糖饮食(Gen)，高脂肪高糖饮食(Gen)，高脂肪高糖饮食(Gen)，运动高脂肪高糖饮食(Ex)，或高脂肪高糖饮食和运动高脂肪高糖饮食(Gen)，运动高脂肪高糖饮食(Ex)，或高脂肪高脂肪高糖饮食和运动高脂肪高糖饮食(Gen+Ex)，并将它们与瘦对照组进行比较。染料木素浓度为600 mg /kg日粮。运动包括中等强度的跑步机跑步(每周150分钟)。研究结束后，冷冻空肠各节段，western blot检测参与分泌和吸收功能以及衰老的关键蛋白。观察肠道形态。进行血清细胞因子测定。结果:基础Isc显著降低(70%，Psc归因于CLC2, NKCC1和CFTR表达的显著丧失，而在男性中，这是由于Na/ k - atp酶，KCa和NKCC1表达的显著丧失(表明性别依赖机制)。无论男女，运动都能减轻大部分Isc的损失。我们的数据表明，HFS喂养的小鼠中A2BR水平失调，而Gen或Gen+Ex的联合治疗仅在雌性小鼠中防止了这种失调。炎症状态与体重变化有关。结论:我们的数据表明，HFS小鼠基底空肠Isc的减少归因于性别依赖机制，虽然运动部分减轻了这一点，但其作用机制尚不清楚。改善对西方饮食引起的肠道功能障碍的理解可能允许开发新的药物靶点来治疗糖尿病性肥胖的胃肠道紊乱。
High Fat High Sugar Diet Reduces Small Intestinal Secretion by Sex-Dependent Mechanisms.
Background/aims: The goal of this study was to determine the influence of high-fat high-sugar diet (Western diet) on intestinal function and subsequently to determine if there were any beneficial effects of exercise, genistein (a naturally occurring phytoestrogen) or both, on the intestine.
Methods: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from male and female C57Bl/6J mice randomly assigned to one of the following groups for the 12-week study duration: high-fat high-sugar diet (HFS), HFS with genistein (Gen), HFS with exercise (Ex), or HFS with both genistein and exercise (Gen+Ex) and compared them to lean controls. Genistein concentration was 600 mg genistein/kg diet. Exercise comprised of moderate intensity treadmill running (150 min per week). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum cytokine assays were performed.
Results: Basal Isc was significantly decreased (by 70%, P<0.05) in HFS females and males versus leans. This decrease was partially mitigated by exercise in both sexes. In females, the HFS-induced decrease in Isc was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males this was due to a significant loss of Na/K-ATPase, KCa and NKCC1 expression (indicating sex-dependent mechanisms). Exercise mitigated most of the loss of Isc in both sexes. Our data suggested that A2BR levels were dysregulated in HFS fed mice and that concomitant treatment with Gen or Gen+Ex prevented this disruption in females only. Inflammatory state was associated with body weight changes.
Conclusion: Our data suggests that the reduced basal jejunal Isc in HFS mice is attributed to sex-dependent mechanisms and while exercise partially mitigated this, it's mechanism of action was unclear. Improved understanding of Western diet induced intestinal dysfunctions may allow for the development of novel drug targets to treat gastrointestinal disturbances in diabetic obesity.
期刊介绍：
Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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