力量和体重训练可以控制肥胖个体的糖尿病 Strength and weight training can control diabetes in obese individuals

在巴西圣保罗州坎皮纳斯大学(UNICAMP)进行的研究表明,强力和体重训练等强有力的体育锻炼可以在短时间内减少肥胖和糖尿病患者的累积肝脏脂肪,改善血糖控制,甚至在发生明显的体重减轻之前

在小鼠实验中,UNICAMP运动实验室分子生物学(LaBMEx)的研究人员发现,进行为期两周的运动足以改变肝脏组织中的基因表达,从而“燃烧”更多储存的脂质并有助于非酒精性脂肪肝的治疗。疾病。组织中的细胞胰岛素信号传导得到改善,并且葡萄糖的肝合成减少。

该研究的结果得到了圣保罗研究基金会 – FAPESP的支持,发表在内分泌学杂志上。

“每个人都知道体育锻炼有助于控制疾病。我们的研究主要集中在如何以及为何如此,对所涉及的机制。如果我们能够发现一种关键蛋白质,其水平在训练中上升或下降,我们将朝着发展迈出一步模仿体育锻炼的一些好处的药物,“UNICAMP应用科学学院教授,该研究的主要研究者Leandro Pereira de Moura说。

Moura解释说,肝脏中的多余脂肪会引起局部炎症,这使肝细胞对胰岛素的作用不那么敏感。这种情况可以发展为肝硬化,最终导致肝功能衰竭。

“在患有心脏代谢风险的肥胖个体中,减少肝脏脂肪对于帮助控制糖尿病至关重要,”莫拉说。 “肝脏只能在禁食条件下产生葡萄糖,但如果组织中的胰岛素信号受损,即使摄入碳水化合物,当胰岛素水平升高
老鼠的力量训练

为了研究力量训练对肝脏的影响,进行了涉及三组小鼠的实验。对照组喂养标准饮食(4%脂肪),保持瘦和久坐。第二组和第三组喂食高脂血症(35%脂肪)14周,足够长的时间使动物变得肥胖和患糖尿病。第二组保持久坐不动,而第三组在肥胖和糖尿病后接受中等强度训练运动方案15天。

运动协议包括爬上一个重物附着在尾部的楼梯。每天,老鼠以90秒的间隔爬上楼梯20次。根据Moura的说法,该协议旨在模仿人类的力量训练。

“在我们开始实验之前,我们进行了测试,以确定每只动物可承受的最大负荷。我们在运动过程中使用了相当于此极限值70%的重量。我们小组之前表示,过度训练对非酒精饮料的发展有显着贡献。脂肪肝疾病。过度剧烈运动可能弊大于利,“莫拉说。

研究人员选择了仅仅15天的短时间运动协议,以证明观察到的益处与力量训练直接相关,而不是减肥的次要影响。

事实上,研究人员发现,虽然接受运动训练的小鼠在15天结束时仍然肥胖,但他们的空腹血糖水平正常,而久坐不动的肥胖组的小鼠仍然是糖尿病,直到结束实验。

对肝脏组织的分析显示,与久坐肥胖组的脂肪水平相比,进行运动方案的组中局部脂肪减少25%-30%。运动组中促炎蛋白的数量也减少,但该组小鼠的肝脂肪仍比对照组多约150%。

糖异生

在禁食条件下,肝脏是维持足够血糖水平的主要器官。在糖尿病的情况下,由于胰岛素抗性,不存在糖异生(内源性葡萄糖产生)的控制,并且个体可以变得高血糖。

为了评估力量运动对控制肝脏糖异生的影响,研究人员测试了动物对丙酮酸的耐受性,丙酮酸是肝脏用来产生葡萄糖的主要底物。

“测试基本上包括给小鼠施用丙酮酸并测量肝脏产生的葡萄糖量,”Moura解释说。 “我们发现受过训练的老鼠产生的葡萄糖少于久坐不动的肥胖小鼠,即使它们接受相同数量的底物。这表明受过训练的动物的肝脏经历了代谢改变,使其对胰岛素更敏感。”

接下来,研究人员调查了运动减少肝脏脂肪的机制。为此,研究人员分析了与脂肪生成相关的基因组织表达(脂肪酸和甘油三酯的合成,促进脂肪的积累)和脂肪分解(脂质分解,用作生物体的能量来源)。

“我们通过基因和蛋白质分析将久坐不动的肥胖小鼠与运动小鼠进行了比较,以评估肝脏脂肪的合成和氧化,”Moura说。 “我们观察到久坐小鼠肝脏脂肪积聚的趋势。”

他补充说,该研究的一个重要贡献是证明了力量运动促进了组织的有益改变,这种改变并未直接受到骨骼肌肉收缩的影响。

“我们的下一步将是了解如何处理肌肉和肝脏之间的这种交流。我们的假设是可能涉及一种叫做clusterin的蛋白质,”他说。

如果体育锻炼引起的凝聚素水平升高显示有益,Moura说,可以测试合成替代品的治疗方法。

News Release 

Study shows that strength and weight training can control diabetes in obese individuals

In experiments with mice, Brazilian scientists demonstrated that a moderate training protocol reduced liver fat and made the organ more sensitive to insulin, even before loss of body weight occurred

Fundação de Amparo à Pesquisa do Estado de São Paulo

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IMAGE: A moderate training protocol reduced liver fat and made the organ more sensitive to insulin, even before loss of body weight occurred. view more 

Credit: Guilherme Peruca

Research conducted at the University of Campinas (UNICAMP) in São Paulo State, Brazil, shows that vigorous physical exercise such as strength and weight training can reduce accumulated liver fat and improve blood sugar control in obese and diabetic individuals in a short time span, even before significant weight loss occurs.

In experiments with mice, researchers at UNICAMP’s Molecular Biology of Exercise Laboratory (LaBMEx) found that two weeks of such exercise was sufficient to modify gene expression in liver tissue in ways that “burned” more stored lipids and contributed to the treatment of nonalcoholic fatty liver disease. Cellular insulin signaling in tissue improved, and hepatic synthesis of glucose decreased.

The results of the study, which was supported by São Paulo Research Foundation – FAPESP, are published in the Journal of Endocrinology.

“Everyone knows physical exercise helps control disease. Our research focuses on how and why this is so, on the mechanisms involved. If we can discover a key protein whose levels rise or fall with training, we’ll have taken a step toward the development of drugs that mimic some of the benefits of physical exercise,” said Leandro Pereira de Moura, a professor at UNICAMP’s School of Applied Sciences and the principal investigator of the study.

Moura explained that excess fat in the liver causes local inflammation, which makes liver cells less sensitive to the action of insulin. This condition can progress to cirrhosis and eventually to liver failure.

“In obese individuals at cardiometabolic risk, reducing liver fat is vital to help control diabetes,” Moura told. “The liver should produce glucose only under fasting conditions, but if insulin signaling in tissue is impaired, the liver releases glucose into the blood stream even after ingestion of carbohydrate, when insulin levels are high, and this raises the level of blood sugar.”

Strength training for mice

To investigate the effect of strength training on the liver, an experiment involving three groups of mice was performed. The control group, which was fed a standard diet (4% fat), remained lean and sedentary. The second and third groups were fed a hyperlipidemic diet (35% fat) for 14 weeks, long enough for the animals to become obese and diabetic. The second group remained sedentary, while the third group was submitted to a moderate strength training exercise protocol for 15 days after becoming obese and diabetic.

The exercise protocol consisted of climbing a staircase with a weight attached to the tail. Each day, the mice climbed the stairs 20 times at 90-second intervals. According to Moura, the protocol was designed to mimic strength training in humans.

“Before we began the experiment, we conducted tests to determine the maximum load each animal could bear. We used a weight corresponding to 70% of this limit in the exercise sessions. Our group had previously shown overtraining can contribute significantly to the development of nonalcoholic fatty liver disease. Excessively strenuous exercise can do more harm than good,” Moura said.

The researchers opted for a short exercise protocol of only 15 days to demonstrate that the benefits observed were directly linked to strength training and not to the secondary effects of weight loss.

In fact, the researchers found that although the mice submitted to exercise training were still obese at the end of the 15-day period, their fasting blood sugar levels were normal, whereas the mice in the sedentary obese group remained diabetic until the end of the experiment.

An analysis of liver tissue showed a 25%-30% reduction in local fat in the group that performed the exercise protocol compared with the fat level of the sedentary obese group. The quantity of proinflammatory proteins was also reduced in the exercise group, and yet the mice in that group still had approximately 150% more liver fat than the control group.

Gluconeogenesis

In fasting conditions, the liver is the main organ responsible for maintaining adequate blood sugar levels. In the context of diabetes, control of gluconeogenesis (endogenous glucose production) is absent as a result of insulin resistance, and the individual can become hyperglycemic.

To evaluate the effect of strength exercise on the control of hepatic gluconeogenesis, the researchers tested the animals for tolerance of pyruvate, the main substrate used by the liver to produce glucose.

“The test consisted basically of administering pyruvate to the mice and measuring the amount of glucose produced by the liver,” Moura explained. “We found that the trained mice produced less glucose than the sedentary obese mice even though they received the same amount of substrate. This showed that the trained animal’s liver underwent metabolic alterations that made it more sensitive to insulin.”

Next, the researchers investigated the mechanism by which exercise reduced liver fat. To do this, the researchers analyzed the tissue expression of genes associated with lipogenesis (synthesis of fatty acids and triglycerides, contributing to the accumulation of fat) and lipolysis (breakdown of lipids for use as an energy source by the organism).

“We compared the sedentary obese mice with the exercised mice by means of gene and protein analyses to evaluate the synthesis and oxidation of liver fat,” Moura said. “We observed a tendency towards more liver fat accumulation in the sedentary mice.”

He added that an important contribution of the study was its demonstration that strength exercise promoted beneficial alterations in tissue that was not directly acted upon by skeletomuscular contractions.

“Our next step will be to find out how this communication between muscles and liver is processed. Our hypothesis is that a protein called clusterin may be involved,” he said.

If the rise in clusterin levels induced by physical exercise is shown to be beneficial, Moura said, treatments with synthetic alternatives could be tested.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

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