Diabetes Breakthrough: Fish Oil May Reverse Insulin Resistance 糖尿病突破：鱼油可逆转胰岛素抵抗
Fish oil supplementation modified the profile of defense cells, shifting them from a pro-inflammatory to an anti-inflammatory state, effectively reversing a condition resembling type 2 diabetes.
鱼油补充剂可改变防御细胞的特性，使其从促炎状态转变为抗炎状态，从而有效逆转类似2型糖尿病的症状。
A Brazilian study published in Nutrients suggests that fish oil may help reduce insulin resistance and improve glucose tolerance by influencing the body’s inflammatory response.
巴西一项发表在《营养》杂志上的研究表明，鱼油可通过影响人体的炎症反应，帮助降低胰岛素抵抗并改善葡萄糖耐受性。
Funded by FAPESP, the study was conducted on rats that, while not obese, exhibited a condition resembling type 2 diabetes—a disorder marked by high blood sugar levels due to diminished insulin effectiveness.
这项研究由FAPESP资助，对非肥胖但患有类似2型糖尿病症状的小鼠鼠进行了实验。2型糖尿病是一种因胰岛素效力下降而导致血糖水平升高的疾病。
As the authors explain, supplementation with omega-3 fatty acids such as those present in fish oil has been prescribed for individuals with cardiovascular problems and type 2 diabetes, but the effects of these nutrients on insulin resistance without obesity are poorly understood.
正如作者所解释的那样，补充欧米伽-3脂肪酸（如鱼油中的脂肪酸）已被用于治疗心血管疾病和2型糖尿病患者，但人们对这些营养素对非肥胖胰岛素抵抗的影响知之甚少。
In this study, the researchers observed that administration of 2 grams of fish oil per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times per week for eight weeks reduced insulin resistance in non-obese rats, which also displayed improved levels of blood sugar, inflammatory markers and lipid features, including total cholesterol, LDL (“bad cholesterol”) and triglycerides.
在这项研究中，研究人员观察到，每公斤体重服用2克鱼油（相当于540毫克/克二十碳五烯酸或EPA和100毫克/克二十二碳六烯酸或DHA） 每周三次，持续八周，非肥胖大鼠的胰岛素抵抗性降低，血糖、炎症指标和血脂水平（包括总胆固醇、低密度脂蛋白（“坏胆固醇”）和甘油三酯）也得到改善。
Potential Implications for Diabetes Treatment
对糖尿病治疗的潜在意义
Although the findings resulted from preclinical trials, they offer hope for non-obese type 2 diabetes patients, or 10%-20% of the worldwide total with the disease.
虽然这些发现来自临床前试验，但它们为非肥胖2型糖尿病患者带来了希望，这类患者占全球糖尿病总人数的10%至20%。
“Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes. We found that insulin resistance can be reduced in these animals by modulating the inflammatory response so as to change the profile of defense cells [lymphocytes] from a pro-inflammatory state to an anti-inflammatory state. This process parallels the response of obese individuals with insulin resistance to omega-3 fatty acid supplementation,” said Rui Curi, Director of Butantan Institute’s Education Center, Professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL), and coordinator of the study.
“我们的实验使用了Goto-Kakizaki [GK]大鼠，这是一种非肥胖型2型糖尿病的动物模型。我们发现，通过调节炎症反应，使防御细胞（淋巴细胞）从促炎状态转变为抗炎状态，可以降低这些动物的胰岛素抵抗。这个过程与肥胖者对补充欧米伽-3脂肪酸的反应相似，”布坦坦研究所教育中心主任、南克鲁塞罗大学（UNICSUL）健康科学跨学科研究生课程教授兼该研究协调员Rui Curi说道。
Alterations in lymphocytes, white blood cells that orchestrate the adaptive immune response, tend to have an impact on other immune system cells, triggering a cascade effect. “In previous studies, we observed alterations in both lymphocytes and macrophages [large white blood cells that often reside in adipose tissue and are part of the innate immune system, engulfing and destroying pathogens] in non-obese rats with insulin resistance. In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes,” Curi explained.
负责协调适应性免疫反应的白血球——淋巴细胞的变化往往会对免疫系统的其他细胞产生影响，引发连锁反应。Curi解释道：“在之前的实验中，我们发现胰岛素抵抗的非肥胖大鼠的淋巴细胞和巨噬细胞（常驻于脂肪组织中的大型白血球，属于先天免疫系统的一部分，吞噬并消灭病原体）均发生了变化。在这种情况下，这些细胞会产生更多的促炎细胞因子，而这正是肥胖糖尿病患者的核心问题，”Curi解释道。
“The main aim of the study, therefore, was to find out whether supplementation with fish oil [rich in omega-3] could reverse specific alterations in lymphocytes that had been observed in previous research. Our findings increased our knowledge of the link between inflammation and insulin resistance in non-obese animals, confirming that this is a key factor in diabetes even in the absence of obesity,” said Renata Gorjão, last author of the article, and Co-Director of UNICSUL’s Program of Graduate Studies in Health Sciences.
“因此，这项研究的主要目的是了解补充鱼油（富含欧米伽-3）是否可以逆转先前研究中观察到的淋巴细胞特定变化。我们的发现加深了我们对非肥胖动物炎症与胰岛素抵抗之间关系的认识，证实了即使在非肥胖状态下，这也是糖尿病的关键因素，”文章最后作者、UNICSUL健康科学研究生项目联合主任Renata Gorjão说道。
Systemic inflammation
全身炎症
The investigation described in the Nutrients article, conducted during the PhD candidacy of Tiago Bertola Lobato, was part of a larger project supported by FAPESP that is deepening scientists’ understanding of insulin resistance in non-obese animals.
《营养》杂志文章中描述的调查由蒂亚戈·贝尔托拉·洛巴托（Tiago Bertola Lobato）在攻读博士学位期间进行，是FAPESP支持的一个大型项目的一部分，该项目旨在加深科学家对非肥胖动物胰岛素抵抗的理解。
According to Curi, obesity is a major risk factor for diabetes, albeit not the only one. In the case of non-obese diabetes patients, the primary hypothesis is that the cause is genetic. In an article published in the journal Cells, Curi, Gorjão et al. describe an investigation into the possibility that insulin resistance in the non-obese may also be linked to delayed intestinal transit.
Curi认为，肥胖是糖尿病的主要风险因素，但不是唯一因素。对于非肥胖糖尿病患者，主要假设是遗传因素。在《细胞》杂志上发表的一篇文章中，Curi、Gorjão等人描述了一项调查，即非肥胖患者的胰岛素抵抗也可能与肠道蠕动延迟有关。
“Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways. Adipose tissue, which is augmented in obesity, releases pro-inflammatory cytokines that affect the insulin signaling pathways, promoting insulin resistance. In the non-obese model, this impactful characteristic of adipose tissue is absent, but systemic inflammation is present,” Curi said.
“大多数肥胖者都有慢性低度炎症，众所周知，这种炎症会影响胰岛素信号传导通路。肥胖时增生的脂肪组织会释放促炎细胞因子，影响胰岛素信号传导通路，从而促进胰岛素抵抗。在非肥胖模型中，脂肪组织没有这种影响性的特征，但存在全身炎症，”Curi说道。
Systemic inflammation in non-obese GK rats with insulin resistance was demonstrated by the group in a previous study published in the International Journal of Molecular Sciences.
该研究小组在《国际分子科学杂志》上发表的前一篇研究中证实了非肥胖GK大鼠胰岛素抵抗的全身炎症。
In another article relating to the same project, the researchers reported an early breakdown of anti-inflammatory mechanisms in non-obese GK rats with insulin resistance. Lymph nodes (part of the immune system) in newly weaned 21-day-old GK pups already exhibited a reduction in markers of regulatory T-cells (Tregs, cells with anti-inflammatory characteristics). Other early inflammatory alterations were also observed in the rats. The article is published in FEBS Letters, a journal of the Federation of European Biochemical Societies.
在有关同一项目的另一篇文章中，研究人员报告了胰岛素抵抗的非肥胖GK大鼠的抗炎机制的早期崩溃。刚断奶的21天大的GK幼崽的淋巴结（免疫系统的一部分）已经表现出调节性T细胞（Treg，具有抗炎特性的细胞）标记物的减少。在实验鼠身上还观察到了其他早期炎症变化。该论文发表在欧洲生物化学学会联合会期刊《FEBS Letters》上。
“Fish oil supplementation reversed this pro-inflammatory profile, displaying a significant anti-inflammatory effect and reducing polarization of Th1 and Th17 cells [lymphocyte subtypes that perform crucial functions in inflammation], followed by a rise in the percentage of Tregs, which can inhibit the activation of pro-inflammatory lymphocytes. Thus the action of omega-3 fatty acids on lymphocytes, modulating them from a pro-inflammatory state to an anti-inflammatory state, may have triggered the reduction in insulin resistance in these animals,” Lobato said.
“补充鱼油可以逆转这种促炎性特征，显示出显著的抗炎作用，并减少Th1和Th17细胞（在炎症中发挥关键功能的淋巴细胞亚型）的极化，随后调节性T细胞（Tregs）的百分比上升，可以抑制促炎性淋巴细胞的激活。因此，ω-3脂肪酸对淋巴细胞的作用，即从促炎状态调节到抗炎状态，可能引发了这些动物胰岛素抵抗的降低，”洛巴托说道。
Despite the good news, the researchers stressed that more research is needed to confirm their findings. “These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid,” Curi said.
尽管有好消息，研究人员强调，还需要更多的研究来证实他们的发现。Curi说：“这些研究涉及成熟的实验模型，模拟非肥胖人群的胰岛素抵抗。还需要进行人体试验，以评估理想的剂量和最合适的omega-3脂肪酸类型。”
Fish oil supplementation modified the profile of defense cells, shifting them from a pro-inflammatory to an anti-inflammatory state, effectively reversing a condition resembling type 2 diabetes.
鱼油补充剂可改变防御细胞的特性，使其从促炎状态转变为抗炎状态，从而有效逆转类似2型糖尿病的症状。
A Brazilian study published in Nutrients suggests that fish oil may help reduce insulin resistance and improve glucose tolerance by influencing the body’s inflammatory response.
巴西一项发表在《营养》杂志上的研究表明，鱼油可通过影响人体的炎症反应，帮助降低胰岛素抵抗并改善葡萄糖耐受性。
Funded by FAPESP, the study was conducted on rats that, while not obese, exhibited a condition resembling type 2 diabetes—a disorder marked by high blood sugar levels due to diminished insulin effectiveness.
这项研究由FAPESP资助，对非肥胖但患有类似2型糖尿病症状的小鼠鼠进行了实验。2型糖尿病是一种因胰岛素效力下降而导致血糖水平升高的疾病。
As the authors explain, supplementation with omega-3 fatty acids such as those present in fish oil has been prescribed for individuals with cardiovascular problems and type 2 diabetes, but the effects of these nutrients on insulin resistance without obesity are poorly understood.
正如作者所解释的那样，补充欧米伽-3脂肪酸（如鱼油中的脂肪酸）已被用于治疗心血管疾病和2型糖尿病患者，但人们对这些营养素对非肥胖胰岛素抵抗的影响知之甚少。
In this study, the researchers observed that administration of 2 grams of fish oil per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times per week for eight weeks reduced insulin resistance in non-obese rats, which also displayed improved levels of blood sugar, inflammatory markers and lipid features, including total cholesterol, LDL (“bad cholesterol”) and triglycerides.
在这项研究中，研究人员观察到，每公斤体重服用2克鱼油（相当于540毫克/克二十碳五烯酸或EPA和100毫克/克二十二碳六烯酸或DHA） 每周三次，持续八周，非肥胖大鼠的胰岛素抵抗性降低，血糖、炎症指标和血脂水平（包括总胆固醇、低密度脂蛋白（“坏胆固醇”）和甘油三酯）也得到改善。
Potential Implications for Diabetes Treatment
对糖尿病治疗的潜在意义
Although the findings resulted from preclinical trials, they offer hope for non-obese type 2 diabetes patients, or 10%-20% of the worldwide total with the disease.
虽然这些发现来自临床前试验，但它们为非肥胖2型糖尿病患者带来了希望，这类患者占全球糖尿病总人数的10%至20%。
“Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes. We found that insulin resistance can be reduced in these animals by modulating the inflammatory response so as to change the profile of defense cells [lymphocytes] from a pro-inflammatory state to an anti-inflammatory state. This process parallels the response of obese individuals with insulin resistance to omega-3 fatty acid supplementation,” said Rui Curi, Director of Butantan Institute’s Education Center, Professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL), and coordinator of the study.
“我们的实验使用了Goto-Kakizaki [GK]大鼠，这是一种非肥胖型2型糖尿病的动物模型。我们发现，通过调节炎症反应，使防御细胞（淋巴细胞）从促炎状态转变为抗炎状态，可以降低这些动物的胰岛素抵抗。这个过程与肥胖者对补充欧米伽-3脂肪酸的反应相似，”布坦坦研究所教育中心主任、南克鲁塞罗大学（UNICSUL）健康科学跨学科研究生课程教授兼该研究协调员Rui Curi说道。
Alterations in lymphocytes, white blood cells that orchestrate the adaptive immune response, tend to have an impact on other immune system cells, triggering a cascade effect. “In previous studies, we observed alterations in both lymphocytes and macrophages [large white blood cells that often reside in adipose tissue and are part of the innate immune system, engulfing and destroying pathogens] in non-obese rats with insulin resistance. In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes,” Curi explained.
负责协调适应性免疫反应的白血球——淋巴细胞的变化往往会对免疫系统的其他细胞产生影响，引发连锁反应。Curi解释道：“在之前的实验中，我们发现胰岛素抵抗的非肥胖大鼠的淋巴细胞和巨噬细胞（常驻于脂肪组织中的大型白血球，属于先天免疫系统的一部分，吞噬并消灭病原体）均发生了变化。在这种情况下，这些细胞会产生更多的促炎细胞因子，而这正是肥胖糖尿病患者的核心问题，”Curi解释道。
“The main aim of the study, therefore, was to find out whether supplementation with fish oil [rich in omega-3] could reverse specific alterations in lymphocytes that had been observed in previous research. Our findings increased our knowledge of the link between inflammation and insulin resistance in non-obese animals, confirming that this is a key factor in diabetes even in the absence of obesity,” said Renata Gorjão, last author of the article, and Co-Director of UNICSUL’s Program of Graduate Studies in Health Sciences.
“因此，这项研究的主要目的是了解补充鱼油（富含欧米伽-3）是否可以逆转先前研究中观察到的淋巴细胞特定变化。我们的发现加深了我们对非肥胖动物炎症与胰岛素抵抗之间关系的认识，证实了即使在非肥胖状态下，这也是糖尿病的关键因素，”文章最后作者、UNICSUL健康科学研究生项目联合主任Renata Gorjão说道。
Systemic inflammation
全身炎症
The investigation described in the Nutrients article, conducted during the PhD candidacy of Tiago Bertola Lobato, was part of a larger project supported by FAPESP that is deepening scientists’ understanding of insulin resistance in non-obese animals.
《营养》杂志文章中描述的调查由蒂亚戈·贝尔托拉·洛巴托（Tiago Bertola Lobato）在攻读博士学位期间进行，是FAPESP支持的一个大型项目的一部分，该项目旨在加深科学家对非肥胖动物胰岛素抵抗的理解。
According to Curi, obesity is a major risk factor for diabetes, albeit not the only one. In the case of non-obese diabetes patients, the primary hypothesis is that the cause is genetic. In an article published in the journal Cells, Curi, Gorjão et al. describe an investigation into the possibility that insulin resistance in the non-obese may also be linked to delayed intestinal transit.
Curi认为，肥胖是糖尿病的主要风险因素，但不是唯一因素。对于非肥胖糖尿病患者，主要假设是遗传因素。在《细胞》杂志上发表的一篇文章中，Curi、Gorjão等人描述了一项调查，即非肥胖患者的胰岛素抵抗也可能与肠道蠕动延迟有关。
“Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways. Adipose tissue, which is augmented in obesity, releases pro-inflammatory cytokines that affect the insulin signaling pathways, promoting insulin resistance. In the non-obese model, this impactful characteristic of adipose tissue is absent, but systemic inflammation is present,” Curi said.
“大多数肥胖者都有慢性低度炎症，众所周知，这种炎症会影响胰岛素信号传导通路。肥胖时增生的脂肪组织会释放促炎细胞因子，影响胰岛素信号传导通路，从而促进胰岛素抵抗。在非肥胖模型中，脂肪组织没有这种影响性的特征，但存在全身炎症，”Curi说道。
Systemic inflammation in non-obese GK rats with insulin resistance was demonstrated by the group in a previous study published in the International Journal of Molecular Sciences.
该研究小组在《国际分子科学杂志》上发表的前一篇研究中证实了非肥胖GK大鼠胰岛素抵抗的全身炎症。
In another article relating to the same project, the researchers reported an early breakdown of anti-inflammatory mechanisms in non-obese GK rats with insulin resistance. Lymph nodes (part of the immune system) in newly weaned 21-day-old GK pups already exhibited a reduction in markers of regulatory T-cells (Tregs, cells with anti-inflammatory characteristics). Other early inflammatory alterations were also observed in the rats. The article is published in FEBS Letters, a journal of the Federation of European Biochemical Societies.
在有关同一项目的另一篇文章中，研究人员报告了胰岛素抵抗的非肥胖GK大鼠的抗炎机制的早期崩溃。刚断奶的21天大的GK幼崽的淋巴结（免疫系统的一部分）已经表现出调节性T细胞（Treg，具有抗炎特性的细胞）标记物的减少。在实验鼠身上还观察到了其他早期炎症变化。该论文发表在欧洲生物化学学会联合会期刊《FEBS Letters》上。
“Fish oil supplementation reversed this pro-inflammatory profile, displaying a significant anti-inflammatory effect and reducing polarization of Th1 and Th17 cells [lymphocyte subtypes that perform crucial functions in inflammation], followed by a rise in the percentage of Tregs, which can inhibit the activation of pro-inflammatory lymphocytes. Thus the action of omega-3 fatty acids on lymphocytes, modulating them from a pro-inflammatory state to an anti-inflammatory state, may have triggered the reduction in insulin resistance in these animals,” Lobato said.
“补充鱼油可以逆转这种促炎性特征，显示出显著的抗炎作用，并减少Th1和Th17细胞（在炎症中发挥关键功能的淋巴细胞亚型）的极化，随后调节性T细胞（Tregs）的百分比上升，可以抑制促炎性淋巴细胞的激活。因此，ω-3脂肪酸对淋巴细胞的作用，即从促炎状态调节到抗炎状态，可能引发了这些动物胰岛素抵抗的降低，”洛巴托说道。
Despite the good news, the researchers stressed that more research is needed to confirm their findings. “These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid,” Curi said.
尽管有好消息，研究人员强调，还需要更多的研究来证实他们的发现。Curi说：“这些研究涉及成熟的实验模型，模拟非肥胖人群的胰岛素抵抗。还需要进行人体试验，以评估理想的剂量和最合适的omega-3脂肪酸类型。”