Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model.
Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model.
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DOI：
10.3390/ijms222312844
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发表时间：
2021-11-27
影响因子：
5.6
通讯作者：
Tsuneyama K
中科院分区：
文献类型：
--
作者：
Ichimura-Shimizu M;Kageyama T;Oya T;Ogawa H;Matsumoto M;Sumida S;Kakimoto T;Miyakami Y;Nagatomo R;Inoue K;Cheng C;Tsuneyama K
代谢综合征（MS）是2型糖尿病、血管炎症、动脉粥样硬化以及肾脏、肝脏和心脏疾病的危险因素。非酒精性脂肪性肝炎（NASH）是一种进行性的代表性肝病，可导致肝硬化和肝细胞癌等不可逆的灾难。代谢紊乱如高血糖症已被广泛报道与NASH中的肝癌发生有关;然而，仍缺乏高血糖症与肝癌发生之间联系的直接证据。Tsumura Suzuki肥胖糖尿病（TSOD）小鼠自发地发展代谢综合征，包括肥胖、胰岛素抵抗和NASH样肝脏表型，并最终发展肝细胞癌。TSOD小鼠提供了自发的人类MS样模型，即使存在显着的个体差异。在这项研究中，我们监测了小鼠的血糖水平，体重，胰腺和肝脏病变随时间的变化。因此，与高血糖小鼠相比，非高血糖TSOD小鼠的肝癌发生延迟。此外，在40周的终止点，24只高血糖TSOD小鼠中有18只（75%）出现肝肿瘤;相比之下，24只非高血糖小鼠中只有5只（20.8%）出现肝肿瘤。接下来，我们研究了三种寡糖，可以降低高血糖TSOD小鼠的血糖水平。我们监测血糖和尿糖水平，并评估实验组之间的胰腺病变。正如预期的那样，在喂食乳源性低聚糖（低聚半乳糖和低聚乳蔗糖）的TSOD小鼠中发现血糖和尿糖水平显著降低，朗格汉斯细胞缺失较小。在24周龄时，在肝脏中发现轻度脂肪性肝炎，但没有证据表明肝脏致癌。在乳源性低聚糖给药组中，肝脏脂肪变性得到缓解。总之，从年轻时开始抑制血糖水平的增加可以防止易感个体患糖尿病和NAFLD/NASH的发病，以及致癌作用。牛奶来源的低聚糖显示出降低血糖水平的作用，这可能是预期防止肝癌发生。
Metabolic syndrome (MS) is a risk factor for type 2 diabetes mellitus, vascular inflammation, atherosclerosis, and renal, liver, and heart diseases. Non-alcoholic steatohepatitis (NASH) is a progressive representative liver disease and may lead to the irreversible calamities of cirrhosis and hepatocellular carcinoma. Metabolic disorders such as hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between hyperglycemia and carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop metabolic syndrome, including obesity, insulin resistance, and NASH-like liver phenotype, and eventually develop hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in blood glucose levels, body weights, and pancreatic and liver lesions over time. As a result, liver carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of oligosaccharide that could lower blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived oligosaccharides (galactooligosaccharides and lactosucrose). At the age of 24 weeks, mild steatohepatitis was found in the liver but there was no evidence of liver carcinogenesis. Steatosis in the liver was alleviated in the milk-derived oligosaccharide-administered group. Taken together, suppressing the increase in blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of NAFLD/NASH, as well as carcinogenesis. Milk-derived oligosaccharides showed a lowering effect on blood glucose levels, which may be expected to prevent liver carcinogenesis.
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影响因子：
4.6
作者：
Liu F;Li P;Chen M;Luo Y;Prabhakar M;Zheng H;He Y;Qi Q;Long H;Zhang Y;Sheng H;Zhou H
通讯作者：
Zhou H
DOI：
10.3390/molecules26020331
发表时间：
2021-01-11
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lee JY;Kim TY;Kang H;Oh J;Park JW;Kim SC;Kim M;Apostolidis E;Kim YC;Kwon YI
通讯作者：
Kwon YI
影响因子：
3.9
作者：
Pais R;Maurel T
通讯作者：
Maurel T
影响因子：
3.7
作者：
Micucci, Carla;Orciari, Silvia;Catalano, Alfonso
通讯作者：
Catalano, Alfonso
影响因子：
5.6
作者：
Weitkunat, Karolin;Schumann, Sara;Klaus, Susanne
通讯作者：
Klaus, Susanne