Hakkak Reza, Rose Shannon, Spray Beverly, Kozaczek Melisa, Korourian Soheila
Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Biomed Rep. 2021 Jun;14(6):49. doi: 10.3892/br.2021.1425. Epub 2021 Mar 30.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in adolescents and adults, and the risk of developing NAFLD increases with obesity. In the present study, it was shown that obesity increased fatty liver (steatosis) using an obese Zucker rat model. Metformin is an oral anti-hyperglycemic agent approved by the FDA for treatment of type 2 diabetes in adults and children >10 years of age. There is insufficient evidence regarding the effects of metformin on pediatric liver steatosis. Thus, in the present study, the effects of 10 weeks metformin treatment on liver steatosis and related serum markers for liver damage was assessed. Lean and obese (n=16 per group) 5-week old female Zucker rats were provided an AIN-93 G diet for 8 weeks to induce NAFLD, and then rats were randomly assigned to 4 groups (8 rats/group): i) lean without metformin (LC), ii) lean + metformin (LM), iii) obese without metformin (OC), and iv) obese + metformin (OM). Rats were provided access to the diet containing metformin (1 g metformin per kg of food). Rats were weighed twice weekly and were sacrificed 10 weeks later. Serum was collected to measure the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), leptin and adiponectin. Livers were collected for histological analysis. The results showed that obese rats gained significantly more weight than lean rats in both the control and metformin treatment groups (P<0.001). OM treated rats exhibited a lower degree of liver steatosis compared with the OC rats (P<0.04). There were no significant differences in serum ALT levels between the groups. However, obesity significantly increased serum AST levels in both the control and metformin treatment groups (P=0.01). The ratio of leptin to adiponectin was increased in obese compared with the lean rats in both the control and metformin treatment groups (P<0.0001). There was no effect of metformin on serum biomarkers. In summary, short-term metformin treatment decreased liver steatosis but did not affect the serum markers of liver steatosis.
非酒精性脂肪性肝病（NAFLD）是青少年和成年人肝病的主要病因，且患NAFLD的风险会随着肥胖而增加。在本研究中，利用肥胖Zucker大鼠模型表明肥胖会增加脂肪肝（脂肪变性）。二甲双胍是一种经美国食品药品监督管理局（FDA）批准用于治疗10岁及以上成人和儿童2型糖尿病的口服降糖药。关于二甲双胍对儿童肝脏脂肪变性影响的证据不足。因此，在本研究中，评估了为期10周的二甲双胍治疗对肝脏脂肪变性及肝脏损伤相关血清标志物的影响。给5周龄的瘦型和肥胖型（每组n = 16）雌性Zucker大鼠提供AIN - 93 G饮食8周以诱导NAFLD，然后将大鼠随机分为4组（每组8只大鼠）：i）未用二甲双胍的瘦型大鼠（LC），ii）瘦型 + 二甲双胍（LM），iii）未用二甲双胍的肥胖型大鼠（OC），iv）肥胖型 + 二甲双胍（OM）。给大鼠提供含二甲双胍的饮食（每千克食物含1 g二甲双胍）。每周称重大鼠两次，10周后处死大鼠。收集血清以测量天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、瘦素和脂联素的水平。收集肝脏进行组织学分析。结果表明，在对照组和二甲双胍治疗组中，肥胖大鼠体重增加均显著多于瘦型大鼠（P < 0.001）。与OC大鼠相比，OM治疗的大鼠肝脏脂肪变性程度较低（P < 0.04）。各组之间血清ALT水平无显著差异。然而，在对照组和二甲双胍治疗组中，肥胖均显著增加血清AST水平（P = 0.01）。在对照组和二甲双胍治疗组中，与瘦型大鼠相比，肥胖大鼠的瘦素与脂联素比值均升高（P < 0.0001）。二甲双胍对血清生物标志物无影响。总之，短期二甲双胍治疗可减轻肝脏脂肪变性，但不影响肝脏脂肪变性的血清标志物。
