Pathological Changes in Hepatocytes of Mice with Obesity-induced Type 2 Diabetes by Monosodium Glutamate

Abstract

Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice signiˆcantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, we observed eosin-negative accumulations of hepatocytes around central veins in the hepatic lobule. By Oil-Red O staining, the eosin-negative granules were identiˆed in the lipid droplets. We then ascertained whether these lipid droplets of hepatocytes in the obese mice could be modiˆed by diet. After 24 h of diet restriction, the lipid droplets of hepatocytes in the obese mice were swollen. Furthermore, after 48 h of the diet restriction, the lipid droplets continued swelling and the autophagy-like structures that were found in the healthy mice under the same condition in the obese mice were not observed. These results suggest that the obese mice might have delayed energy metabolism, which might have in‰uenced the mechanisms of hepatocytes. Theseˆndings provide new insight into the functional changes in chronic obesity-induced type 2 diabetes and it is possible that the pathological feature make a contribution to promise the target of pharmacological therapy.Key words-centrolobular fatty degeneration; hepatocyte; obesity-induced type 2 diabetes; pathological change; scanning electron microscopy; transmission electron microscopy 緒 言

Dilatation of Sinusoidal Capillary and Swelling of Sinusoidal Fenestration in Obesity: An Ultrastructural Study

“…The fenestrations of the sinusoidal wall are not immobilized, and the progression of liver fibrosis because of hepatitis leads to the development of basal membranes of the sinusoidal endothelium and a decrease in the number of fenestrations [18,19]. Our previous ultrastructural analysis using scanning electron microscopy also indicated that the sinusoids may be altered in fatty liver [10]. Therefore, it is important to clarify the pathological changes of sinusoids in chronic obesity because it is possible that the functional changes in sinusoids, such as transportation to hepatocytes through the fenestrations of the sinusoidal wall, are analogized.…”

“…An obesity-induction method using monosodium glutamate (MSG) was used in accordance with our previous report [10]. Fourteen male C57BL/6J mice were intrasubcutaneously injected with MSG (2 mg/g of body weight, Wako Pure Chemical Industries, Ltd., Osaka, Japan) on postnatal days 1, 2, 4, 6, 8, and 10.…”

“…In histological analysis, we reported that many lipid droplets were accumulated in hepatocytes in fatty liver using data of blood biochemical values such as nonesterified fatty acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride [10]. In chronic obesity or NAFLD, other experiments also showed that lipid droplets accumulate in hepatocytes [2,11].…”

Progressive Depletion of Rough Endoplasmic Reticulum in Epithelial Cells of the Small Intestine in Monosodium Glutamate Mice Model of Obesity

“…As reported in our previous studies, MSG was used to induce obesity [ 19 , 21 ]. On postnatal days 1, 2, 4, 6, 8, and 10, eight male C57BL/6J mice were intrasubcutaneously injected with MSG (2 mg/g of body weight; Wako Pure Chemical Industries, Ltd., Japan).…”

“…In a previous study of mice with monosodium glutamate- (MSG-) induced obesity, we found that lipid droplets accumulated in the hepatocytes of obese mice and levels of nonesterified fatty acid (NEFA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were increased compared to controls [ 19 ]. Other studies have also reported that lipid droplets accumulate in hepatocytes in chronic obesity and NAFLD [ 1 , 20 ].…”