Abstract
Aim The purpose of this study was to explore the effect of a novel identified peptide hormone “metabolitin” on lipid absorption in the small intestine of mice with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) and potential mechanisms. Methods T2DM was induced in mice by 4–6 weeks of high-fat diets followed by intraperitoneal injection of 35 mg/kg STZ. NAFLD was induced in diabetic mice by a month of high-fat diets. Oral administration of 4 pmol/g or 12 pmol/g metabolitin every two days was performed during one-month high-fat diets. Triglyceride (TG) and total cholesterol (TC) detection and Oil Red O staining were performed to evaluate lipid absorption. The neurotensin (NT) levels in the intestinal tissues and serum were determined by ELISA. Lipogenesis- and lipolysis-related proteins, AMP-activated protein kinase (AMPK), and p-AMPK were examined by Western blot analysis. Results It was found that glucose tolerance test (GTT), insulin tolerance test (ITT), TG, and TC indicated lower levels in the serum of NAFLD/T2DM mice receiving 4 pmol/g and 12 pmol/g metabolitin compared to the mice receiving normal saline (P < 0.05). No significant difference was noted in the TC level of the feces among mice with different diets (P > 0.05), but compared to NAFLD/T2DM mice with normal saline, the mice administrated with 4 pmol/g and 12 pmol/g metabolitin revealed much higher TG levels in the feces (P < 0.05). The results of Oil Red O staining revealed that the intestinal epithelial cells of NAFLD/T2DM mice receiving 12 pmol/g metabolitin indicated resistance to lipid absorption and the area of staining was smaller than that of NAFLD/T2DM mice with normal saline (P < 0.05). The NAFLD/T2DM mice receiving 4 pmol/g and 12 pmol/g metabolitin showed a higher extent of p-AMPK concomitant with lower levels of NT in the serum and small intestine than the mice with normal saline (P < 0.05). Western blot analysis also suggested that NAFLD/T2DM mice receiving 4 pmol/g and 12 pmol/g metabolitin revealed lower expressions in fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase-1 (SCD-1), and sterol regulatory element-binding transcription factor-1 (SREBP1) proteins and higher expressions in carnitine palmitoyltransferase 1 (CPT1), peroxisome proliferator-activated receptor alpha (PPARα), and fatty acid translocase (CD36) proteins than NAFLD/T2DM mice with normal saline (P < 0.05). Conclusion According to the data we observed, oral administration of metabolitin could attenuate lipid absorption in the small intestine of NAFLD/T2DM mice, which may be a novel therapeutic approach for NAFLD/T2DM.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a syndrome characterized by excessive fat accumulation in liver cells, which is not caused by alcohol and other definite liver damaging factors
During 8 to 12 weeks, glucose tolerance test (GTT) was performed on the mice with a high-fat diet. e evaluation of successful prediabetic model was performed according to the following criteria: (a) impaired glucose tolerance (IGT) was with a slight change in fasting blood glucose (FBG); (b) blood glucose increased significantly at 15–120 min after glucose loading; (c) features of insulin resistance were revealed after the insulin tolerance test (ITT). e area under curve (AUC) during an oral GTT and ITT was used to evaluate the patterns of glucose and insulin resistance changes
Oral Administration of Metabolitin Attenuated Abnormal Glycolipid Metabolism in type 2 diabetes mellitus (T2DM)/NAFLD Mice. e serum levels of total cholesterol (TC) and TG as well as the area under curve (AUC) of GTT and ITT were examined in all mice in order to confirm whether the oral administration of metabolitin can regulate glycolipid metabolism in T2DM/NAFLD mice
Summary
Nonalcoholic fatty liver disease (NAFLD) is a syndrome characterized by excessive fat accumulation in liver cells (hepatic steatosis ≥5%), which is not caused by alcohol and other definite liver damaging factors. NAFLD patients are more likely to suffer from metabolic syndrome, such as obesity, insulin resistance, type 2 diabetes mellitus (T2DM), dyslipidemia, and hypertension [5, 6]. Among these complications, T2DM seems to be the essential clinical predictor of adverse clinical reactions, such as advanced liver fibrosis and mortality in NAFLD patients [7, 8]. Accumulated evidence has confirmed the correlation between NAFLD and T2DM, which could elaborate lipid metabolism defects and hepatic triacylglycerol (TG) accumulation processed to insulin resistance (IR) and hyperinsulinemia in NAFLD patients or to pancreatic β-cell dysfunction in T2DM patients [12, 13]
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