Temporal Relationship between Diet-Induced Steatosis and Onset of Insulin/Leptin Resistance in Male Wistar Rats
| Autor: | Yingli Ge, Guang Ji, Li Zhang, Haiyan Song, Zemin Yao |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Leptin Male medicine.medical_specialty Lipoproteins medicine.medical_treatment Hypothalamus lcsh:Medicine Diet High-Fat Insulin resistance Dietary Sucrose Hyperinsulinism Internal medicine medicine Hyperinsulinemia Animals Insulin Rats Wistar lcsh:Science Dyslipidemias Inflammation Multidisciplinary biology lcsh:R digestive oral and skin physiology Lipid Metabolism medicine.disease Lipids IRS1 Fatty Liver Insulin receptor Endocrinology Liver Hyperglycemia biology.protein lcsh:Q Insulin Resistance Metabolic syndrome hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 2, p e0117008 (2015) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0117008 |
| Popis: | Rats fed with high-fat-high-sucrose (HFHS) diet are known to manifest metabolic syndrome including hyperinsulinemia, hyperleptinemia, hyperglycemia, diabetic dyslipidemia, and hepatic steatosis. The aim of the current study is to determine the temporal relationships between the development of hepatic steatosis and the onset of insulin and leptin resistance in hypothalamus and liver in male Wistar rats (six weeks of age) fed chow or HFHS diet for up to 8 weeks. Fasting plasma glucose, lipids/lipoproteins, insulin and leptin levels were quantified, histopathologic score of hepatic steatosis and inflammation were assessed, and the responses of common checkpoints of insulin and leptin signalling responsible for lipogenesis and gluconeogenesis were analyzed. In addition, acute insulin or leptin administration was performed at different stages of HFHS dieting to determine the responsiveness of the respective signalling pathways. Hyperinsulinemia, hyperglycemia, dyslipidemia, and increased homeostasis model assessment of basal insulin resistance occurred 1-week after HFHS dieting, coinciding with upregulation of suppressor of cytokine signalling 3 in both hypothalamus and liver. However, hepatosteatosis, accompanied with increased expression of sterol regulatory element binding protein 1c and phosphoenolpyruvate carboxykinase, did not manifest until 4- to 8-week after HFHS dieting. Lowered insulin sensitivity (shown by decreased insulin receptor substrate 1 and protein kinase B phosphorylation) occurred approximately 2 weeks prior to leptin resistance (shown by impaired signal transducer and activator of transcription 3 activation) in both the liver and hypothalamus. Acute insulin/leptin administration also demonstrated the impaired insulin or leptin signalling transduction. These data suggest that lowered insulin sensitivity and leptin resistance occurred at least 2-3 weeks earlier than the manifestation of hepatosteatosis in rats fed HFHS diet. |
| Databáze: | OpenAIRE |
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