GLP-2 Dysregulates Hepatic Lipoprotein Metabolism, Inducing Fatty Liver and VLDL Overproduction in Male Hamsters and Mice
Autor: | Danielle Alvares, Laraib Ijaz, Jennifer Taher, Mahmood Hussain, Christopher A. Baker, Khosrow Adeli |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Very low-density lipoprotein Lipoproteins Gene Expression Lipoproteins VLDL Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Non-alcoholic Fatty Liver Disease Internal medicine Nonalcoholic fatty liver disease Glucagon-Like Peptide 2 medicine Animals Dyslipidemias Mice Knockout Mesocricetus Chemistry Lipogenesis digestive oral and skin physiology Fatty liver medicine.disease Fatty Liver 030104 developmental biology Liver Glucagon-Like Peptide-2 Receptor lipids (amino acids peptides and proteins) 030211 gastroenterology & hepatology Steatosis Dyslipidemia Lipoprotein |
Zdroj: | Endocrinology. 159:3340-3350 |
ISSN: | 1945-7170 |
Popis: | Fundamental complications of insulin resistance and type 2 diabetes include the development of nonalcoholic fatty liver disease and an atherogenic fasting dyslipidemic profile, primarily due to increases in hepatic very-low-density lipoprotein (VLDL) production. Recently, central glucagon-like peptide-2 receptor (GLP2R) signaling has been implicated in regulating hepatic insulin sensitivity; however, its role in hepatic lipid and lipoprotein metabolism is unknown. We investigated the role of glucagon-like peptide-2 (GLP-2) in regulating hepatic lipid and lipoprotein metabolism in Syrian golden hamsters, C57BL/6J mice, and Glp2r-/- mice consuming either a normal chow or high-fat diet (HFD). In the chow-fed hamsters, IP GLP-2 administration significantly increased fasting dyslipidemia, hepatic VLDL production, and the expression of key genes involved in hepatic de novo lipogenesis. In HFD-fed hamsters and chow-fed mice, GLP-2 administration exacerbated or induced hepatic lipid accumulation. HFD-fed Glp2r-/- mice displayed reduced glucose tolerance, VLDL secretion, and microsomal transfer protein lipid transfer activity, as well as exacerbated fatty liver. Thus, we conclude that GLP-2 plays a lipogenic role in the liver by increasing lipogenic gene expression and inducing hepatic steatosis, fasting dyslipidemia, and VLDL overproduction. In contrast, the lack of Glp2r appears to interfere with VLDL secretion, resulting in enhanced hepatic lipid accumulation. These studies have uncovered a role for GLP-2 in maintaining hepatic lipid and lipoprotein homeostasis. |
Databáze: | OpenAIRE |
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