Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice
نویسندگان
چکیده
منابع مشابه
Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.
Individuals with type 2 diabetes have an increased risk of atherosclerosis. One factor underlying this is dyslipidemia, which in hyperinsulinemic subjects with early type 2 diabetes is typically characterized by increased VLDL secretion but normal LDL cholesterol levels, possibly reflecting enhanced catabolism of LDL via hepatic LDLRs. Recent studies have also suggested that hepatic insulin sig...
متن کاملPlasma PCSK9 preferentially reduces liver LDL receptors in mice.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates the expression of LDL receptor (LDLR) protein. Gain-of-function mutations in PCSK9 cause hypercholesterolemia, and loss-of-function mutations result in lower plasma LDL-cholesterol. Here, we investigate the kinetics and metabolism of circulating PCSK9 relative to tissue levels of LDLRs. The administration...
متن کاملSecreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the proteinase K subfamily of subtilases that reduces the number of LDL receptors (LDLRs) in liver through an undefined posttranscriptional mechanism. We show that purified PCSK9 added to the medium of HepG2 cells reduces the number of cell-surface LDLRs in a dose- and time-dependent manner. This activity was approximately 10-...
متن کاملMechanisms and consequences of hepatic regulation of mTORC1 by metformin
Background In mammals, the ability to sense and respond to both intracellular and extracellular nutrient levels requires the integration and cooperation of multiple complex metabolic regulatory networks. Key among these are the mTOR and AMPK signaling pathways, which are activated in response to increased or decreased cellular energy levels, respectively. These pathways control cell growth, pro...
متن کاملPCSK9 deficiency unmasks a sex- and tissue-specific subcellular distribution of the LDL and VLDL receptors in mice.
Proprotein convertase subtilisin kexin type 9 (PCSK9), the last member of the family of Proprotein Convertases related to Subtilisin and Kexin, regulates LDL-cholesterol by promoting the endosomal/lysosomal degradation of the LDL receptor (LDLR). Herein, we show that the LDLR cell surface levels dramatically increase in the liver and pancreatic islets of PCSK9 KO male but not female mice. In co...
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ژورنال
عنوان ژورنال: Journal of Clinical Investigation
سال: 2012
ISSN: 0021-9738
DOI: 10.1172/jci61919