Short‐Term Statin Therapy Induces Hepatic Insulin Resistance Through HNF4α/PAQR9/PPM1α Axis Regulated AKT Phosphorylation

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 5, 2024

Abstract Statins, the first‐line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short‐term statin therapy on hyperlipidemia mice show that hepatic insulin resistance statin‐induced Statin raises expression progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits signaling through degradation protein phosphatase, Mg 2+ /Mn dependent 1 (PPM1 α ) activate ERK pathway. STIP1 homology U‐box containing (STUB1) found mediate ubiquitination PPM1 promoted by PAQR9. On other hand, decreased activity hepatocyte nuclear factor 4 alpha (HNF4 seems be PAQR9 under therapy. The interventions PAQR9, including deletion caloric restriction HNF4 activation, all effective treatments diabetes, while liver specific over‐expression another possible tactic. results reveal importance ‐PAQR9‐STUB1‐PPM1 axis controlling resistance, offering fresh insight into molecular mechanisms underlying

Язык: Английский

---

The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies

Metabolites, Год журнала: 2024, Номер 14(7), С. 388 - 388

Опубликована: Июль 17, 2024

Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, statins emerging the cornerstone treatment. These interventions play crucial role in both primary and secondary prevention by effectively reducing through lipid profile enhancements. Beyond their effects, extensive research indicates that these exhibit pleiotropic actions, offering additional benefits. include anti-inflammatory properties, improvements vascular glucose metabolism, potential implications cancer management. While ezetimibe been extensively studied, newer agents also demonstrate similar even absence of direct This narrative review explores diverse properties lipid-modifying therapies, emphasizing non-lipid effects contribute to burden exploring benefits for non-cardiovascular conditions. Mechanistic insights into actions are discussed alongside therapeutic implications.

Язык: Английский

---

Crosstalk between Statins and Cancer Prevention and Therapy: An Update

Pharmaceuticals, Год журнала: 2021, Номер 14(12), С. 1220 - 1220

Опубликована: Ноя. 25, 2021

The importance of statins in cancer has been discussed many studies. They are known for their anticancer properties against solid tumors the liver or lung, as well diffuse cancers, such multiple myeloma leukemia. Currently, most commonly used simvastatin, rosuvastatin and atorvastatin. anti-tumor activity is largely related to ability induce apoptosis by targeting cells with high selectivity. Statins also involved regulation histone acetylation level, disturbance which can lead abnormal genes proliferation, differentiation apoptosis. As a result, tumor growth its invasion may be promoted, associated poor prognosis. High levels deacetylases observed cancers; therefore, one therapeutic strategies use inhibitors. Combining deacetylase inhibitors synergistic effect.

Язык: Английский

---

Effects of treatment of non-alcoholic fatty liver disease on heart failure with preserved ejection fraction

Frontiers in Cardiovascular Medicine, Год журнала: 2023, Номер 9

Опубликована: Янв. 12, 2023

In the past few decades, non-alcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) have become most common chronic main form of (HF), respectively. NAFLD is closely associated HFpEF by sharing risk factors and/or boosting systemic inflammation, releasing other secretory factors, having an expansion epicardial adipose tissue (EAT). Therefore, treatments may also affect development prognosis HFpEF. However, no specific drugs for been approved Food Drug Administration (FDA) some non-specific are applied in clinic. Currently, can be divided into non-pharmacological pharmacological treatments. Non-pharmacological mainly include dietary intervention, weight loss exercise, caloric restriction, bariatric surgery. Pharmacological administering statins, thiazolidinediones, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin. This review will focus on analyzing how these

Язык: Английский

---

Statin Treatment Is Associated with Alterations in the Platelet Lipidome

Thrombosis and Haemostasis, Год журнала: 2023, Номер 123(06), С. 585 - 596

Опубликована: Март 10, 2023

Background Platelets are key players in the pathophysiology of coronary artery disease (CAD) and platelet hyperreactivity leads to increased risk developing adverse cardiovascular events. Further, significant changes lipidome occur patients with acute syndrome (ACS) critically regulated lipids lead hyperresponsiveness. Statin treatment is crucial prevention CAD by remodeling lipid metabolism. Objective In this study, we investigate untargeted lipidomics, highlighting between statin-treated naïve patients. Methods We characterized a cohort (n = 105) an lipidomics approach using liquid chromatography coupled mass spectrometry. Results Among annotated lipids, 41 were significantly upregulated patients, whereas 6 downregulated compared The most prominent belong class triglycerides, cholesteryl esters, palmitic acid, oxidized phospholipids, mainly glycerophospholipids untreated A more pronounced effect statin on was observed ACS further highlight dose-dependent influence lipidome. Conclusion Our results reveal that altered embody characteristic mostly compromise glycerophospholipids, which may play role CAD. study contribute understanding softening phenotype.

Язык: Английский

---