Improvement of non-invasive tests of liver steatosis and fibrosis as indicators for non-alcoholic fatty liver disease in type 2 diabetes mellitus patients with elevated cardiovascular risk profile using the PPAR-α/γ agonist aleglitazar

Grobbee, Esmée J.; Jong, Vivian D. de; Schrieks, Ilse C.; Tushuizen, Maarten E.; Holleboom, Adriaan G.; Tardif, Jean‐Claude; Lincoff, A. Michael; Schwartz, Gregory G.; Cabezas, Manuel Castro; Grobbee, Diederick E.

doi:10.1371/journal.pone.0277706

Cited by 4 publications

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several drugs have been developed to target multiple receptor subtypes rather than one, including the PPARα/PPARγ agonists saroglitazar and aleglitazar, the PPARα/PPARδ agonist elafibranor, and the pan‐PPAR agonist lanifibranor. All of them are being investigated in patients with NAFLD in clinical trials 279–282 …”

Section: The Role Of Macrophages In Diseases and Targeted Therapiesmentioning

confidence: 99%

Signaling pathways in macrophages: molecular mechanisms and therapeutic targets

Li,

Wang,

Wen

et al. 2023

MedComm

View full text Add to dashboard Cite

Macrophages play diverse roles in development, homeostasis, and immunity. Accordingly, the dysfunction of macrophages is involved in the occurrence and progression of various diseases, such as coronavirus disease 2019 and atherosclerosis. The protective or pathogenic effect that macrophages exert in different conditions largely depends on their functional plasticity, which is regulated via signal transduction such as Janus kinase–signal transducer and activator of transcription, Wnt and Notch pathways, stimulated by environmental cues. Over the past few decades, the molecular mechanisms of signaling pathways in macrophages have been gradually elucidated, providing more alternative therapeutic targets for diseases treatment. Here, we provide an overview of the basic physiology of macrophages and expound the regulatory pathways within them. We also address the crucial role macrophages play in the pathogenesis of diseases, including autoimmune, neurodegenerative, metabolic, infectious diseases, and cancer, with a focus on advances in macrophage‐targeted strategies exploring modulation of components and regulators of signaling pathways. Last, we discuss the challenges and possible solutions of macrophage‐targeted therapy in clinical applications. We hope that this comprehensive review will provide directions for further research on therapeutic strategies targeting macrophage signaling pathways, which are promising to improve the efficacy of disease treatment.

show abstract

Section: The Role Of Macrophages In Diseases and Targeted Therapiesmentioning

confidence: 99%

Signaling pathways in macrophages: molecular mechanisms and therapeutic targets

Li,

Wang,

Wen

et al. 2023

MedComm

View full text Add to dashboard Cite

show abstract

“…In preclinical studies of Apoe −/− mice on a high-fat/high-cholesterol diet, the dual PPARα/γ agonist aleglitazar improved glucose tolerance and lowered hepatic fat content without an increase in body weight [ 136 ]. In the AleCardio trial, aleglitazar reduced hepatic steatosis and fibrosis in subjects with acute coronary syndrome and type 2 diabetes mellitus [ 137 ]. Saroglitazar, another dual PPARα/γ agonist, showed similar benefits in mouse models of NAFLD/NASH [ 138 ] and in a recent phase 2 clinical trial [ 139 ].…”

Section: Treatment Modalitiesmentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease: Translating Disease Mechanisms into Therapeutics Using Animal Models

Basha

May

Anderson

et al. 2023

IJMS

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is a range of pathologies arising from fat accumulation in the liver in the absence of excess alcohol use or other causes of liver disease. Its complications include cirrhosis and liver failure, hepatocellular carcinoma, and eventual death. NAFLD is the most common cause of liver disease globally and is estimated to affect nearly one-third of individuals in the United States. Despite knowledge that the incidence and prevalence of NAFLD are increasing, the pathophysiology of the disease and its progression to cirrhosis remain insufficiently understood. The molecular pathogenesis of NAFLD involves insulin resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. Better insight into these molecular pathways would allow for therapies that target specific stages of NAFLD. Preclinical animal models have aided in defining these mechanisms and have served as platforms for screening and testing of potential therapeutic approaches. In this review, we will discuss the cellular and molecular mechanisms thought to contribute to NAFLD, with a focus on the role of animal models in elucidating these mechanisms and in developing therapies.

show abstract