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Background: Cholesterol homeostasis in the human body is a crucial process that involves a delicate balance between dietary cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver. Both pathways contribute significantly to the overall pool of cholesterol in the body, influencing plasma cholesterol levels and impacting cardiovascular health. Elevated absorption of cholesterol in the intestines has a suppressive impact on the synthesis of cholesterol in the liver, serving to preserve cholesterol balance. Nonetheless, the precise mechanisms driving this phenomenon remain largely unclear.
Summary: This review aimed to discuss the previously unrecognized role of cholesin and GPR146 in the regulation of cholesterol biosynthesis, providing a novel conceptual framework for understanding cholesterol homeostasis.
Key Messages: The discovery of cholesin, a novel protein implicated in the regulation of cholesterol homeostasis, represents a significant advancement in our understanding of cholesterol biosynthesis and its associated pathways. The cholesin-GPR146 axis could have profound implications across various therapeutic areas concerning abnormal cholesterol metabolism, offering new hope for patients and improving overall healthcare outcomes.
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http://dx.doi.org/10.1159/000540351 | DOI Listing |
PLoS One
September 2025
Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
There is a lack of longitudinal data on type 2 diabetes (T2D) in low- and middle-income countries. We leveraged the electronic health records (EHR) system of a publicly funded academic institution to establish a retrospective cohort with longitudinal data to facilitate benchmarking, surveillance, and resource planning of a multi-ethnic T2D population in Malaysia. This cohort included 15,702 adults aged ≥ 18 years with T2D who received outpatient care (January 2002-December 2020) from Universiti Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America.
Background: Statin therapy lowers the risk of major adverse cardiovascular events (MACE) among people with HIV (PWH). Residual risk pathways contributing to excess MACE beyond low-density lipoprotein cholesterol (LDL-C) are not well understood. Our objective was to evaluate the association of statin responsive and other inflammatory and metabolic pathways to MACE in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).
View Article and Find Full Text PDFCNS Drugs
September 2025
Global Health Neurology Lab, Sydney, NSW, 2150, Australia.
Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline.
View Article and Find Full Text PDFMetabolomics
September 2025
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Introduction: Knockout of the Fmo5 gene in mice led to a lean, slow-ageing phenotype characterised by the presence of 2,3-butanediol isomers in their urine and plasma. Oral treatment of wildtype mice with 2,3-butanediol led to a low cholesterol, low epididymal fat phenotype.
Objectives: Determine if significant, heterozygous coding variations in human FMO5 would give rise to similar clinical and metabolic phenotypes in humans, as in C57BL/6J mice with knockout of the Fmo5 gene and in particular, increased excretion of 2,3-butanediol.
Eur Radiol
September 2025
Department of Ultrasound, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Objectives: To evaluate the predictive role of carotid stiffening, quantified using ultrafast pulse wave velocity (ufPWV), for assessing cardiovascular risk in young populations with no or elevated cardiovascular risk factors (CVRFs).
Materials And Methods: This study enrolled 180 young, apparently healthy individuals who underwent ufPWV measurements. They were classified into three groups: the CVRF-free group (n = 60), comprising current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.