Angiopoietin-like 4 (ANGPTL4) is critical for regulating plasma lipids, and thus an attractive therapeutic target for cardiovascular diseases. Unfortunately, targeting ANGPTL4 results in a proinflammatory and ultimately lethal phenotype in animals. The serendipitous discovery of cardiac ANGPTL4 as a circadian protein reveals novel mechanistic insight and a solution for this therapeutic dilemma.
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Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue.
Mol Metab
June 2022
Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address:
Objective: Brown adipose tissue (BAT) burns fatty acids (FAs) to produce heat, and shows diurnal oscillation in glucose and triglyceride (TG)-derived FA-uptake, peaking around wakening. Here we aimed to gain insight in the diurnal regulation of metabolic BAT activity.
Methods: RNA-sequencing, chromatin immunoprecipitation (ChIP)-sequencing, and lipidomics analyses were performed on BAT samples of wild type C57BL/6J mice collected at 3-hour intervals throughout the day.
The Mechanism of Oral Melatonin Ameliorates Intestinal and Adipose Lipid Dysmetabolism Through Reducing Escherichia Coli-Derived Lipopolysaccharide.
Cell Mol Gastroenterol Hepatol
March 2022
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. Electronic address:
Background & Aims: Gut microbiota have been reported to be sensitive to circadian rhythms and host lipometabolism, respectively. Although melatonin-mediated beneficial efforts on many physiological sites have been revealed, the regulatory actions of oral melatonin on the communication between gut microbiota and host are still not clear. Angiopoietin-like 4 (ANGPTL4) has been shown to be strongly responsible for the regulation of systemic lipid metabolism.
View Article and Find Full Text PDFCircadian Angiopoietin-Like-4 as a Novel Therapy in Cardiovascular Disease.
Trends Mol Med
July 2021
Department of Anesthesiology, University of Colorado Denver School of Medicine, Aurora, CO, USA; Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Cell and Developmental Biology, University of Colorado Denver School of Medicine, Aurora, CO, USA. Electronic address:
Angiopoietin-like 4 (ANGPTL4) is critical for regulating plasma lipids, and thus an attractive therapeutic target for cardiovascular diseases. Unfortunately, targeting ANGPTL4 results in a proinflammatory and ultimately lethal phenotype in animals. The serendipitous discovery of cardiac ANGPTL4 as a circadian protein reveals novel mechanistic insight and a solution for this therapeutic dilemma.
View Article and Find Full Text PDFA Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening.
Cell Rep
March 2018
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism.
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