VLDL Biogenesis and Secretion: It Takes a Village
2024/01/18 by Willemien van Zwol, Bart van de Sluis, Henry N. Ginsberg +1 · 29 citations
Medicine · #Liver Disease Diagnosis and Treatment #Lipid metabolism and disorders #Diet, Metabolism, and Disease
paper · doi:10.1161/circresaha.123.323284
Abstract
The production and secretion of VLDLs (very-low-density lipoproteins) by hepatocytes has a direct impact on liver fat content, as well as the concentrations of cholesterol and triglycerides in the circulation and thus affects both liver and cardiovascular health, respectively. Importantly, insulin resistance, excess caloric intake, and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased plasma levels of atherogenic lipoproteins. Cholesterol and triglycerides in remnant particles generated by VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease and have garnered increasing attention over the last few decades. Presently, however, increased risk of atherosclerosis is not the only concern when considering today's cardiometabolic patients, as they often also experience hepatic steatosis, a prevalent disorder that can progress to steatohepatitis and cirrhosis. This duality of metabolic risk highlights the importance of understanding the molecular regulation of the biogenesis of VLDL, the lipoprotein that transports triglycerides and cholesterol out of the liver. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, which has led to many exciting new molecular insights that are the topic of this review. Increasing our understanding of the biology of this pathway will aid to the identification of novel therapeutic targets to improve both the cardiovascular and the hepatic health of cardiometabolic patients. This review focuses, for the first time, on this duality.
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- Gene Therapy for Inherited Liver Disease: To Add or to Edit. [europepmc]
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- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease. [europepmc]
- Association between triglyceride glucose-waist-adjusted waist index and incident stroke in Chinese adults: a prospective cohort study. [europepmc]
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective. [europepmc]
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- Regulatory effects of hawthorn on lipid metabolic homeostasis: mechanisms, evidences, and perspectives. [europepmc]
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- Current and Emerging Pharmacological Therapies for Hypertriglyceridemia. [europepmc]
- Epigallocatechin gallate and lipid metabolism: intestinal fate, metabolite clusters, and regulatory mechanisms. [europepmc]
- Influence of Tectona grandis leaf supplementation on growth, nutrient digestibility, serum biochemistry, hepatic antioxidant status, and cecal microbial profile in rabbits. [europepmc]
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease. [europepmc]
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