Archives of Physiology and Biochemistry, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 9
Published: Nov. 14, 2024
The impact of triglyceride levels is important to understand the changes in metabolism and structure. With an increase obesity hyperlipidemia due diet; cardiovascular neuronal structural have been shown be more distinct.
Language: Английский
Journal of Lipid and Atherosclerosis, Journal Year: 2024, Volume and Issue: 13(1), P. 2 - 2
Published: Jan. 1, 2024
Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase may influence the secretion uptake of various lipoproteins. Genetic studies show that depletion these proteins is associated with improved lipid profiles reduced cardiovascular events so it was anticipated drugs which mimic effects loss-of-function mutations would be useful treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), usually not adequately controlled currently available drugs. However, found also effective in reducing low-density cholesterol (LDL-C) they studied patients homozygous hypercholesterolaemia (FH). Evinacumab targets LDL-C about 50% FH has been approved indication. The antisense oligonucleotide (ASO) vupanorsen targeting less moderate its development discontinued but small interfering RNA (siRNA) ARO-ANG3 being investigated Phase 2 studies. ApoC3 can inhibited ASO volanesorsen, triglycerides >70% FCS Europe United States because concerns thrombocytopaenia. Olezarsen an N-acetylgalactosamine-conjugated apoC3 appears volanesorsen without risk thrombocytopaenia undergoing trials. ARO-APOC3 siRNA
Language: Английский
Citations
18
Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14
Published: Jan. 18, 2024
Since statins have had such tremendous therapeutic success over the last three decades, field of atherosclerosis has become somewhat LDL-centric, dismissing relevance triglycerides (TG), particularly chylomicrons, in atherogenesis. Nonetheless, 50% patients who take are at risk developing atherosclerotic cardiovascular disease (ASCVD) and unable to achieve their goal LDL-C levels. This residual is mediated, part by triglyceride rich lipoproteins (TRL) remnants. Following his seminal investigation on subject, Zilversmit proposed that a postprandial event 1979 (1–4). In essence, concept suggests remnant cholesterol-rich chylomicron (CM) very-low density lipoprotein (VLDL) particles play role Given foregoing, this narrative review addresses most recent improvements our understanding dyslipidemia. The primary metabolic pathways chylomicrons discussed, emphasizing critical physiological lipase apoCIII, importance these particles’ fluxes period, catabolic rate, complexities testing metabolism, angiopoietin-like proteins partition CM during fed cycle. rounded out dysregulation lipid metabolism insulin resistance states consequent CVD risk, clinical evaluation dyslipidemia, current research limits, potential future study directions.
Language: Английский
Citations
13
Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(6), P. 490 - 504
Published: March 23, 2024
The regulation of triglyceride (TG) tissue distribution, storage, and utilization, a fundamental process energy homeostasis, critically depends on lipoprotein lipase (LPL). We review the intricate mechanisms by which LPL activity is regulated angiopoietin-like proteins (ANGPTL3, 4, 8), apolipoproteins (APOA5, APOC3, APOC2), cAMP-responsive element-binding protein H (CREBH). ANGPTL8 functions as molecular switch, through complex formation, activating ANGPTL3 while deactivating ANGPTL4 in their inhibition. ANGPTL3-4-8 model integrates roles aforementioned TG partitioning between white adipose (WAT) oxidative tissues (heart skeletal muscles) during feed/fast cycle. This offers unified perspective regulation, providing insights into metabolism, metabolic diseases, therapeutics.
Language: Английский
Citations
11
American Journal of Preventive Cardiology, Journal Year: 2024, Volume and Issue: 18, P. 100648 - 100648
Published: March 23, 2024
Triglycerides play a crucial role in the efficient storage of energy body. Mild and moderate hypertriglyceridemia (HTG) is heterogeneous disorder with significant association atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, peripheral artery represents an important component residual ASCVD risk statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have incremental incidence acute pancreatitis morbidity mortality. can occur from combination genetic (both mono polygenic) environmental factors poor diet, low physical activity, obesity, medications, diseases like insulin resistance other endocrine pathologies. potential target for reduction, however data on reduction by treating still lacking HTG-associated occurs too to effectively demonstrate treatment benefit. In this review, we address key aspects pathophysiology examine mechanisms background current emerging therapies management HTG.
Language: Английский
Citations
9
Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15
Published: May 31, 2024
The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause mortality worldwide. Atherosclerosis (AS) serves as primary driver these conditions, commencing silently at an early age and culminating in adverse events that severely impact patients’ quality life or lead fatality. Dyslipidemia, particularly elevated levels low-density lipoprotein cholesterol (LDL-C), plays pivotal role AS pathogenesis independent risk factor. Research indicates abnormal LDL-C accumulation within arterial walls acts crucial trigger for atherosclerotic plaque formation. As the disease progresses, may rupture dislodge, resulting thrombus formation complete blood supply obstruction, ultimately causing myocardial infarction, cerebral other common events. Despite adequate pharmacologic therapy targeting reduction, patients with cardiometabolic abnormalities remain high recurrence, highlighting importance addressing lipid factors beyond LDL-C. Recent attention has focused on causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), their remnants risk. Genetic, epidemiologic, clinical studies suggest TRLs increased AS, this dyslipidemia be factor Particularly obesity, metabolic syndrome, diabetes, chronic kidney disease, disordered its significantly increase atherosclerosis development. Accumulation over-synthesized plasma, impaired function enzymes involved lipolysis, hepatic clearance cholesterol-rich can deposition remnants, promoting foam cell wall inflammation. Therefore, understanding TRLs-induced therapeutically could slow impede progression, thereby reducing morbidity mortality, coronary heart disease.
Language: Английский
Citations
9
Nutrients, Journal Year: 2024, Volume and Issue: 16(15), P. 2453 - 2453
Published: July 28, 2024
Functional lipids are dietary substances that may have an impact on human health by lowering the risk of chronic illnesses and enhancing quality life. Numerous functional been reported to potential benefits in prevention, management, treatment cardiovascular disease, leading cause death United States. However, there is still insufficient contradictory information literature about their effectiveness associated mechanisms action. The objective this review, therefore, evaluate available regarding these benefits. Various studies conducted understand links between prevention diseases. Recent phytosterols CLA, medium-chain triglycerides, omega-3 6 fatty acids positive effects health. Also, eicosanoids, which metabolites acids, produced relation ratio omega-6 polyunsaturated modulate disease conditions. These either or supplement forms proven be efficient, accessible, inexpensive included diet. further research required properly elucidate dosages, intake, effectiveness, action addition development valid biomarkers long-term humans.
Language: Английский
Citations
9
Food & medicine homology., Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
1
Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 29, 2025
Language: Английский
Citations
0
Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown
Published: March 14, 2025
Abstract Aims To investigate the associations of intra‐pancreatic fat deposition (IPFD) with very‐low‐density lipoprotein (VLDL), intermediate‐density (IDL) and lipase. Materials methods A total 174 participants underwent magnetic resonance imaging on a 3.0 Tesla scanner for quantification IPFD. Blood samples were collected following an 8‐h fasting period. Triglyceride‐rich lipoproteins measured using Lipoprint® system classed as VLDL, IDL‐C, IDL‐B IDL‐A subfractions. Lipoprotein lipase was ELISA. Univariable multivariable linear regression analyses conducted. Results Both IPFD significantly associated levels in most adjusted model. Specifically, each unit increase 0.12‐unit ( p = 0.047) whereas 0.22‐unit 0.015). Neither nor VLDL. Conclusions The relationship triglyceride‐rich differs depending nature lipoproteins. High is increased IDL (specifically, its representative subfraction—IDL‐B), but not Fatty pancreas disease may contribute to increasing risk atherosclerotic CVD through IDL.
Language: Английский
Citations
0
Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)
Published: March 20, 2025
Lipoprotein lipase (LPL) carries out the lipolytic processing of triglyceride-rich lipoproteins (TRL) along luminal surface capillaries. LPL activity is regulated by angiopoietin-like proteins (ANGPTL3, ANGPTL4, ANGPTL8), which control delivery TRL-derived lipid nutrients to tissues in a temporal and spatial fashion. This regulation mediates partitioning adipose tissue striated muscle according nutritional status. A complex between ANGPTL3 ANGPTL8 (ANGPTL3/8) inhibits oxidative tissues, but its mode action has remained unknown. Here, we used biophysical techniques define how ANGPTL3/8 interact with they drive inactivation. We demonstrate, mass photometry, that heterotrimer 2:1 ANGPTL3:ANGPTL8 stoichiometry homotrimer. Hydrogen–deuterium exchange spectrometry (HDX-MS) studies revealed use proximal portion their N-terminal α-helices sequences surrounding catalytic pocket LPL. That binding event triggers unfolding LPL’s α/β -hydrolase domain irreversible loss activity. The endothelial transporter protein (GPIHBP1) or heparan-sulfate proteoglycans protects from inactivation, particularly against triggered ANGPTL3. Pulse-labeling HDX-MS catalyze an ATP-independent fashion, categorizes these inhibitors as atypical unfoldases. nature explains why low plasma concentrations are effective inhibiting molar excess
Language: Английский
Citations
0