HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome
Abstract
:1. The Metabolic Syndrome: Epidemiology and Introduction
2. TG and HDL Biogenesis
3. Understanding HDL: Insights into Functional and Dysfunctional Particles
3.1. HDL Particles: Structure and Composition
3.2. Functional HDL Particles
3.2.1. Antioxidant Properties
3.2.2. Vasodilatory and Antithrombotic Properties
3.2.3. Glucose Metabolism
3.2.4. Others
3.3. HDL Adverse Remodelling: The Impact of Cardiovascular Risk Factors and Comorbid Conditions in HDL Functionality
4. The Role of TG and FFAA in Metabolic and Cardiovascular Risk
4.1. FFAA and Lipid Metabolism: TG-Rich Lipoproteins and Remnant Lipoprotein Particles
4.2. FFAA and Glucose Control
4.3. FFAA Levels and the Vascular Tone
5. The TG/HDL-C Ratio
6. Therapeutic Management to Target TG and HDL-C Levels
6.1. Lifestyle Changes
6.2. Drug Therapy
6.2.1. Effort to Improve Primary Cardiovascular Endpoints by Increasing HDL-C Levels or HDL-Mimetics
6.2.2. Others Therapeutic Strategies
7. Future Perspectives and Directions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ABCA1 | ATP-binding cassette protein A1 |
ABCG1 | ATP-binding cassette protein G1 |
Apo | apolipoprotein |
CAD | coronary artery disease |
CE | cholesterol esters |
CETP | cholesteryl ester transfer protein |
CVD | cardiovascular disease |
EVOO | extra virgin olive oil |
FFAA | free fatty acids |
FoxO1 | forkhead box protein O1 |
HDL | high-density lipoproteins |
IDL | intermediate-density lipoproteins |
IR | insulin resistance |
LCAT | lecithin–cholesterol acyltransferase |
LDL | low-density lipoproteins |
LDLR | LDL receptor |
MetS | metabolic syndrome |
MUFA | mono-saturated fatty acids |
NO | nitric oxide |
PL | phospholipids |
RAAS | renin–angiotensin–aldosterone system |
RCT | reverse cholesterol transport |
RISK | reperfusion injury signaling kinase |
RLP | remnant lipoprotein particles |
ROS | reactive oxygen species |
SAFE | survivor activating factor enhancement |
S1P | sphingosine-1-phosphate |
SR-BI | scavenger receptor class B type I |
TG | triglycerides |
TRL | TG-rich lipoprotein |
VCAM-1 | vascular cell adhesion molecule-1 |
VLDL | very low-density lipoproteins |
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Drug Class | Example(s) | Doses (Oral) | Clinical Indications (Type of Patients) | Positive Outcomes | Clinical Outcomes | Reference |
---|---|---|---|---|---|---|
Vitamin B3 | Niacin | 500–2000 mg/d | CVD, MetS | ↑HDL by ~15–30%, ↓TG by ~20–50% | No effect or ↓CV events | [217,218,219] |
CETP Inhibitors | Dalcetrapib; | 600 mg/d | Recent acute coronary syndrome; | ↑HDL by ~31–40%; no significant ↓TG; | No significant ↓CV events; | [220] |
Evacetrapib; | 130 mg/d | Acute coronary syndrome, cerebrovascular disease, T2DM with CVD; | ↑HDL by ~130%, ↓TG by ~6%; | No significant ↓CV events; | [221] | |
Torceratrip | 60 mg/d | High CV risk; | ↑HDL by ~72%, ↓TG by ~10%; | ↑CV events, ↑death; | [222] | |
Anacetrapib | 100 mg/d | High CVD risk, low HDL levels | ↑HDL by ~145%, ↓TG by ~9% | ↓CV events (men) | [223] | |
Omega-3 Fatty Acids | IPE | 4 g/d | High CV risk or T2DM | ↑HDL by ~3%, ↓TG by ~20% | ↓CV events | [224] |
EPA + DHA | 4 g/d | High risk of CVD with low HDL, elevated TG | ↑HDL by ~5%, ↓TG by ~19% | No significant ↓MACE | [225] | |
Fibrates | Fenofibrate | 200 mg/d | T2DM | ↑HDL by ~5%, ↓TG by ~29% | No significant ↓primary outcome | [226] |
Gemfibrozil | 1200 mg/d | CVD, low HDL, elevated TG | ↑HDL by ~6%, ↓TG by ~31% | ↓MACE | [227] | |
Statin + Fibrate | Simvastatin + Fenofibrate | 40 + 160 mg/d | Low HDL, high TG | ↑HDL by ~8%, ↓TG by ~26% | No significant ↓primary outcome | [228] |
Thiazolidinediones | Pioglitazone | 15–45 mg/d, | T2DM with CVD | ↑HDL by ~19%, ↓TG by ~11% | ↓CV events, ↓death | [229] |
Statins | Rosuvastatin | 20 mg/d | High CV risk | No significant ↑HDL, ↓TG by ~19% | ↓MACE | [230] |
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Alcover, S.; Ramos-Regalado, L.; Girón, G.; Muñoz-García, N.; Vilahur, G. HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome. Antioxidants 2025, 14, 434. https://doi.org/10.3390/antiox14040434
Alcover S, Ramos-Regalado L, Girón G, Muñoz-García N, Vilahur G. HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome. Antioxidants. 2025; 14(4):434. https://doi.org/10.3390/antiox14040434
Chicago/Turabian StyleAlcover, Sebastià, Lisaidy Ramos-Regalado, Gabriela Girón, Natàlia Muñoz-García, and Gemma Vilahur. 2025. "HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome" Antioxidants 14, no. 4: 434. https://doi.org/10.3390/antiox14040434
APA StyleAlcover, S., Ramos-Regalado, L., Girón, G., Muñoz-García, N., & Vilahur, G. (2025). HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome. Antioxidants, 14(4), 434. https://doi.org/10.3390/antiox14040434