Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways

Abstract

Glycolipid metabolic disorders (GLMDs) are various metabolic disorders resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake and a lack of physical activity may contribute to oxidative stress (OxS) and systemic inflammation. This study aimed to review the connection between GLMD, OxS, metainflammation, and the onset of CRVD. GLMD is due to various metabolic disorders causing dysfunction in the synthesis, breakdown, and absorption of glucose and lipids in the body, resulting in excessive ectopic accumulation of these molecules. This is mainly due to neuroendocrine dysregulation, insulin resistance, OxS, and metainflammation. In GLMD, many inflammatory markers and defense cells play a vital role in related tissues and organs, such as blood vessels, pancreatic islets, the liver, muscle, the kidneys, and adipocytes, promoting inflammatory lesions that affect various interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, and sphingosine-1-phosphate (S1P) play a crucial role in GLMD since they are related to glucolipid metabolism. The consequences of this is system organ damage and increased morbidity and mortality.

Keywords: atherogenesis; cardiovascular diseases; dyslipidemia; glycolipid metabolic disorders; hyperglycemia; metainflammation; oxidative stress.

Figure 1

Glycolipid metabolic disorders are related to unhealthy habits, leading to alterations in the body’s metabolism, initiating inflammatory processes and oxidative stress, and leading to several metabolic conditions such as insulin resistance, diabetes, obesity, metabolic syndrome, and CVD. In summary, this image makes explicit the systemic aggression and its complications. CVD: cardiovascular disease; hs-CRP: hs-C reactive protein; IFN-γ: Interferon-γ; TNF-α: tumor necrosis factor-α.

Figure 2

The relationship between chemical mediators in glycolipid metabolic disorders and the affected systems. The imbalance in glycolipids promotes a systemic inflammatory storm, which can lead to CVD, hormone diseases, and gastrointestinal disorders. ACE-2: Angiotensin-converting enzyme 2; ABCA1: ATP-binding cassette transporter; CVD: cardiovascular disease; GLP-1: Glucagon-like peptide-1; MAFLD: metabolic-associated fatty liver disease; SIP: sphingosine-1-phosphate; TLR4: Toll-like 1296 receptor-4; VNN1: vascular non-inflammatory molecule-1.

Figure 3

Hyperglycemia is related to the production of AGES. These reactive compounds are related to several metabolic conditions. The increase in unhealthy food intake triggers a rich inflammatory environment, which can result in changes in DNA, protein modifications, insulin resistance, oxidative stress, and inflammation that can be related with several conditions such as obesity, diabetes, metabolic syndrome, and liver, kidney, degenerative, and cardiovascular diseases. AGES: advanced glycation end products; IL-6: Interleukine-6; IL-1β: Interleukine-1β; IF-γ: Interferon-γ; ox-LDL: oxidized low-density lipoprotein; TNF-α: tumor necrosis factor-α; WAT: white adipose tissue.

Figure 4

Interconnections between oxidative stress and inflammation. The persistent and systemic low-grade inflammation known as metabolic inflammation or metainflammation plays a fundamental role in the pathogenesis and aggravation of metabolic diseases, such as diabetes and cardiovascular diseases. The principal mechanism is through the disfunction of cytokines with an excess of her productions. The changes in the secretory pattern can worsen glycolipid disorders, and finally, 1314 maintains the metainflammatory metabolism. IL-1β: Interleukine-1β; IL-6: Interleukine1315 6; IL-10: Interleukine-10; INF-γ: Interferon-γ; NF-kβ: Nuclear factor kappa β; NO: nitric oxide; ROS: reactive oxygen species; TGF-β: Transforming Growing Factor-β; 1317 TNF-α: tumor necrosis factor-α.

Figure 5

The physiopathology of atheroma’s plaque is closely associated with glucolipid metabolic disorders. Increased circulating lipids and oxidation promoted by free radicals can initiate plaque formation. Endothelial dysfunction occurs and oxLDL-c are recognized and phagocytosed by macrophages, leading to the formation of foam cells. The next steps are related to the initiation and progression of the atherosclerotic plaque that can occlude the arteries. ICAM-1: intercellular adhesion molecule-1; ICAM-2: intercellular adhesion molecule-2; IL-6: Interleukin-6; ox-LDL: oxidized low-density lipoprotein; MPC-1: monocyte chemoattractant peptide-1; TNF-α: tumor necrosis 1327 factor-α; VCAM-1: vascular cell adhesion molecule-1.

Figure 6

Higher chronic consumption of sodium promotes malefic changes in the nervous system and many alterations in the vascular endothelium. Firstly, the activation of the renin–angiotensin–aldosterone system occurs to equal the osmotic concentration in the blood increasing the blood pressure. Furthermore, the unhealthy food habits promote issues in vascular tunica intima, leading to the secretion and accumulation of inflammatory cells and cytokines in the vessels, resulting in atherosclerosis. In addition, the higher lipid concentration creates difficulty for the signaling of insulin receptors, promoting insulin resistance. Finally, all of these changes are connected with metabolic syndrome and other cardiovascular issues. ICAM-1: intercellular adhesion molecule-1; ICAM-2: intercellular adhesion molecule-2; IL-6: Interleukin-6; MPC-12: monocyte chemoattractant peptide-12; ox-LDL: oxidized low-density lipoprotein; TNF-α: tumor necrosis factor-α; VCAM-1: vascular cell adhesion molecule-1.