-
1.
Therapeutic potential of melatonin in colorectal cancer: Focus on lipid metabolism and gut microbiota.
Pan, S, Guo, Y, Hong, F, Xu, P, Zhai, Y
Biochimica et biophysica acta. Molecular basis of disease. 2022;(1):166281
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. The occurrence and development of CRC are complicated processes. Obesity and dysbacteriosis have been increasingly regarded as the main risk factors for CRC. Understanding the etiology of CRC from multiple perspectives is conducive to screening for some potential drugs or new treatment strategies to limit the serious side effects of conventional treatment and prolong the survival of CRC patients. Melatonin, a natural indoleamine, is mainly produced by the pineal gland, but it is also abundant in other tissues, including the gastrointestinal tract, retina, testes, lymphocytes, and Harder's glands. Melatonin could participate in lipid metabolism by regulating adipogenesis and lipolysis. Additionally, many studies have focused on the potential beneficial effects of melatonin in CRC, such as promotion of apoptosis; inhibition of cell proliferation, migration, and invasion; antioxidant activity; and immune regulation. Meaningfully, gut microbiota is the main determinant of all aspects of health and disease (including obesity and tumorigenesis). The gut microbiota is of great significance for understanding the relationship between obesity and increased risk of CRC. Although the current understanding of how the melatonin-mediated gut microbiota coordinates a variety of physiological and pathological activities is fairly comprehensive, there are still many unknown topics to be explored in the face of a complex nutritional status and a changeable microbiota. This review summarizes the potential links among melatonin, lipid metabolism, gut microbiota, and CRC to promote the development of melatonin as a preventive and therapeutic agent for CRC.
-
2.
Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review.
Cano, R, Pérez, JL, Dávila, LA, Ortega, Á, Gómez, Y, Valero-Cedeño, NJ, Parra, H, Manzano, A, Véliz Castro, TI, Albornoz, MPD, et al
International journal of molecular sciences. 2021;(9)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.
-
3.
Ferroptosis: mechanisms and links with diseases.
Yan, HF, Zou, T, Tuo, QZ, Xu, S, Li, H, Belaidi, AA, Lei, P
Signal transduction and targeted therapy. 2021;(1):49
Abstract
Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.
-
4.
Lipids in regulating oligodendrocyte structure and function.
Montani, L
Seminars in cell & developmental biology. 2021;:114-122
Abstract
Oligodendrocytes enwrap central nervous system axons with myelin, a lipid enriched highly organized multi-layer membrane structure that allows for fast long-distance saltatory conduction of neuronal impulses. Myelin has an extremely high lipid content (∼80 % of its dry weight) and a peculiar lipid composition, with a 2:2:1 cholesterol:phospholipid:glycolipid ratio. Inherited neurodegenerative diseases of the lipids (caused by mutations in lipogenic enzymes) often present oligodendrocyte and/or myelin defects which contribute to the overall disease pathophysiology. These phenomena triggered an increasing number of studies over the functions lipid exert to shape and maintain myelin, and brought to the finding that lipids are more than only structural building blocks. They act as signaling molecules to drive proliferation and differentiation of oligodendrocyte progenitor cells, as well as proliferation of premyelinating oligodendrocytes, and their maturation into myelinating ones. Here, we summarize key findings in these areas, while presenting the main related human diseases. Despite many advances in the field, various questions remain open which we briefly discuss. This article is part of a special issue entitled "Role of Lipids in CNS Cell Physiology and Pathology".
-
5.
Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence.
Abdullah, MMH, Vazquez-Vidal, I, Baer, DJ, House, JD, Jones, PJH, Desmarchelier, C
Nutrients. 2021;(2)
Abstract
The number of nutrigenetic studies dedicated to the identification of single nucleotide polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has increased considerably over the last decade. However, the robustness of the evidence-based science supporting the area remains to be evaluated. The objective of this review was to present recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol metabolism and transport, and dietary intakes or interventions on circulating cholesterol concentrations, which are causally involved in cardiovascular diseases and established biomarkers of cardiovascular health. We identified recent studies (2014-2020) that reported significant SNP-diet interactions in 14 cholesterol-related genes (NPC1L1, ABCA1, ABCG5, ABCG8, APOA1, APOA2, APOA5, APOB, APOE, CETP, CYP7A1, DHCR7, LPL, and LIPC), and which replicated associations observed in previous studies. Some studies have also shown that combinations of SNPs could explain a higher proportion of variability in response to dietary interventions. Although some findings still need replication, including in larger and more diverse study populations, there is good evidence that some SNPs are consistently associated with differing circulating cholesterol concentrations in response to dietary interventions. These results could help clinicians provide patients with more personalized dietary recommendations, in order to lower their risk for cardiovascular disease.
-
6.
Towards Understanding the Direct and Indirect Actions of Growth Hormone in Controlling Hepatocyte Carbohydrate and Lipid Metabolism.
Vázquez-Borrego, MC, Del Rio-Moreno, M, Kineman, RD
Cells. 2021;(10)
Abstract
Growth hormone (GH) is critical for achieving normal structural growth. In addition, GH plays an important role in regulating metabolic function. GH acts through its GH receptor (GHR) to modulate the production and function of insulin-like growth factor 1 (IGF1) and insulin. GH, IGF1, and insulin act on multiple tissues to coordinate metabolic control in a context-specific manner. This review will specifically focus on our current understanding of the direct and indirect actions of GH to control liver (hepatocyte) carbohydrate and lipid metabolism in the context of normal fasting (sleep) and feeding (wake) cycles and in response to prolonged nutrient deprivation and excess. Caveats and challenges related to the model systems used and areas that require further investigation towards a clearer understanding of the role GH plays in metabolic health and disease are discussed.
-
7.
Cholesterol, lipoproteins, and COVID-19: Basic concepts and clinical applications.
Kočar, E, Režen, T, Rozman, D
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2021;(2):158849
-
-
Free full text
-
Abstract
Cholesterol is being recognized as a molecule involved in regulating the entry of the SARS-CoV-2 virus into the host cell. However, the data about the possible role of cholesterol carrying lipoproteins and their receptors in relation to infection are scarce and the connection of lipid-associated pathologies with COVID-19 disease is in its infancy. Herein we provide an overview of lipids and lipid metabolism in relation to COVID-19, with special attention on different forms of cholesterol. Cholesterol enriched lipid rafts represent a platform for viruses to enter the host cell by endocytosis. Generally, higher membrane cholesterol coincides with higher efficiency of COVID-19 entry. Inversely, patients with COVID-19 show lowered levels of blood cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins. The modulated efficiency of viral entry can be explained by availability of SR-B1 receptor. HDL seems to have a variety of roles, from being itself a scavenger for viruses, an immune modulator and mediator of viral entry. Due to inverse roles of membrane cholesterol and lipoprotein cholesterol in COVID-19 infected patients, treatment of these patients with cholesterol lowering statins needs more attention. In conclusion, cholesterol and lipoproteins are potential markers for monitoring the viral infection status, while the lipid metabolic pathways and the composition of membranes could be targeted to selectively inhibit the life cycle of the virus as a basis for antiviral therapy.
-
8.
Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19: A review.
Koriem, KMM
World journal of gastroenterology. 2021;(1):37-54
Abstract
The term lipidome is mentioned to the total amount of the lipids inside the biological cells. The lipid enters the human gastrointestinal tract through external source and internal source. The absorption pathway of lipids in the gastrointestinal tract has many ways; the 1st way, the lipid molecules are digested in the lumen before go through the enterocytes, digested products are re-esterified into complex lipid molecules. The 2nd way, the intracellular lipids are accumulated into lipoproteins (chylomicrons) which transport lipids throughout the whole body. The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are: (1) Transferred into the endoplasmic reticulum; (2) Collected as lipoproteins such as chylomicrons; or (3) Stored as lipid droplets in the cytosol. The lipids play an important role in many stages of the viral replication cycle. The specific lipid change occurs during viral infection in advanced viral replication cycle. There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection. The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity. The viral interest is cholesterol- and lipid raft-dependent molecules. In conclusion, lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019 (COVID-19) infection so lipidome is basic in gut metabolism and in COVID-19 infection success.
-
9.
Antioxidant and anti‑inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review).
Pereira, CPM, Souza, ACR, Vasconcelos, AR, Prado, PS, Name, JJ
International journal of molecular medicine. 2021;(1):37-48
-
-
Free full text
-
Abstract
Cardiovascular diseases are the most common cause of mortality worldwide. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases; thus, anti‑inflammatory and antioxidant agents that modulate redox balance have become research targets so as to evaluate their molecular mechanisms of action and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant properties due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also has prominent anti‑inflammatory activity, possibly interrelated with its antioxidant effect, and is also involved in the modulation of lipid and glucose metabolism. Considering the potential beneficial effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, the aim of the present review was to describe the molecular and cellular mechanisms associated with the antioxidant and anti‑inflammatory properties of this carotenoid in cardiovascular diseases, particularly atherosclerosis. The beneficial properties and safety profile of astaxanthin indicate that this compound may be used for preventing progression or as an adjuvant in the treatment of cardiovascular diseases.
-
10.
Integrating lipidomics and genomics: emerging tools to understand cardiovascular diseases.
Tabassum, R, Ripatti, S
Cellular and molecular life sciences : CMLS. 2021;(6):2565-2584
-
-
Free full text
-
Abstract
Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide leading to 31% of all global deaths. Early prediction and prevention could greatly reduce the enormous socio-economic burden posed by CVDs. Plasma lipids have been at the center stage of the prediction and prevention strategies for CVDs that have mostly relied on traditional lipids (total cholesterol, total triglycerides, HDL-C and LDL-C). The tremendous advancement in the field of lipidomics in last two decades has facilitated the research efforts to unravel the metabolic dysregulation in CVDs and their genetic determinants, enabling the understanding of pathophysiological mechanisms and identification of predictive biomarkers, beyond traditional lipids. This review presents an overview of the application of lipidomics in epidemiological and genetic studies and their contributions to the current understanding of the field. We review findings of these studies and discuss examples that demonstrates the potential of lipidomics in revealing new biology not captured by traditional lipids and lipoprotein measurements. The promising findings from these studies have raised new opportunities in the fields of personalized and predictive medicine for CVDs. The review further discusses prospects of integrating emerging genomics tools with the high-dimensional lipidome to move forward from the statistical associations towards biological understanding, therapeutic target development and risk prediction. We believe that integrating genomics with lipidome holds a great potential but further advancements in statistical and computational tools are needed to handle the high-dimensional and correlated lipidome.