Abstract
Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules. Considering the wide biological processes in which sphingolipids are implicated, they have been associated with diseases that present abnormalities in their energetic metabolism, such as breast cancer. In this sense, sphingolipids could modulate various cell features, such as growth, proliferation, survival, senescence, and apoptosis in cancer progression; moreover, ceramide metabolism is associated to chemotherapy resistance, and regulation of metastasis. Cell–cell communication mediated by exosomes and lipoproteins has become relevant in the transport of several sphingolipids. Therefore, in this work we performed a comprehensive analysis of the state of the art about the multifaceted roles of ceramides, specifically the deregulation of ceramide metabolism pathways, being a key factor that could modulate neoplastic processes development. Under specific conditions, sphingolipids perform important functions in several cellular processes, and depending on the preponderant species and cellular and/or tissue status can inhibit or promote the development of metabolic and potentially breast cancer disease.
Highlights
A chronic excess of triglycerides in the body, within adipose tissue, can lead to its saturation and promote the release of free fatty acids (FFA) to blood circulation
TLR-4 by acid could a cascade of intracellular signaling and p65, by andphosphorylation the expression of IkBa, serin-palmitoyl acyltransferase (SPT), ceramide (CerS) and mediated which induces the activation of p50 and p65,synthase and the expression dihydroceramide desaturase, key(SPT), enzymes in the synthesis of ceramides
The phosphorylation of H2K dependent of Akt causes the translocation of H2K to the mitochondria-associated ER membranes (MAMs), wherein maintains interaction with voltage-dependent anion-selective channel 1 (VDAC-1), in this manner H2K takes advantage of the emerging ATP of the channel formed by VDAC-1, catalyzing the first reaction of glycolysis, in this way contributes to the Warburg effect [75], a metabolic adaptation to hypoxic microenvironment due to lack of blood supply, and fundamental in the survival neoplastic during early stages
Summary
A chronic excess of triglycerides in the body, within adipose tissue, can lead to its saturation and promote the release of free fatty acids (FFA) to blood circulation These lipids could be transported by serum albumin and lipoproteins, promoting their accumulation in tissues such as liver, pancreas, and skeletal muscle, which triggers alterations in several signaling pathways associated with energetic metabolism and cell cycle regulation [1]. TLR-4 by acid could a cascade of intracellular signaling and p65, by andphosphorylation the expression of IkBa, serin-palmitoyl acyltransferase (SPT), ceramide (CerS) and mediated which induces the activation of p50 and p65,synthase and the expression dihydroceramide desaturase, key(SPT), enzymes in the synthesis of ceramides [11]. Ceramides play important roles in the regulation of cancer progression, and are linked to their function in meta-inflammation, a condition that associates overnutrition and obesity with a chronic low-grade inflammatory state [21,22], representing a key factor in the regulation of pathological processes. In this work, we performed an analysis of the state of the art about the multifaceted role of ceramides in several pathological processes, with a focus on lipid metabolism and breast cancer
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