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The Journal of Experimental Medicine Jan 2021Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for... (Review)
Review
Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.
Topics: Animals; Cell Proliferation; Humans; Immunotherapy; Lipid Metabolism; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 33601415
DOI: 10.1084/jem.20201606 -
Reviews in Endocrine & Metabolic... Dec 2019The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet properties such as the... (Review)
Review
The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet properties such as the amount and composition of lipids. Hence, dietary lipids may influence host physiology through interaction with the gut microbiota. Lipids affect the gut microbiota both as substrates for bacterial metabolic processes, and by inhibiting bacterial growth by toxic influence. The gut microbiota has been shown to affect lipid metabolism and lipid levels in blood and tissues, both in mice and humans. Furthermore, diseases linked to dyslipidemia, such as non-alcoholic liver disease and atherosclerosis, are associated with changes in gut microbiota profile. The influence of the gut microbiota on host lipid metabolism may be mediated through metabolites produced by the gut microbiota such as short-chain fatty acids, secondary bile acids and trimethylamine and by pro-inflammatory bacterially derived factors such as lipopolysaccharide. Here we will review the association between gut microbiota, dietary lipids and lipid metabolism.
Topics: Animals; Bile Acids and Salts; Gastrointestinal Microbiome; Humans; Lipid Metabolism; Lipids; Methylamines
PubMed: 31707624
DOI: 10.1007/s11154-019-09512-0 -
Nature Reviews. Molecular Cell Biology Jun 2021In animals, systemic control of metabolism is conducted by metabolic tissues and relies on the regulated circulation of a plethora of molecules, such as hormones and... (Review)
Review
In animals, systemic control of metabolism is conducted by metabolic tissues and relies on the regulated circulation of a plethora of molecules, such as hormones and lipoprotein complexes. MicroRNAs (miRNAs) are a family of post-transcriptional gene repressors that are present throughout the animal kingdom and have been widely associated with the regulation of gene expression in various contexts, including virtually all aspects of systemic control of metabolism. Here we focus on glucose and lipid metabolism and review current knowledge of the role of miRNAs in their systemic regulation. We survey miRNA-mediated regulation of healthy metabolism as well as the contribution of miRNAs to metabolic dysfunction in disease, particularly diabetes, obesity and liver disease. Although most miRNAs act on the tissue they are produced in, it is now well established that miRNAs can also circulate in bodily fluids, including their intercellular transport by extracellular vesicles, and we discuss the role of such extracellular miRNAs in systemic metabolic control and as potential biomarkers of metabolic status and metabolic disease.
Topics: Animals; Glucose; Humans; Lipid Metabolism; Metabolic Diseases; MicroRNAs
PubMed: 33772227
DOI: 10.1038/s41580-021-00354-w -
Cancer Communications (London, England) May 2018Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and... (Review)
Review
Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth. SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor, thus linking glucose metabolism and de novo lipid synthesis. Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.
Topics: Animals; Antineoplastic Agents; Endoplasmic Reticulum; Humans; Intracellular Signaling Peptides and Proteins; Lipid Metabolism; Lipogenesis; Membrane Proteins; Models, Biological; Neoplasms; Sterol Regulatory Element Binding Proteins
PubMed: 29784041
DOI: 10.1186/s40880-018-0301-4 -
Cell Metabolism Aug 2013Cancer cells often have characteristic changes in metabolism. Cellular proliferation, a common feature of all cancers, requires fatty acids for synthesis of membranes... (Review)
Review
Cancer cells often have characteristic changes in metabolism. Cellular proliferation, a common feature of all cancers, requires fatty acids for synthesis of membranes and signaling molecules. Here, we provide a view of cancer cell metabolism from a lipid perspective, and we summarize evidence that limiting fatty acid availability can control cancer cell proliferation.
Topics: Cell Proliferation; Energy Metabolism; Fatty Acids; Humans; Lipid Metabolism; Neoplasms
PubMed: 23791484
DOI: 10.1016/j.cmet.2013.05.017 -
Comprehensive Physiology Dec 2017Triglyceride molecules represent the major form of storage and transport of fatty acids within cells and in the plasma. The liver is the central organ for fatty acid... (Review)
Review
Triglyceride molecules represent the major form of storage and transport of fatty acids within cells and in the plasma. The liver is the central organ for fatty acid metabolism. Fatty acids accrue in liver by hepatocellular uptake from the plasma and by de novo biosynthesis. Fatty acids are eliminated by oxidation within the cell or by secretion into the plasma within triglyceride-rich very low-density lipoproteins. Notwithstanding high fluxes through these pathways, under normal circumstances the liver stores only small amounts of fatty acids as triglycerides. In the setting of overnutrition and obesity, hepatic fatty acid metabolism is altered, commonly leading to the accumulation of triglycerides within hepatocytes, and to a clinical condition known as nonalcoholic fatty liver disease (NAFLD). In this review, we describe the current understanding of fatty acid and triglyceride metabolism in the liver and its regulation in health and disease, identifying potential directions for future research. Advances in understanding the molecular mechanisms underlying the hepatic fat accumulation are critical to the development of targeted therapies for NAFLD. © 2018 American Physiological Society. Compr Physiol 8:1-22, 2018.
Topics: Biological Transport; Fatty Acids; Humans; Lipid Metabolism; Lipogenesis; Lipolysis; Liver; Non-alcoholic Fatty Liver Disease; Triglycerides
PubMed: 29357123
DOI: 10.1002/cphy.c170012 -
Journal of Lipid Research Apr 2020Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic... (Review)
Review
Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contributions of genetics and bioactive lipid metabolism in alcohol-induced hepatic lipid accumulation.
Topics: Animals; Ethanol; Humans; Lipid Metabolism; Lipogenesis; Liver
PubMed: 32029510
DOI: 10.1194/jlr.R119000547 -
Endocrine Reviews Oct 2018Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPARα also exhibits... (Review)
Review
Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPARα also exhibits marked anti-inflammatory capacities. The first-generation PPARα agonists, the fibrates, have however been hampered by drug-drug interaction issues, statin drop-in, and ill-designed cardiovascular intervention trials. Notwithstanding, understanding the molecular mechanisms by which PPARα works will enable control of its activities as a drug target for metabolic diseases with an underlying inflammatory component. Given its role in reshaping the immune system, the full potential of this nuclear receptor subtype as a versatile drug target with high plasticity becomes increasingly clear, and a novel generation of agonists may pave the way for novel fields of applications.
Topics: Animals; Humans; Inflammation; Lipid Metabolism; Liver; PPAR alpha
PubMed: 30020428
DOI: 10.1210/er.2018-00064 -
Cell Metabolism Mar 2012Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of... (Review)
Review
Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. New findings that lipolytic products and intermediates participate in cellular signaling processes and that "lipolytic signaling" is particularly important in many nonadipose tissues unveil a previously underappreciated aspect of lipolysis, which may be relevant for human disease.
Topics: Animals; Humans; Lipase; Lipid Metabolism; Lipolysis; Signal Transduction
PubMed: 22405066
DOI: 10.1016/j.cmet.2011.12.018 -
Nature Reviews. Endocrinology Aug 2023Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances... (Review)
Review
Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances uncovering the intricacies of their biogenesis and the diversity of their physiological and pathological roles have yielded new insights into lipid droplet biology. Despite these insights, the mechanisms governing the biogenesis and functions of lipid droplets remain incompletely understood. Moreover, the causal relationship between the biogenesis and function of lipid droplets and human diseases is poorly resolved. Here, we provide an update on the current understanding of the biogenesis and functions of lipid droplets in health and disease, highlighting a key role for lipid droplet biogenesis in alleviating cellular stresses. We also discuss therapeutic strategies of targeting lipid droplet biogenesis, growth or degradation that could be applied in the future to common diseases, such as cancer, hepatic steatosis and viral infection.
Topics: Humans; Lipid Droplets; Lipid Metabolism; Lipogenesis
PubMed: 37221402
DOI: 10.1038/s41574-023-00845-0