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The New England Journal of Medicine Jun 1953
Topics: Fats; Lipid Metabolism; Lipogenesis
PubMed: 13046655
DOI: 10.1056/NEJM195306042482302 -
Nutrients Sep 2019Recent evidences have linked indole-3-acetic acid (IAA), a gut microbiota-derived metabolite from dietary tryptophan, with the resistance to liver diseases. However,...
Recent evidences have linked indole-3-acetic acid (IAA), a gut microbiota-derived metabolite from dietary tryptophan, with the resistance to liver diseases. However, data supporting IAA-mediated protection against nonalcoholic fatty liver disease (NAFLD) from an in vivo study is lacking. In this study, we assessed the role of IAA in attenuating high-fat diet (HFD)-induced NAFLD in male C57BL/6 mice. Administration of IAA (50 mg/kg body weight) by intraperitoneal injection was found to alleviate HFD-induced elevation in fasting blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index as well as plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), and glutamic-pyruvic transaminase (GPT) activity. Histological examination further presented the protective effect of IAA on liver damage induced by HFD feeding. HFD-induced an increase in liver total triglycerides and cholesterol, together with the upregulation of genes related to lipogenesis including sterol regulatory element binding-protein 1 (Srebf1), steraroyl coenzyme decarboxylase 1 (Scd1), peroxisome proliferator-activated receptor gamma (PPARγ), acetyl-CoA carboxylase 1 (Acaca), and glycerol-3-phosphate acyltransferase, mitochondrial (Gpam), which were mitigated by IAA treatment. The results of reactive oxygen species (ROS) and malonaldehyde (MDA) level along with superoxide dismutase (SOD) activity and glutathione (GSH) content in liver tissue evidenced the protection of IAA against HFD-induced oxidative stress. Additionally, IAA attenuated the inflammatory response of liver in mice exposed to HFD as shown by the reduction in the F4/80-positive macrophage infiltration and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). In conclusion, our findings uncover that IAA alleviates HFD-induced hepatotoxicity in mice, which proves to be associated with the amelioration in insulin resistance, lipid metabolism, and oxidative and inflammatory stress.
Topics: Animals; Indoleacetic Acids; Inflammation; Lipids; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress
PubMed: 31484323
DOI: 10.3390/nu11092062 -
International Journal of Oncology Aug 2014In normal tissues, energy-providing lipids come principally from circulating lipids. However, in growing tumors, energy supply is mainly provided by lipids coming from... (Review)
Review
In normal tissues, energy-providing lipids come principally from circulating lipids. However, in growing tumors, energy supply is mainly provided by lipids coming from de novo synthesis. It is not surprising to see elevated expression of several lipogenic genes in tumors from different origins. The role of lipogenic genes in the establishment of the primary tumor has been clearly established. A large number of studies demonstrate a role of fatty acid synthase in the activation of cell cycle and inhibition of apoptosis in tumor cells. Other lipogenic genes such as the acetyl CoA carboxylase (ACC) and the stearoyl CoA desaturase 1 (SCD1) are highly expressed in primary tumors and also appear to play a role in their development. However, the role of lipogenesis in the metastatic process is less clear. In the present review, we aim to present the most recent evidences for the key role of lipogenic enzymes in the metastatic process and in epithelial to mesenchymal transition.
Topics: Animals; Disease Progression; Epithelial-Mesenchymal Transition; Humans; Lipogenesis; Neoplasms; Signal Transduction
PubMed: 24827738
DOI: 10.3892/ijo.2014.2441 -
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 -
JCI Insight Mar 2023Cancer stem-like cells (CSCs) are critically involved in cancer metastasis and chemoresistance, acting as one major obstacle in clinical practice. While accumulating...
Cancer stem-like cells (CSCs) are critically involved in cancer metastasis and chemoresistance, acting as one major obstacle in clinical practice. While accumulating studies have implicated the metabolic reprogramming of CSCs, mitochondrial dynamics in such cells remain poorly understood. Here we pinpointed OPA1hi with mitochondrial fusion as a metabolic feature of human lung CSCs, licensing their stem-like properties. Specifically, human lung CSCs exerted enhanced lipogenesis, inducing OPA1 expression via transcription factor SAM Pointed Domain containing ETS transcription Factor (SPDEF). In consequence, OPA1hi promoted mitochondrial fusion and stemness of CSCs. Such lipogenesishi, SPDEFhi, and OPA1hi metabolic adaptions were verified with primary CSCs from lung cancer patients. Accordingly, blocking lipogenesis and mitochondrial fusion efficiently impeded CSC expansion and growth of organoids derived from patients with lung cancer. Together, lipogenesis regulates mitochondrial dynamics via OPA1 for controlling CSCs in human lung cancer.
Topics: Humans; Mitochondrial Dynamics; Lipogenesis; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Transcription Factors
PubMed: 36809297
DOI: 10.1172/jci.insight.158429 -
Seminars in Liver Disease Feb 2022Metabolic rewiring is one of the hallmarks of cancer. Altered de novo lipogenesis is one of the pivotal metabolic events deregulated in cancers. Sterol regulatory...
Metabolic rewiring is one of the hallmarks of cancer. Altered de novo lipogenesis is one of the pivotal metabolic events deregulated in cancers. Sterol regulatory element-binding transcription factor 1 (SREBP1) controls the transcription of major enzymes involved in de novo lipogenesis, including ACLY, ACACA, FASN, and SCD. Studies have shown the increased de novo lipogenesis in human hepatocellular carcinoma (HCC) samples. Multiple mechanisms, such as activation of the AKT/mechanistic target of rapamycin (mTOR) pathway, lead to high SREBP1 induction and the coordinated enhanced expression of , , and genes. Subsequent functional analyses have unraveled these enzymes' critical role(s) and the related de novo lipogenesis in hepatocarcinogenesis. Importantly, targeting these molecules might be a promising strategy for HCC treatment. This paper comprehensively summarizes de novo lipogenesis rewiring in HCC and how this pathway might be therapeutically targeted.
Topics: Carcinogenesis; Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Lipogenesis; Liver Neoplasms
PubMed: 34311471
DOI: 10.1055/s-0041-1731709 -
Diabetes Jul 2016Recent studies have shown that in addition to their traditionally recognized functions as building blocks, energy stores, or hazardous intermediates, lipids also have... (Review)
Review
Recent studies have shown that in addition to their traditionally recognized functions as building blocks, energy stores, or hazardous intermediates, lipids also have the ability to act as signaling molecules with potent effects on systemic metabolism and metabolic diseases. This Perspective highlights this somewhat less apparent biology of lipids, especially focusing on de novo lipogenesis as a process that gives rise to key messenger molecules mediating interorgan communication. Elucidating the mechanisms of lipid-dependent coordination of metabolism promises invaluable insights into the understanding of metabolic diseases and may contribute to the development of a new generation of preventative and therapeutic approaches.
Topics: Adipose Tissue; Animals; Fatty Acids; Lipogenesis; Liver; Signal Transduction
PubMed: 27288005
DOI: 10.2337/db16-0251 -
Biotechnology Advances Nov 2018Since cancer cells depend on de novo lipogenesis for energy supply, highly active membrane biosynthesis and signaling, enhanced fatty acid synthesis is a crucial... (Review)
Review
Since cancer cells depend on de novo lipogenesis for energy supply, highly active membrane biosynthesis and signaling, enhanced fatty acid synthesis is a crucial characteristic of cancer cells. Hence, targeting lipogenic enzymes and signaling cascades is a very promising approach in developing innovative therapeutic agents for the fight against cancer. This review summarizes main aspects of altered fatty acid synthesis in cancer cells and emphasizes the power of chemical genetic approaches in identifying and analyzing novel anti-cancer drug candidates interfering with lipid metabolism.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Humans; Lipogenesis; Mice; Neoplasms; Signal Transduction
PubMed: 29447918
DOI: 10.1016/j.biotechadv.2018.02.007 -
The Journal of Clinical Investigation Jun 2020Hepatic de novo lipogenesis is a major contributor to nonalcoholic fatty liver disease (NAFLD). In this issue of the JCI, Liu and Lin et al. identified Slug as an...
Hepatic de novo lipogenesis is a major contributor to nonalcoholic fatty liver disease (NAFLD). In this issue of the JCI, Liu and Lin et al. identified Slug as an epigenetic regulator of lipogenesis. Their findings suggest that Slug is stabilized by insulin signaling, and that it promotes lipogenesis by recruiting the histone demethylase Lsd1 to the fatty acid synthase gene promoter. On the other hand, genetic deletion or acute depletion of Slug, or Lsd1 inhibition, reduced lipogenesis and protected against obesity-associated NAFLD and insulin resistance in mice. This study advances our understanding of how lipogenesis is regulated downstream of insulin signaling in health and disease.
Topics: Animals; Epigenesis, Genetic; Insulin; Insulin Resistance; Lipogenesis; Liver; Mice; Non-alcoholic Fatty Liver Disease
PubMed: 32364539
DOI: 10.1172/JCI137050 -
International Journal of Biological... Jul 2023Patients with Alzheimer's disease (AD) display both peripheral tissue and brain insulin resistance, the later could be a potential risk factor for cognitive dysfunction.... (Review)
Review
Patients with Alzheimer's disease (AD) display both peripheral tissue and brain insulin resistance, the later could be a potential risk factor for cognitive dysfunction. While certain degree of inflammation is required for inducing insulin resistance, underlying mechanism(s) remains unclear. Evidence from diverse research domains suggest that elevated intracellular fatty acids of de novo pathway can induce insulin resistance even without triggering inflammation; however, the effect of saturated fatty acids (SFAs) could be detrimental due the development of proinflammatory cues. In this context, evidence suggest that while lipid/fatty acid accumulation is a characteristic feature of brain pathology in AD, dysregulated de novo lipogenesis could be a potential source for lipid/fatty acid accumulation. Therefore, therapies aimed at regulating de novo lipogenesis could be effective in improving insulin sensitivity and cognitive function in patients with AD.
Topics: Humans; Insulin Resistance; Lipogenesis; Liver; Alzheimer Disease; Fatty Acids; Inflammation
PubMed: 37187418
DOI: 10.1016/j.ijbiomac.2023.124859