Potential Mechanisms Underlying the Role of Coffee in Liver Health

AbstractCoffee, the most consumed hot beverage worldwide, is composed of many substances, of which polyphenols, caffeine, and diterpenoids are well studied. Evidence on potential effects of coffee on human health has been accumulating over the past decades. Specifically, coffee has been postulated to be hepatoprotective in several epidemiological and clinical studies. Several underlying molecular mechanisms as to why coffee influences liver health have been proposed. In this review, the authors summarized the evidence on potential mechanisms by which coffee affects liver steatosis, fibrosis, and hepatic carcinogenesis. The experimental models reviewed almost unanimously supported the theorem that coffee indeed may benefit the liver. Either whole coffee or its specific compounds appeared to decrease fatty acid synthesis (involved in steatogenesis), hepatic stellate activation (involved in fibrogenesis), and hepatic inflammation. Moreover, coffee was found to induce apoptosis and increased hepatic antioxidant capacity, which are involved in carcinogenesis.

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Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.010233 ◽

2019 ◽

Vol 295 (4) ◽

pp. 994-1008 ◽

Cited By ~ 2

Author(s):

Nancy Magee ◽

An Zou ◽

Priyanka Ghosh ◽

Forkan Ahamed ◽

Don Delker ◽

...

Keyword(s):

Nonalcoholic Steatohepatitis ◽

Molecular Mechanisms ◽

Liver Steatosis ◽

Chow Diet ◽

Peroxisome Proliferator ◽

Rna Seq ◽

Hepatic Inflammation ◽

Peroxisome Proliferator Activated Receptor ◽

Small Heterodimer Partner

Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide and is characterized by steatosis, inflammation, and fibrosis. The molecular mechanisms underlying NASH development remain obscure. The nuclear receptor small heterodimer partner (Shp) plays a complex role in lipid metabolism and inflammation. Here, we sought to determine SHP's role in regulating steatosis and inflammation in NASH. Shp deletion in murine hepatocytes (ShpHep−/−) resulted in massive infiltration of macrophages and CD4+ T cells in the liver. ShpHep−/− mice developed reduced steatosis, but surprisingly increased hepatic inflammation and fibrosis after being fed a high-fat, -cholesterol, and -fructose (HFCF) diet. RNA-Seq analysis revealed that pathways involved in inflammation and fibrosis are significantly activated in the liver of ShpHep−/− mice fed a chow diet. After having been fed the HFCF diet, WT mice displayed up-regulated peroxisome proliferator-activated receptor γ (Pparg) signaling in the liver; however, this response was completely abolished in the ShpHep−/− mice. In contrast, livers of ShpHep−/− mice had consistent NF-κB activation. To further characterize the role of Shp specifically in the transition of steatosis to NASH, mice were fed the HFCF diet for 4 weeks, followed by Shp deletion. Surprisingly, Shp deletion after steatosis development exacerbated hepatic inflammation and fibrosis without affecting liver steatosis. Together, our results indicate that, depending on NASH stage, hepatic Shp plays an opposing role in steatosis and inflammation. Mechanistically, Shp deletion in hepatocytes activated NF-κB and impaired Pparg activation, leading to the dissociation of steatosis, inflammation, and fibrosis in NASH development.

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Genome-Wide Mapping of Histone H3 Lysine 4 Trimethylation (H3K4me3) and Its Involvement in Fatty Acid Biosynthesis in Sunflower Developing Seeds

Plants ◽

10.3390/plants10040706 ◽

2021 ◽

Vol 10 (4) ◽

pp. 706

Author(s):

Antonio J. Moreno-Pérez ◽

Raquel Martins-Noguerol ◽

Cristina DeAndrés-Gil ◽

Mónica Venegas-Calerón ◽

Rosario Sánchez ◽

...

Keyword(s):

Fatty Acid ◽

Chromatin Remodeling ◽

Molecular Mechanisms ◽

Acid Metabolism ◽

Fatty Acid Biosynthesis ◽

Acid Synthesis ◽

Sunflower Seeds ◽

Acid Biosynthesis ◽

Functional Regions ◽

Genome Wide

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.

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FSMP-15. EVALUATING THE ROLE OF LONG-CHAIN FATTY ACID METABOLISM IN PROMOTING GLIOBLASTOMA GROWTH

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab024.079 ◽

2021 ◽

Vol 3 (Supplement_1) ◽

pp. i19-i19

Author(s):

Divya Ravi ◽

Carmen del Genio ◽

Haider Ghiasuddin ◽

Arti Gaur

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Survival Rate ◽

Tumor Progression ◽

Acid Synthesis ◽

Normal Brain ◽

Acid Uptake ◽

Exogenous Fatty Acid ◽

Long Chain

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.

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The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

BioMed Research International ◽

10.1155/2014/318030 ◽

2014 ◽

Vol 2014 ◽

pp. 1-19 ◽

Cited By ~ 26

Author(s):

Norahayu Othman ◽

Noor Hasima Nagoor

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

High Frequency ◽

Tumor Suppressor Genes ◽

Molecular Mechanisms ◽

Lung Carcinogenesis ◽

The Past ◽

Late Stage Diagnosis ◽

Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

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The Role of Succinate in the Regulation of Fatty Acid Synthesis by Heart Mitochondria

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)95771-6 ◽

1967 ◽

Vol 242 (18) ◽

pp. 4013-4022 ◽

Cited By ~ 1

Author(s):

Arthur F. Whereat ◽

Franklin E. Hull ◽

Margaret W. Orishimo ◽

Joseph L. Rabinowitz

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Heart Mitochondria

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The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Cancers ◽

10.3390/cancers13184576 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4576

Author(s):

Hung-Yu Lin ◽

Hui-Wen Ho ◽

Yen-Hsiang Chang ◽

Chun-Jui Wei ◽

Pei-Yi Chu

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Drug Resistant ◽

Therapeutic Targeting ◽

The Past ◽

Regulated Cell Death ◽

Common Malignancy

Breast cancer (BC) is the most common malignancy among women worldwide. The discovery of regulated cell death processes has enabled advances in the treatment of BC. In the past decade, ferroptosis, a new form of iron-dependent regulated cell death caused by excessive lipid peroxidation has been implicated in the development and therapeutic responses of BC. Intriguingly, the induction of ferroptosis acts to suppress conventional therapy-resistant cells, and to potentiate the effects of immunotherapy. As such, pharmacological or genetic modulation targeting ferroptosis holds great potential for the treatment of drug-resistant cancers. In this review, we present a critical analysis of the current understanding of the molecular mechanisms and regulatory networks involved in ferroptosis, the potential physiological functions of ferroptosis in tumor suppression, its potential in therapeutic targeting, and explore recent advances in the development of therapeutic strategies for BC.

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The role of pyruvate hub enzymes in supplying carbon precursors for fatty acid synthesis in photosynthetic microalgae

Photosynthesis Research ◽

10.1007/s11120-015-0136-7 ◽

2015 ◽

Vol 125 (3) ◽

pp. 407-422 ◽

Cited By ~ 28

Author(s):

Nastassia Shtaida ◽

Inna Khozin-Goldberg ◽

Sammy Boussiba

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthesis ◽

Acid Synthesis

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Mitochondrial Dysfunction in Obesity and Reproduction

Endocrinology ◽

10.1210/endocr/bqaa158 ◽

2020 ◽

Vol 162 (1) ◽

Author(s):

Manasi Das ◽

Consuelo Sauceda ◽

Nicholas J G Webster

Keyword(s):

Mitochondrial Dysfunction ◽

Energy Production ◽

Molecular Mechanisms ◽

Human Populations ◽

Metabolic Alterations ◽

Genetic Manipulations ◽

The Past ◽

Calcium Buffering

Abstract Mounting evidence suggests a role for mitochondrial dysfunction in the pathogenesis of many diseases, including type 2 diabetes, aging, and ovarian failure. Because of the central role of mitochondria in energy production, heme biosynthesis, calcium buffering, steroidogenesis, and apoptosis signaling within cells, understanding the molecular mechanisms behind mitochondrial dysregulation and its potential implications in disease is critical. This review will take a journey through the past and summarize what is known about mitochondrial dysfunction in various disorders, focusing on metabolic alterations and reproductive abnormalities. Evidence is presented from studies in different human populations, and rodents with genetic manipulations of pathways known to affect mitochondrial function.

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The Role of Vitamin D and the Vitamin D Receptor in Bone Oncology

Osteologie/Osteology ◽

10.1055/s-0038-1673534 ◽

2018 ◽

Vol 27 (03) ◽

pp. 129-134 ◽

Cited By ~ 1

Author(s):

B. M. Holzapfel ◽

F. Jakob ◽

A. A. Kurth ◽

G. Maier ◽

K. Horas

Keyword(s):

Vitamin D ◽

Cancer Cells ◽

Vitamin D Deficiency ◽

Vitamin D Receptor ◽

Molecular Mechanisms ◽

Full Range ◽

Cancer Cell Growth ◽

The Past ◽

Global Health Problem

SummaryVitamin D deficiency is a global health problem of enormous and increasing dimensions. In the past decades, numerous studies have centered on the role of vitamin D in the pathogenesis and course of many diseases including several types of cancer. Indeed, vitamin D has been widely acknowledged to be involved in the regulation of cell proliferation, differentiation and apoptosis in numerous cancer cells. While the full range of molecular mechanisms involveld in cancer cell growth and progression remains to be elucidated, recent research has deepened our understanding of the processes that may be affected by vitamin D or vitamin D deficiency.In this review, we consider the properties of bone that enable cancer cells to grow and thrive within the skeleton, and the role of vitamin D and the vitamin D receptor in the process of primary and secondary cancer growth in bone.

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