Role of endogenous fatty acids in the control of hepatic gluconeogenesis

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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Role of saturated and unsaturated fatty acids on dicarbonyl–albumin derived advanced glycation end products in vitro

Amino Acids ◽

10.1007/s00726-021-03069-6 ◽

2021 ◽

Author(s):

Brock Peake ◽

Maulik Ghetia ◽

Cobus Gerber ◽

Maurizio Costabile ◽

Permal Deo

Keyword(s):

Fatty Acids ◽

Advanced Glycation End Products ◽

Unsaturated Fatty Acids ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products

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Evaluation of Chemical Variability of Cured Vanilla Beans (Vanilla tahitensis and Vanilla planifolia)

Natural Product Communications ◽

10.1177/1934578x0900401016 ◽

2009 ◽

Vol 4 (10) ◽

pp. 1934578X0900401 ◽

Cited By ~ 1

Author(s):

Christel Brunschwig ◽

François Xavier Collard ◽

Jean-Pierre Bianchini ◽

Phila Raharivelomanana

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Dry Matter ◽

Monounsaturated Fatty Acids ◽

Vanilla Planifolia ◽

Chemical Variability ◽

Total Fatty Acids ◽

Curing Method ◽

Fatty Acid Compositions

In order to establish a chemical fingerprint of vanilla diversity, thirty samples of V. planifolia J. W. Moore and V. tahitensis G. Jackson cured beans from seven producing countries were examined for their aroma and fatty acid contents. Both fatty acid and aroma compositions were found to vary between vanilla species and origins. Vanillin was found in higher amounts in V. planifolia (1.7-3.6% of dry matter) than in V. tahitensis (1.0-2.0%), and anisyl compounds were found in lower amounts in V. planifolia (0.05%) than in V. tahitensis (1.4%-2.1%). Ten common and long chain monounsaturated fatty acids (LCFA) were identified and were found to be characteristic of the vanilla origin. LCFA derived from secondary metabolites have discriminating compositions as they reach 5.9% and 15.8% of total fatty acids, respectively in V. tahitensis and V. planifolia. This study highlights the role of the curing method as vanilla cured beans of two different species cultivated in the same country were found to have quite similar fatty acid compositions.

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The Properties and Role of O-Acyl-ω-hydroxy Fatty Acids and Type I-St and Type II Diesters in the Tear Film Lipid Layer Revealed by a Combined Chemistry and Biophysics Approach

The Journal of Organic Chemistry ◽

10.1021/acs.joc.0c02882 ◽

2021 ◽

Author(s):

Tuomo Viitaja ◽

Jan-Erik Raitanen ◽

Jukka Moilanen ◽

Riku O. Paananen ◽

Filip S. Ekholm

Keyword(s):

Fatty Acids ◽

Tear Film ◽

Hydroxy Fatty Acids ◽

Type I ◽

Type Ii ◽

Lipid Layer

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The Effect of Fusarium verticillioides Fumonisins on Fatty Acids, Sphingolipids, and Oxylipins in Maize Germlings

International Journal of Molecular Sciences ◽

10.3390/ijms22052435 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2435

Author(s):

Marzia Beccaccioli ◽

Manuel Salustri ◽

Valeria Scala ◽

Matteo Ludovici ◽

Andrea Cacciotti ◽

...

Keyword(s):

Fatty Acids ◽

Fusarium Verticillioides ◽

Fungal Growth ◽

Defense Responses ◽

Ceramide Synthase ◽

Ear Rot ◽

In Planta ◽

Disease Symptoms ◽

The Impact

Fusarium verticillioides causes multiple diseases of Zea mays (maize) including ear and seedling rots, contaminates seeds and seed products worldwide with toxic chemicals called fumonisins. The role of fumonisins in disease is unclear because, although they are not required for ear rot, they are required for seedling diseases. Disease symptoms may be due to the ability of fumonisins to inhibit ceramide synthase activity, the expected cause of lipids (fatty acids, oxylipins, and sphingolipids) alteration in infected plants. In this study, we explored the impact of fumonisins on fatty acid, oxylipin, and sphingolipid levels in planta and how these changes affect F. verticillioides growth in maize. The identity and levels of principal fatty acids, oxylipins, and over 50 sphingolipids were evaluated by chromatography followed by mass spectrometry in maize infected with an F. verticillioides fumonisin-producing wild-type strain and a fumonisin-deficient mutant, after different periods of growth. Plant hormones associated with defense responses, i.e., salicylic and jasmonic acid, were also evaluated. We suggest that fumonisins produced by F. verticillioides alter maize lipid metabolism, which help switch fungal growth from a relatively harmless endophyte to a destructive necrotroph.

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TCA Cycle and Fatty Acids Oxidation Reflect Early Cardiorenal Damage in Normoalbuminuric Subjects with Controlled Hypertension

Antioxidants ◽

10.3390/antiox10071100 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1100

Author(s):

Aranzazu Santiago-Hernandez ◽

Marta Martin-Lorenzo ◽

Ariadna Martin-Blazquez ◽

Gema Ruiz-Hurtado ◽

Maria G Barderas ◽

...

Keyword(s):

Fatty Acids ◽

Tricarboxylic Acid Cycle ◽

Renin Angiotensin System ◽

Roc Curves ◽

Tca Cycle ◽

Urinary Metabolites ◽

Organ Damage ◽

Fatty Acid Binding ◽

Angiotensin System

Moderately increased albuminuria, defined by an albumin to creatinine ratio (ACR) > 30 mg/g, is an indicator of subclinical organ damage associated with a higher risk of cardiovascular and renal disease. Normoalbuminuric subjects are considered at no cardiorenal risk in clinical practice, and molecular changes underlying early development are unclear. To decipher subjacent mechanisms, we stratified the normoalbuminuria condition. A total of 37 hypertensive patients under chronic renin–angiotensin system (RAS) suppression with ACR values in the normoalbuminuria range were included and classified as control (C) (ACR < 10 mg/g) and high-normal (HN) (ACR = 10–30 mg/g). Target metabolomic analysis was carried out by liquid chromatography and mass spectrometry to investigate the role of the cardiorenal risk urinary metabolites previously identified. Besides this, urinary free fatty acids (FFAs), fatty acid binding protein 1 (FABP1) and nephrin were analyzed by colorimetric and ELISA assays. A Mann–Whitney test was applied, ROC curves were calculated and Spearman correlation analysis was carried out. Nine metabolites showed significantly altered abundance in HN versus C, and urinary FFAs and FABP1 increased in HN group, pointing to dysregulation in the tricarboxylic acid cycle (TCA) cycle and fatty acids β-oxidation. We showed here how cardiorenal metabolites associate with albuminuria, already in the normoalbuminuric range, evidencing early renal damage at a tubular level and suggesting increased β-oxidation to potentially counteract fatty acids overload in the HN range.

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Dissecting the Roles of Cuticular Wax in Plant Resistance to Shoot Dehydration and Low-Temperature Stress in Arabidopsis

International Journal of Molecular Sciences ◽

10.3390/ijms22041554 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1554

Author(s):

Tawhidur Rahman ◽

Mingxuan Shao ◽

Shankar Pahari ◽

Prakash Venglat ◽

Raju Soolanayakanahally ◽

...

Keyword(s):

Fatty Acids ◽

Low Temperature ◽

Cold Acclimation ◽

Water Loss ◽

Cuticular Wax ◽

Dehydration Stress ◽

Wax Deposition ◽

Cuticular Waxes ◽

Gas Chromatography Mass Spectroscopy

Cuticular waxes are a mixture of hydrophobic very-long-chain fatty acids and their derivatives accumulated in the plant cuticle. Most studies define the role of cuticular wax largely based on reducing nonstomatal water loss. The present study investigated the role of cuticular wax in reducing both low-temperature and dehydration stress in plants using Arabidopsis thaliana mutants and transgenic genotypes altered in the formation of cuticular wax. cer3-6, a known Arabidopsis wax-deficient mutant (with distinct reduction in aldehydes, n-alkanes, secondary n-alcohols, and ketones compared to wild type (WT)), was most sensitive to water loss, while dewax, a known wax overproducer (greater alkanes and ketones compared to WT), was more resistant to dehydration compared to WT. Furthermore, cold-acclimated cer3-6 froze at warmer temperatures, while cold-acclimated dewax displayed freezing exotherms at colder temperatures compared to WT. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis identified a characteristic decrease in the accumulation of certain waxes (e.g., alkanes, alcohols) in Arabidopsis cuticles under cold acclimation, which was additionally reduced in cer3-6. Conversely, the dewax mutant showed a greater ability to accumulate waxes under cold acclimation. Fourier Transform Infrared Spectroscopy (FTIR) also supported observations in cuticular wax deposition under cold acclimation. Our data indicate cuticular alkane waxes along with alcohols and fatty acids can facilitate avoidance of both ice formation and leaf water loss under dehydration stress and are promising genetic targets of interest.

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