scholarly journals Gene cascade analysis in human granulosa tumor cells (KGN) following exposure to high levels of free fatty acids and insulin

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Patricia G. Tremblay ◽  
Chloé Fortin ◽  
Marc-André Sirard
Keyword(s):  
Fatty Acids ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Free Fatty Acids ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Granulosa Cell ◽  
Follicular Fluid ◽  
Obesity And Diabetes ◽  
High Concentrations

AbstractMaternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid and stearic acid reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of palmitic acid, oleic acid, and stearic acid at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.

scholarly journals Concentration-dependent change in hypothalamic neuronal transcriptome by the dietary fatty acids: oleic and palmitic acids

2021 ◽  
Author(s):  
Fabiola Pacheco Valencia ◽  
Amanda F Marino ◽  
Christos Noutsos ◽  
Kinning Poon
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Palmitic Acid ◽  
Signaling Pathways ◽  
High Fat Diet ◽  
High Fat ◽  
High Concentrations ◽  
And Migration ◽  
Palmitic Acids ◽  
Proliferation And Migration

Prenatal high-fat diet exposure increases hypothalamic neurogenesis events in embryos and programs offspring to be obesity-prone. The molecular mechanism involved in these dietary effects of neurogenesis are unknown. This study investigated the effects of oleic and palmitic acids, which are abundant in a high-fat diet, on the hypothalamic neuronal transcriptome and how these changes impact neurogenesis events. The results show differential effects of low and high concentrations of oleic or palmitic acid treatment on differential gene transcription. Gene ontology analysis uncovered significant gene enrichment in several cellular pathways involved in gene regulation and protein production, particularly with proliferation, migration, and cell survival. The enriched signaling pathways include Wnt, integrin, PDGF, and apoptosis, in addition endocrine function signaling pathways CCKR and GnRH. Further examination of proliferation and migration show low concentrations of oleic acid to stimulate proliferation and high concentrations of both oleic and palmitic acid to stimulate apoptosis. Oleic acid also reduced hypothalamic neuronal migration, with little effects by palmitic acid. The results show direct impact of the two most abundant fatty acids in a high fat diet to directly impact hypothalamic neuronal proliferation and migration. The results also uncovered signaling pathways affected by oleic and palmitic acid and suggest a mechanism of prenatal high-fat diet induced neurogenesis events is through these two abundant fatty acids.

scholarly journals The regulation of glyceride synthesis in isolated white-fat cells. The effects of palmitate and lipolytic agents

1972 ◽  
Vol 128 (5) ◽  
pp. 1057-1067 ◽  
Author(s):  
E. D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fat Cells ◽  
Glyceride Synthesis ◽  
Glucose Incorporation ◽  
High Concentrations ◽  
Stimulation Of

1. 0.5mm-Palmitate stimulated incorporation of [U-14C]glucose into glyceride glycerol and fatty acids in normal fat cells in a manner dependent upon the glucose concentration. 2. In the presence of insulin the incorporation of 5mm-glucose into glyceride fatty acids was increased by concentrations of palmitate, adrenaline and 6-N-2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate up to 0.5mm, 0.5μm and 0.5mm respectively. Higher concentrations of these agents produced progressive decreases in the rate of glucose incorporation into fatty acids. 3. The effects of palmitate and lipolytic agents upon the measured parameters of glucose utilization were similar, suggesting that the effects of lipolytic agents are mediated through increased concentrations of free fatty acids. 4. In fat cells from 24h-starved rats, maximal stimulation of glucose incorporation into fatty acids was achieved with 0.25mm-palmitate. Higher concentrations of palmitate were inhibitory. In fat cells from 72h-starved rats, palmitate only stimulated glucose incorporation into fatty acids at high concentrations of palmitate (1mm and above). 5. The ability of fat cells to incorporate glucose into glyceride glycerol in the presence of palmitate decreased with increasing periods of starvation. 6. It is suggested that low concentrations of free fatty acids stimulate fatty acid synthesis from glucose by increasing the utilization of ATP and cytoplasmic NADH for esterification of these free fatty acids. When esterification of free fatty acids does not keep pace with their provision, inhibition of fatty acid synthesis occurs. Provision of free fatty acids far in excess of the esterification capacity of the cells leads to uncoupling of oxidative phosphorylation and a secondary stimulation of fatty acid synthesis from glucose.

Regulation of lysophosphatidylcholine-metabolizing enzymes in isolated myocardial cells from rat heart

1985 ◽  
Vol 63 (8) ◽  
pp. 944-951 ◽  
Author(s):  
David L. Severson ◽  
Thea Fletcher
Keyword(s):  
Fatty Acids ◽  
Palmitic Acid ◽  
Free Fatty Acids ◽  
Rat Heart ◽  
Marked Reduction ◽  
Myocardial Cells ◽  
Acyltransferase Activity ◽  
Metabolizing Enzymes ◽  
Enzymatic Pathways ◽  
Lysophospholipase Activity

Enzymatic pathways involved in the metabolism of lysophosphatidylcholine were investigated in rat heart myocardial cells. Acyl CoA-dependent acyltransferase activity was localized in microsomes, and was much greater than lysophospholipase activity in either cytosolic or microsomal fractions. The cytosolic lysophospholipase was more sensitive to inhibition by palmitylcarnitine in comparison to free fatty acids. In contrast, free fatty acids (oleate and palmitate) produced a greater inhibition of the microsomal acyltransferase and lysophospholipase than did palmitylcarnitine. A reduction in the assay pH to 6.5 resulted in an increase in microsomal acyltransferase and cytosolic lysophospholipase activities, but brought about a marked reduction in the microsomal lysophospholipase activity. At pH 6.5, the percentage inhibition of the microsomal acyltransferase by palmitylcarnitine was reduced, whereas the inhibition by palmitic acid was enhanced. The inhibition of the microsomal lysophospholipase by both palmitylcarnitine and palmitic acid was reduced at pH 6.5. With respect to myocardial ischemia, the inhibition of microsomal acyltransferase by free fatty acids and the reduction in microsomal lysophospholipase activity due to acidosis may contribute to the elevation of cellular lysophosphoglycerides which are arrhythmogenic.

scholarly journals Fatty acid chemistry of Atrichum undulatum and Hypnum andoi

2012 ◽  
Vol 66 (2) ◽  
pp. 207-209 ◽  
Author(s):  
Boris Pejin ◽  
Ljubodrag Vujisic ◽  
Marko Sabovljevic ◽  
Vele Tesevic ◽  
Vlatka Vajs
Keyword(s):  
Fatty Acids ◽  
Gas Chromatography ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Linolenic Acid ◽  
Essential Fatty Acids ◽  
Behenic Acid ◽  
Moss Species

The fatty acid composition of the moss species Atrichum undulatum (Hedw.) P. Beauv. (Polytrichaceae) and Hypnum andoi A.J.E. Sm. (Hypnaceae) collected in winter time were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) as a contribution to their chemistry. Eight fatty acids were identified in the chloroform/methanol extract 1:1 of A. undulatum (linoleic acid 26.80%, palmitic acid 22.17%, ?-linolenic acid 20.50%, oleic acid 18.49%, arachidonic acid 6.21%, stearic acid 3.34%, cis-5,8,11,14,17-eicosapentaenoic acid 1.52% and behenic acid 1.01%), while six fatty acids were found in the same type of extract of H. andoi (palmitic acid 63.48%, erucic acid 12.38%, stearic acid 8.08%, behenic acid 6.26%, lignoceric acid 5.16% and arachidic acid 4.64%). According to this study, the moss A. undulatum can be considered as a good source of both essential fatty acids for humans (linoleic acid and ?-linolenic acid) during the winter.

scholarly journals Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Are Associated With Diet, BMI, and Age

2021 ◽  
Vol 8 ◽  
Author(s):  
Teresa Kellerer ◽  
Karin Kleigrewe ◽  
Beate Brandl ◽  
Thomas Hofmann ◽  
Hans Hauner ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Weight Loss ◽  
Fatty Acid ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Fatty Acid Esters ◽  
Obese Patients ◽  
Hydroxy Stearic Acid ◽  
Diabetic Status ◽  
Acid Esters

Background: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a group of fatty acids with potential anti-inflammatory and anti-diabetic effects. The blood levels of FAHFAs and their regulation in humans have hardly been studied.Objective: We aimed to investigate serum FAHFA levels in well-characterized human cohorts, to evaluate associations with age, sex, BMI, weight loss, diabetic status, and diet.Methods: We analyzed levels of stearic-acid-9-hydroxy-stearic-acid (9-SAHSA), oleic-acid-9-hydroxy-stearic-acid (9-OAHSA) and palmitic-acid-9-hydroxy-palmitic-acid (9-PAHPA) as well as different palmitic acid-hydroxy-stearic-acids (PAHSAs) by HPLC-MS/MS with the use of an internal standard in various cohorts: A cohort of different age groups (18–25y; 40–65y; 75–85y; Σn = 60); severely obese patients undergoing bariatric surgery and non-obese controls (Σn = 36); obese patients with and without diabetes (Σn = 20); vegetarians/vegans (n = 10) and omnivores (n = 9); and young men before and after acute overfeeding with saturated fatty acids (SFA) (n = 15).Results: Omnivores had substantially higher FAHFA levels than vegetarians/vegans [median (25th percentile; 75th percentile) tFAHFAs = 12.82 (7.57; 14.86) vs. 5.86 (5.10; 6.71) nmol/L; P < 0.05]. Dietary overfeeding by supplementation of SFAs caused a significant increase within 1 week [median tFAHFAs = 4.31 (3.31; 5.27) vs. 6.96 (6.50; 7.76) nmol/L; P < 0.001]. Moreover, obese patients had lower FAHFA levels than non-obese controls [median tFAHFAs = 3.24 (2.80; 4.30) vs. 5.22 (4.18; 7.46) nmol/L; P < 0.01] and surgery-induced weight loss increased 9-OAHSA level while other FAHFAs were not affected. Furthermore, significant differences in some FAHFA levels were found between adolescents and adults or elderly, while no differences between sexes and between diabetic and non-diabetic individuals were detected.Conclusions: FAHFA serum levels are strongly affected by high SFA intake and reduced in severe obesity. Age also may influence FAHFA levels, whereas there was no detectable relation with sex and diabetic status. The physiological role of FAHFAs in humans remains to be better elucidated.Trial Registration: All studies referring to these analyses were registered in the German Clinical Trial Register (https://www.drks.de/drks_web/) with the numbers DRKS00009008, DRKS00010133, DRKS00006211, and DRKS00009797.

scholarly journals Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women

1999 ◽  
Vol 81 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Amanda E. Jones ◽  
Michael Stolinski ◽  
Ruth D. Smith ◽  
Jane L. Murphy ◽  
Stephen A. Wootton
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Chain Length ◽  
Time Course ◽  
Absorbed Dose ◽  
Dietary Fatty Acids ◽  
Fatty Acid Chain ◽  
Degree Of Unsaturation

The gastrointestinal handling and metabolic disposal of [1-13C]palmitic acid, [1-13C]stearic acid and [1-13C]oleic acid administered within a lipid–casein–glucose–sucrose emulsion were examined in normal healthy women by determining both the amount and nature of the13C label in stool and label excreted on breath as13CO2. The greatest excretion of13C label in stool was in the stearic acid trial (9.2 % of administered dose) whilst comparatively little label was observed in stool in either the palmitic acid (1.2 % of administered dose) or oleic acid (1.9 % of administered dose) trials. In both the palmitic acid and oleic acid trials, all of the label in stool was identified as being present in the form in which it was administered (i.e. [13C]palmitic acid in the palmitic acid trial and [13C]oleic acid in the oleic acid trial). In contrast, only 87 % of the label in the stool in the stearic acid trial was identified as [13C]stearic acid, the remainder was identified as [13C]palmitic acid which may reflect chain shortening of [1-13C]stearic acid within the gastrointestinal tract. Small, but statistically significant, differences were observed in the time course of recovery of13C label on breath over the initial 9 h of the study period (oleic acid = palmitic acid > stearic acid). However, when calculated over the 24 h study period, the recovery of the label as13CO2was similar in all three trials (approximately 25 % of absorbed dose). These results support the view that chain length and degree of unsaturation may influence the gastrointestinal handling and immediate metabolic disposal of these fatty acids even when presented within an emulsion.

scholarly journals High rates of [1-14C]acetate incorporation into the lipid of isolated spinach chloroplasts

1976 ◽  
Vol 158 (3) ◽  
pp. 593-601 ◽  
Author(s):  
P G Roughan ◽  
C R Slack ◽  
R Holland
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Free Fatty Acids ◽  
Acid Synthesis ◽  
Polar Lipids ◽  
Acetate Incorporation ◽  
Spinach Chloroplasts ◽  
Triton X

Spinach chloroplasts, isolated by techniques yielding preparations with high O2- evolving activity, showed rates of light-dependent acetate incorporation into lipids 3-4 fold higher than any previously reported. Incorporation rates as high as 500 nmol of acetate/h per mg of chlorophyll were measured in buffered sorbitol solutions containing only NaHCO3 and [1-14C]acetate, and as high as 800 nmol/h per mg of chlorophyll when 0.13 mM-Triton X-100 was also included in the reaction media. The fatty acids synthesized were predominantly oleic (70-80% of the total fatty acid radioactivity) and palmitic (20-25%) with only minor amounts (1-5%) of linoleic acid. Linolenic acid synthesis was not detected in the system in vitro. Free fatty acids accounted for 70-90% of the radioactivity incorporated and the remainder was shared fairly evenly between 1,2-diacylglycerols and polar lipids. Oleic acid constituted 80-90% of the free fatty acids synthesized, but the diacylglycerols and polar lipids contained slightly more palmitic acid than oleic acid. Triton X-100 stimulated the synthesis of diacylglycerols 3-6 fold, but stimulated free fatty acid synthesis only 1-1.5-fold. Added glycerol 1-phosphate stimulated both the synthesis of diacylglycerols and palmitic acid relative to oleic acid, but did not increase acetate incorporation into total chloroplast lipids. CoA and ATP, when added separately, stimulated acetate incorporation into chloroplast lipids to variable extents and had no effect on the types of lipid synthesized, but when added together resulted in 34% of the incorporated acetate appearing in long-chain acyl-CoA. Pyruvate was a much less effective precursor of chloroplast fatty acids than was acetate.

scholarly journals Minimizing Contamination from Plastic Labware in the Quantification of C16 and C18 Fatty Acids in Filter Samples of Atmospheric Particulate Matter and Their Utility in Apportioning Cooking Source Contribution to Urban PM2.5

Atmosphere ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1120
Author(s):  
Yuk Ying Cheng ◽  
Jian Zhen Yu
Keyword(s):  
Fatty Acids ◽  
Hong Kong ◽  
Particulate Matter ◽  
Fatty Acid ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
New Method ◽  
Urban Site ◽  
Plastic Syringe ◽  
Syringe Filter

Palmitic acid (C16:0) and stearic acid (C18:0) are among the most abundant products in cooking emission, and thus could serve as potential molecular tracers in estimating the contributions of cooking emission to particulate matter (PM2.5) pollution in the atmosphere. Organic tracer analysis in filter-based samples generally involves extraction by organic solvents, followed by filtration. In these procedures, disposable plastic labware is commonly used due to convenience and as a precaution against sample-to-sample cross contamination. However, we observed contamination for both C16:0 and C18:0 fatty acids, their levels reaching 6–8 ppm in method blanks and leading to their detection in 9% and 42% of PM2.5 samples from Hong Kong, indistinguishable from the blank. We present in this work the identification of plastic syringe and plastic syringe filter disc as the contamination sources. We further demonstrated that a new method procedure using glass syringe and stainless-steel syringe filter holder offers a successful solution. The new method has reduced the contamination level from 6.6 ± 1.2 to 2.6 ± 0.9 ppm for C16:0 and from 8.9 ± 2.1 to 1.9 ± 0.8 ppm for C18:0 fatty acid. Consequently, the limit of detection (LOD) for C16:0 has decreased by 57% from 1.8 to 0.8 ppm and 56% for C18:0 fatty acid from 3.2 to 1.4 ppm. Reductions in both LOD and blank variability has allowed the increase in quantification rate of the two fatty acids in ambient samples and thereby retrieving more data for estimating the contribution of cooking emission to ambient PM2.5. With the assistance of three cooking related tracers, palmitic acid (C16:0), stearic acid (C18:0) and cholesterol, positive matrix factorization analysis of a dataset of PM2.5 samples collected from urban Hong Kong resolved a cooking emission source. The results indicate that cooking was a significant local PM2.5 source, contributing to an average of 2.2 µgC/m3 (19%) to organic carbon at a busy downtown roadside location and 1.8 µgC/m3 (15%) at a general urban site.

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