-
Cells Mar 2022Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients and is characterized by unintentional weight loss and tissue wasting. To understand the...
Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients and is characterized by unintentional weight loss and tissue wasting. To understand the metabolic changes that occur in PDAC-associated cachexia, we compared the abundance of plasma fatty acids (FAs), measured by gas chromatography, of subjects with treatment-naïve metastatic PDAC with or without cachexia, defined as a loss of > 2% weight and evidence of sarcopenia (n = 43). The abundance of saturated, monounsaturated, and polyunsaturated FAs was not different between subjects with cachexia and those without. Oleic acid was significantly higher in subjects with cachexia (p = 0.0007) and diabetes (p = 0.015). Lauric (r = 0.592, p = 0.0096) and eicosapentaenoic (r = 0.564, p = 0.015) acids were positively correlated with age in cachexia patients. Subjects with diabetes (p = 0.021) or both diabetes and cachexia (p = 0.092) had low palmitic:oleic acid ratios. Linoleic acid was lower in subjects with diabetes (p = 0.018) and correlated with hemoglobin (r = 0.519, p = 0.033) and albumin (r = 0.577, p = 0.015) in subjects with cachexia. Oleic or linoleic acid may be useful treatment targets or biomarkers of cachexia in patients with metastatic PDAC, particularly those with diabetes.
Topics: Adenocarcinoma; Cachexia; Carcinoma, Pancreatic Ductal; Fatty Acids; Humans; Linoleic Acids; Oleic Acid; Pancreatic Neoplasms
PubMed: 35269531
DOI: 10.3390/cells11050910 -
International Journal of Molecular... Sep 2021The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential...
The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (), fatty acid synthase () and sterol regulatory element binding protein 1c (). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (), and its target genes, carnitine palmitoyl transferase 1 () and acyl-coenzyme A oxidase 1 () in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator's, tumor necrosis factor ()-α, interleukin-6 (), , and secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.
Topics: AMP-Activated Protein Kinases; Animals; Benzopyrans; Cell Line, Tumor; Fatty Acids, Nonesterified; Hepatocytes; Humans; Inflammation; Lipid Metabolism; Lipids; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Oleic Acid; Phyllanthus; Reactive Oxygen Species; Signal Transduction; Triglycerides
PubMed: 34576229
DOI: 10.3390/ijms221810062 -
Journal of Dairy Science Jun 2023Excessive adipose tissue (AT) lipolysis around parturition in dairy cows is associated with impaired AT insulin sensitivity and increased incidence of metabolic...
Excessive adipose tissue (AT) lipolysis around parturition in dairy cows is associated with impaired AT insulin sensitivity and increased incidence of metabolic diseases. Supplementing cows with oleic acid (OA) reduces circulating biomarkers of lipolysis and improves energy balance. Nevertheless, it is unclear if OA alters lipid trafficking in AT. In the liver and skeletal muscle, OA improves mitochondrial function and promotes lipid droplet formation by activating perilipin 5 (PLIN5) and peroxisome proliferator-activated receptor α (PPARα). However, it is unknown if this mechanism occurs in AT. The objective of this study was to determine the effect of OA on AT lipolysis, systemic and AT insulin sensitivity, and AT mitochondrial function in periparturient dairy cows. Twelve rumen-cannulated Holstein cows were infused abomasally following parturition with ethanol (CON) or OA (60 g/d) for 14 d. Subcutaneous AT samples were collected at 11 ± 3.6 d before calving (-12 d), and 6 ± 1.0 d (7 d) and 13 ± 1.4 d (14 d) after parturition. An intravenous glucose tolerance test was performed on d 14. Adipocyte morphometry was performed on hematoxylin and eosin-stained AT sections. The antilipolytic effect of insulin (1 μg/L) was evaluated using an ex vivo explant culture following lipolysis stimulation. PLIN5 and PPARα transcription and translation were determined by real-time quantitative PCR and capillary electrophoresis, respectively. RNA sequencing was used to evaluate the transcriptomic profile of mitochondrial gene networks. In CON cows, postpartum lipolysis increased the percentage of smaller (<3,000 µm) adipocytes at 14 d compared with -12 d. However, OA limited adipocyte size reduction at 14 d. Likewise, OA decreased lipolysis plasma markers nonesterified free fatty acids and β-hydroxybutyrate at 5 and 7 d. Over the 14-d period, compared with CON, OA increased the concentration of plasma insulin and decreased plasma glucose. During the glucose tolerance test, OA decreased circulating glucose concentration (at 10, 20, 30, 40 min) and the glucose clearance rate. Moreover, OA increased insulin at 10 and 20 min and tended to increase it at 30 min. Following lipolysis stimulation, OA improved the antilipolytic effect of insulin in the AT at 14 d. PLIN5 and PPARA gene expression decreased postpartum regardless of treatment. However, OA increased PLIN5 protein expression at 14 d and increased PPARA at 7 and 14 d. Immunohistochemical analysis of AT and RNA sequencing data showed that OA increased the number of mitochondria and improved mitochondrial function. However, OA had no effect on production and digestibility. Our results demonstrate that OA limits AT lipolysis, improves systemic and AT insulin sensitivity, and is associated with markers of mitochondrial function supporting a shift to lipogenesis in AT of periparturient dairy cows.
Topics: Female; Cattle; Animals; Lipolysis; Insulin Resistance; Oleic Acid; PPAR alpha; Lactation; Diet; Adipose Tissue; Glucose; Insulin; Fatty Acids, Nonesterified; Cattle Diseases
PubMed: 37105874
DOI: 10.3168/jds.2022-22402 -
Molecules (Basel, Switzerland) Oct 2022Grape pomace and seeds are important winemaking by-products. Their oils are rich in bioactive compounds such as fatty acids and tocopherols. We have characterized oils...
Grape pomace and seeds are important winemaking by-products. Their oils are rich in bioactive compounds such as fatty acids and tocopherols. We have characterized oils from both by-products from five Spanish grape varieties (Palomino Fino, Pedro Ximénez, Muscat of Alexandria, Tempranillo and Tintilla de Rota). A high content of UFAs was found in all the analyzed samples. Grape pomace oils generally had the same oleic acid (PUFA) content as seed oils, and lower PUFA contents; they also had a markedly higher linolenic acid (PUFA) content, improving the PUFA/PUFA ratio. All the oil studied show good indicators of nutritional quality: low values of the atherogenicity (0.112-0.157 for pomace, 0.097-0.112 for seed) and thrombogenicity indices (0.30-0.35 for pomace, 0.28-0.31 for seed) and high values of the relationship between hypo- and hypercholesterolemic fatty acids (6.93-9.45 for pomace, 9.11-10.54 for seed). Three tocopherols were determined: α-, γ- and δ-tocopherol. Pomace oils have higher relative contents of α- and δ-tocopherol, whereas seed oils have higher relative contents of γ-tocopherol. A significantly higher content of total tocopherols has been found in pomace oil; it is higher in the oils from red varieties of pomace (628.2 and 706.6 mg/kg by-product), and in the oils from pomace containing stems (1686.4 mg/kg by-product). All the oils obtained can be considered as a source of vitamin E, and their consumption is beneficial for health.
Topics: Tocopherols; Fatty Acids; Vitis; gamma-Tocopherol; Spain; Plant Oils; Seeds; Vitamin E; alpha-Linolenic Acid; Oleic Acid
PubMed: 36296576
DOI: 10.3390/molecules27206980 -
Molecular Medicine Reports Jul 2021The phenotypes and mechanisms underlying the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by oleic acid (OA) are not completely...
The phenotypes and mechanisms underlying the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by oleic acid (OA) are not completely understood. Therefore, the aim of the present study was to further elucidate the effects of OA on the proliferation and migration of VSMCs. Using A7r5 cells, the hepatocyte growth factor (HGF) inhibitor PHA665752 and the p38 MAPK inhibitor SB203580 were utilized, and Cell Counting Kit‑8 (CCK‑8) assays, Transwell assays, flow cytometry, ELISAs, western blotting and reverse transcription‑quantitative PCR (RT‑qPCR) were conducted to assess the effects of OA. CCK‑8 assays indicated that OA promoted (at 5 and 50 mol/l) or inhibited (at 800 mol/l) A7r5 cell proliferation in a time‑ and concentration‑dependent manner (P<0.05). Transwell assays revealed that OA also promoted (at 50 mol/l) or inhibited (at 800 mol/l) A7r5 cell migration (P<0.05). Moreover, cell‑cycle analysis identified that 50 mol/l OA reduced the cellular population in the G/G phase and enhanced the cellular population in the S phase (P<0.05), whereas 800 mol/l OA increased the cell number in the G/G phase and decreased the cell number in the S phase (P<0.05). In addition, OA promoted (at 50 mol/l) or inhibited (at 800 mol/l) the expression level of HGF in A7r5 cells, as demonstrated via ELISA, western blotting and RT‑qPCR analyses (P<0.05). It was also found that OA promoted (at 50 mol/l) or inhibited (at 800 mol/l) the expression level of phosphorylated (p)‑p38 in A7r5 cells, as indicated by western blotting (P<0.05). Furthermore, the cell proliferation, migration and HGF expression induced by OA (50 mol/l) were mitigated by treatment with PHA665752 (0.1 mol/l) (P<0.05), and the cell proliferation, migration and p‑p38 expression induced by OA (50 mol/l) were mitigated by SB203580 (2 mol/l) (P<0.05). Thus, the results suggested that OA served a role in the proliferation and migration of VSMCs via HGF and the p38 MAPK pathway. Moreover, the proliferation and migration of VSMCs induced by OA was associated with increased expression levels of HGF and p‑p38. Taken together, OA, HGF and p38 MAPK may be potential therapeutic targets for the treatment of atherosclerosis.
Topics: Animals; Cell Line; Cell Movement; Cell Proliferation; Hepatocyte Growth Factor; Humans; Imidazoles; Indoles; Myocytes, Smooth Muscle; Oleic Acid; Phosphorylation; Pyridines; Signal Transduction; Sulfones; p38 Mitogen-Activated Protein Kinases
PubMed: 33907848
DOI: 10.3892/mmr.2021.12123 -
Molecular Nutrition & Food Research Aug 2022Higher circulating linoleic acid (LA) and muscle-derived tetralinoleoyl-cardiolipin (LA CL) are each associated with decreased cardiometabolic disease risk.... (Randomized Controlled Trial)
Randomized Controlled Trial
SCOPE
Higher circulating linoleic acid (LA) and muscle-derived tetralinoleoyl-cardiolipin (LA CL) are each associated with decreased cardiometabolic disease risk. Mitochondrial dysfunction occurs with low LA CL. Whether LA-rich oil fortification can increase LA CL in humans is unknown. The aims of this study are to determine whether dietary fortification with LA-rich oil for 2 weeks increases: 1) LA in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC); and 2) LA CL in PBMC in adults.
METHODS AND RESULTS
In this randomized controlled trial, adults are instructed to consume one cookie per day delivering 10 g grapeseed (LA-cookie, N = 42) or high oleate (OA) safflower (OA-cookie, N = 42) oil. In the LA-cookie group, LA increases in plasma, erythrocyte, and PBMC by 6%, 7%, and 10% respectively. PBMC and erythrocyte OA increase by 7% and 4% in the OA-cookie group but is unchanged in the plasma. PBMC LA CL increases (5%) while LA OA CL decreases (7%) in the LA-cookie group but are unaltered in the OA-cookie group.
CONCLUSIONS
LA-rich oil fortification increases while OA-oil has no effect on LA CL in adults. Because LA-rich oil fortification reduces cardiometabolic disease risk and increases LA CL, determining whether mitochondrial dysfunction is repaired through dietary fortification is warranted.
Topics: Adult; Cardiolipins; Cardiovascular Diseases; Fatty Acids; Humans; Leukocytes, Mononuclear; Linoleic Acid; Oleic Acid
PubMed: 35596730
DOI: 10.1002/mnfr.202101132 -
Cancer Medicine Jul 2020Several associations between non-genetic biomarkers and colorectal cancer (CRC) risk have been detected, but the strength of evidence and the direction of associations... (Review)
Review
Several associations between non-genetic biomarkers and colorectal cancer (CRC) risk have been detected, but the strength of evidence and the direction of associations are not confirmed. We aimed to evaluate the evidence of these associations and integrate results from different approaches to assess causal inference. We searched Medline and Embase for meta-analyses of observational studies, meta-analyses of randomized clinical trials (RCTs), and Mendelian randomization (MR) studies measuring the associations between non-genetic biomarkers and CRC risk and meta-analyses of RCTs on supplementary micronutrients. We repeated the meta-analyses using random-effects models and categorized the evidence based on predefined criteria. We described each MR study and evaluated their credibility. Seventy-two meta-analyses of observational studies and 18 MR studies on non-genetic biomarkers and six meta-analyses of RCTs on micronutrient intake and CRC risk considering 65, 42, and five unique associations, respectively, were identified. No meta-analyses of RCTs on blood level biomarkers have been found. None of the associations were classified as convincing or highly suggestive, three were classified as suggestive, and 26 were classified as weak. For three biomarkers explored in MR studies, there was evidence of causality and seven were classified as likely noncausal. For the first time, results from both observational and MR studies were integrated by triangulating the evidence for a wide variety of non-genetic biomarkers and CRC risk. At blood level, lower vitamin D, higher homeostatic model assessment-insulin resistance, and human papillomavirus infection were associated with higher CRC risk while increased linoleic acid and oleic acid and decreased arachidonic acid were likely causally associated with lower CRC risk. No association was found convincing in both study types.
Topics: Arachidonic Acid; Biomarkers, Tumor; Colorectal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Insulin Resistance; Linoleic Acid; Mendelian Randomization Analysis; Meta-Analysis as Topic; Micronutrients; Observational Studies as Topic; Oleic Acid; Papillomavirus Infections; Randomized Controlled Trials as Topic; Risk; Vitamin D
PubMed: 32400092
DOI: 10.1002/cam4.3051 -
The Journal of Nutrition Jun 2020The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus,...
BACKGROUND
The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages.
OBJECTIVES
As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid.
METHODS
In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs.
RESULTS
Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals.
CONCLUSION
The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits.
Topics: Animals; Body Weight; Brain; Cognition; Disease Models, Animal; Down Syndrome; Female; Maternal Exposure; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Neurogenesis; Oleic Acid; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; alpha-Linolenic Acid
PubMed: 32243527
DOI: 10.1093/jn/nxaa074 -
Molecules (Basel, Switzerland) Apr 2020A chemo-enzymatic approach for the conversion of oleic acid into azelaic and pelargonic acid is herein described. It represents a sustainable alternative to ozonolysis,...
A chemo-enzymatic approach for the conversion of oleic acid into azelaic and pelargonic acid is herein described. It represents a sustainable alternative to ozonolysis, currently employed at the industrial scale to perform the reaction. Azelaic acid is produced in high chemical purity in 44% isolation yield after three steps, avoiding column chromatography purifications. In the first step, the lipase-mediated generation of peroleic acid in the presence of 35% HO is employed for the self-epoxidation of the unsaturated acid to the corresponding oxirane derivative. This intermediate is submitted to in situ acid-catalyzed opening, to afford 9,10-dihydroxystearic acid, which readily crystallizes from the reaction medium. The chemical oxidation of the diol derivative, using atmospheric oxygen as a stoichiometric oxidant with catalytic quantities of Fe(NO)∙9∙HO, (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), and NaCl, affords 9,10-dioxostearic acid which is cleaved by the action of 35% HO in mild conditions, without requiring any catalyst, to give pelargonic and azelaic acid.
Topics: Biocatalysis; Dicarboxylic Acids; Fatty Acids; Fatty Acids, Unsaturated; Lipase; Molecular Structure; Oleic Acid; Oxidation-Reduction
PubMed: 32325747
DOI: 10.3390/molecules25081882 -
American Journal of Physiology. Cell... May 2022Treatment of mouse preimplantation embryos with elevated palmitic acid (PA) reduces blastocyst development, whereas cotreatment with PA and oleic acid (OA) together...
Treatment of mouse preimplantation embryos with elevated palmitic acid (PA) reduces blastocyst development, whereas cotreatment with PA and oleic acid (OA) together rescues blastocyst development to control frequencies. To understand the mechanistic effects of PA and OA treatment on early mouse embryos, we investigated the effects of PA and OA, alone and in combination, on autophagy during preimplantation development in vitro. We hypothesized that PA would alter autophagic processes and that OA cotreatment would restore control levels of autophagy. Two-cell stage mouse embryos were placed into culture medium supplemented with 100 μM PA, 250 μM OA, 100 μM PA and 250 μM OA, or potassium simplex optimization media with amino acid (KSOMaa) medium alone (control) for 18-48 h. The results demonstrated that OA cotreatment slowed developmental progression after 30 h of cotreatment but restored control blastocyst frequencies by 48 h. PA treatment elevated light chain 3 (LC3)-II puncta and p62 levels per cell whereas OA cotreatment returned to control levels of autophagy by 48 h. Autophagic mechanisms are altered by nonesterified fatty acid (NEFA) treatments during mouse preimplantation development in vitro, where PA elevates autophagosome formation and reduces autophagosome degradation levels, whereas cotreatment with OA reversed these PA effects. Autophagosome-lysosome colocalization only differed between PA and OA alone treatment groups. These findings advance our understanding of the effects of free fatty acid exposure on preimplantation development, and they uncover principles that may underlie the associations between elevated fatty acid levels and overall declines in reproductive fertility.
Topics: Animals; Autophagy; Blastocyst; Culture Media; Fatty Acids, Nonesterified; Mice; Oleic Acid; Palmitic Acid
PubMed: 35319901
DOI: 10.1152/ajpcell.00414.2021