ABSTRACT
AIMS/HYPOTHESIS: Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS: In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS: SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCÉ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION: Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION: ClinicalTrials.gov .NCT01736202. FUNDING: German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.
Subject(s)
Dietary Fats/administration & dosage , Insulin Resistance/physiology , Muscle, Skeletal/metabolism , Oleic Acid/administration & dosage , Palmitates/administration & dosage , Adult , Blood Glucose/metabolism , Calorimetry , Cross-Over Studies , Diglycerides/blood , Fatty Acids/blood , Female , Glucose Clamp Technique , Healthy Volunteers , Humans , Male , Palm Oil/administration & dosage , Protein Kinase C/blood , Safflower Oil/administration & dosage , Young AdultABSTRACT
There is growing evidence that greater than homeostatic blood concentrations of nonesterified fatty acids (NEFAs) and ß-hydroxybutyrate (BHBA) have negative consequences on dairy cow's fertility, but effects on cell homeostasis in the reproductive system is not completely understood. In this study, lipids accumulation, reactive oxygen species (ROS) concentrations, abundance of gene transcripts, and immunofluorescence signal of H3K4me3 and H3K9me3 were evaluated in endometrial epithelial cells of cattle cultured with NEFAs (Oleic (OA), Stearic (SA) and Palmitic (PA) acids), BHBA, NEFAs + BHBA or each of the three NEFAs alone. The cellular lipids were in greater concentrations as a result of NEFAs + BHBA, NEFAs, SA or OA supplementation, but not by BHBA or PA. The ROS concentrations were greater when there were treatments with NEFAs + BHBA, NEFAs or BHBA. The relative mRNA abundance for genes involved in the regulation of apoptosis (XIAP), glucose transport (GLUT3), and DNA methylation (DNMT1) were greater when there were NEFAs + BHBA, but not NEFAs, BHBA, OA, SA or PA treatments. The immunofluorescence signal for H3K9me3 was greater when there were NEFAs + BHBA, NEFAs or PA, but not by BHBA, OA or SA treatments. These findings indicate that NEFAs and BHBA have an additive effect on endometrial cells of cattle by altering epigenetic markers and the expression of genes controlling important cellular pathways. Furthermore, there was cellular lipid accumulation and increased H3K9me3 in cultured bovine endometrial cells that was mainly induced by OA and PA treatments, respectively.
Subject(s)
Endometrium/metabolism , Fatty Acids, Nonesterified/administration & dosage , Histones/metabolism , 3-Hydroxybutyric Acid/administration & dosage , 3-Hydroxybutyric Acid/blood , Animals , Cattle , Endometrium/cytology , Epithelial Cells/metabolism , Fatty Acids, Nonesterified/blood , Female , Fluorescent Antibody Technique , Oleic Acid/administration & dosage , Palmitic Acid/administration & dosage , Reactive Oxygen Species/metabolism , Stearic Acids/administration & dosageABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Cutaneous inflammatory diseases, such as irritant contact dermatitis, are usually treated with topical corticosteroids, which cause systemic and local adverse effects limiting their use. Thus, the discovery of new therapeutic alternatives able to effectively treat skin inflammatory disorders, without causing adverse effects, is urgently needed. AIM OF THE STUDY: To investigate the topical anti-inflammatory effect of oleic acid (OA), a monounsaturated fatty acid, into Pemulen® TR2-based semisolid dosage forms, employing a croton oil-induced irritant contact dermatitis model in mice. MATERIALS AND METHODS: Male Swiss mice were submitted to skin inflammation protocols by acute and repeated applications of croton oil. The anti-inflammatory activity of Pemulen® TR2 hydrogels containing OA was evaluated by assessing oedema, inflammatory cell infiltration, and pro-inflammatory cytokine IL-1ß levels. The mechanisms of action of OA were evaluated using cytokine IL-1ß application or pretreatment with the glucocorticoid antagonist mifepristone. Possible toxic effects of OA were also assessed. RESULTS: Pemulen® TR2 3% OA inhibited the acute ear oedema [maximal inhibition (Imax) = 76.41 ± 5.69%], similarly to dexamethasone (Imax = 84.94 ± 2.16%), and also inhibited ear oedema after repeated croton oil application with Imax = 85.75 ± 3.08%, similar to dexamethasone (Imax = 81.03 ± 4.66%) on the day 7 of the experiment. Croton oil increased myeloperoxidase activity, which was inhibited by Pemulen® TR2 3% OA (Imax = 71.37 ± 10.97%) and by 0.5% dexamethasone (Imax = 96.31 ± 3.73%). Pemulen® TR2 3% OA also prevented the increase in pro-inflammatory cytokine IL-1ß levels induced by croton oil (Imax = 94.18 ± 12.03%), similar to 0.5% dexamethasone (Imax = 87.21 ± 10.58%). Besides, both Pemulen® TR2 3% OA and 0.5% dexamethasone inhibited IL-1ß-induced ear oedema with an Imax of 80.58 ± 2.45% and 77.46 ± 1.92%, respectively. OA and dexamethasone anti-inflammatory effects were prevented by 100% and 91.43 ± 5.43%, respectively, after pretreatment with mifepristone. No adverse effects were related to Pemulen® TR2 3% OA administration. CONCLUSIONS: OA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Dermatitis, Irritant/prevention & control , Oleic Acid/pharmacology , Skin/drug effects , Administration, Cutaneous , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/toxicity , Croton Oil , Dermatitis, Irritant/etiology , Dermatitis, Irritant/metabolism , Dermatitis, Irritant/pathology , Disease Models, Animal , Inflammation Mediators/metabolism , Interleukin-1beta/metabolism , Male , Mice , Oleic Acid/administration & dosage , Oleic Acid/toxicity , Skin/metabolism , Skin/pathologyABSTRACT
OBJECTIVES: Plant oil for cooking typically provides 40% to 50% of dietary fat, 65% of linoleic acid, 44% of α-linolenic acid and 41% of oleic acid in the Chinese diet. However, the comparative effects of fatty acids derived from plant oil on cardiovascular risk factors in Chinese are still inconclusive. Hence, the aim of this study is to investigate whether cardiovascular risk factors are altered depending on various types of plant oils such as peanut oil rich in oleic acid, corn oil rich in linoleic acid, and blend oil fortified by α-linolenic acid. DESIGN: A randomized, double-blinded, parallel-designed trial. SETTING: The First and the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. PARTICIPANTS: A total of 251 volunteers with fasting blood total cholesterol between 5.13 and 8.00 mmol L-1 were enrolled. INTERVENTION: Volunteers received peanut oil, corn oil or blend oil to use for cooking for one year. MAIN OUTCOME MEASURES: The erythrocyte membrane fatty acid composition, fasting plasma lipids, glucose and insulin concentrations and high sensitivity C-reactive protein (hsCRP) levels were measured before, during and after the intervention. The level of α-linolenic acid in erythrocyte membranes was significantly increased in the blend oil group after the intervention (P < 0.001). The level of other fatty acids did not show any statistically significant differences between the three groups. No significant differences were observed in the concentrations of fasting plasma lipids, hsCRP, glucose, and insulin among the three groups using different types of plant oils. CONCLUSIONS: The results suggest that although ingesting cooking oil with different fatty acid composition for one year could change erythrocyte membrane fatty acid compositions, it did not significantly modify cardiovascular risk factors in moderately hypercholesteremic people.
Subject(s)
Diet, Fat-Restricted/methods , Dietary Fats/administration & dosage , Fatty Acids/administration & dosage , Hypercholesterolemia/diet therapy , Plant Oils/administration & dosage , Adult , Aged , Asian People , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , China , Cholesterol/blood , Corn Oil/administration & dosage , Corn Oil/chemistry , Double-Blind Method , Fasting/blood , Fatty Acids/chemistry , Female , Heart Disease Risk Factors , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Linoleic Acid/administration & dosage , Male , Middle Aged , Oleic Acid/administration & dosage , Peanut Oil/administration & dosage , Peanut Oil/chemistry , Plant Oils/chemistry , alpha-Linolenic Acid/administration & dosageABSTRACT
In this study, rice starch-oleic acid complex with well-controlled digestibility was chosen as a supplementary diet for rats fed with high fat diet. Our results demonstrated that rice starch-oleic acid complex supplementation significantly decreased body weight, improved serum lipid profiles, hepatic metabolism and altered the composition of gut microbiota of rats, which might be related to the higher resistant starch (RS) level. Interestingly, rice starch-oleic acid complex supplementation contributed to the proliferation and growth of butyrate-producing bacteria. The Spearman's correlation analysis revealed that the genus Turicibacter and Romboutsia genus were positively correlated to HDL-c and SOD level. Meanwhile, based on the metagenomic data, Bifidobacteria genus might be a main primary degrader after rice starch-oleic acid complex intake, which was associated with the changes of key starch-degradation enzymes. Overall, our results provided basic data for the rational design of rice starch-based foods with nutritional functions and physiological benefits.
Subject(s)
DNA, Bacterial/genetics , Gastrointestinal Microbiome/drug effects , Obesity/prevention & control , Oleic Acid/administration & dosage , Resistant Starch/administration & dosage , Actinobacteria/classification , Actinobacteria/drug effects , Actinobacteria/genetics , Actinobacteria/isolation & purification , Animals , Bacteroidetes/classification , Bacteroidetes/drug effects , Bacteroidetes/genetics , Bacteroidetes/isolation & purification , Butyrates/metabolism , Cholesterol, LDL/metabolism , Diet, High-Fat/adverse effects , Firmicutes/classification , Firmicutes/drug effects , Firmicutes/genetics , Firmicutes/isolation & purification , Gastrointestinal Microbiome/genetics , Gene Expression , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Lipid Metabolism/drug effects , Lipid Metabolism/genetics , Liver/drug effects , Liver/metabolism , Male , Obesity/etiology , Obesity/genetics , Obesity/microbiology , Phylogeny , Proteobacteria/classification , Proteobacteria/drug effects , Proteobacteria/genetics , Proteobacteria/isolation & purification , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolismABSTRACT
Obesity continues to be a growing health concern around the world, and elevated levels of free fatty acids as a result of high-fat intake might play a role in neuroendocrine alterations leading to obesity. However, it is unclear how fatty acids affect neuroendocrine functions and energy metabolism. Since hypothalamic monoamines play a crucial role in regulating neuroendocrine functions relating to energy balance, we investigated the direct effects of oleic acid on hypothalamic monoamines and hypothesized that oleic acid would activate peroxisome proliferator-activated receptor alpha (PPAR-α), a nuclear transcription factor involved with fatty acid metabolism, to affect monoamines. We also hypothesized that this response would be subdued in diet-induced obesity (DIO). To test these hypotheses, hypothalami from Sprague Dawley and DIO rats were incubated with 0 (Control), 0.00132 mM, 0.132 mM, 1.32 mM oleic acid, 50 µM MK 886 (a selective PPAR- α antagonist), or oleic acid + MK 886 in Krebs Ringers Henseleit (KRH) solution. HPLC-EC was used to measure monoamine levels in perfusates. Oleic acid produced a significant increase in norepinephrine, dopamine, and serotonin levels in a dose-dependent manner, and incubation with MK886 blocked these effects. The effect of oleic acid on hypothalamic monoamines was attenuated in DIO rats. These findings suggest that PPARα probably plays an essential role in fatty acid sensing in the hypothalamus, by affecting monoamine efflux and DIO rats are resistant to the effects of oleic acid.
Subject(s)
Hypothalamus/drug effects , Obesity/physiopathology , Oleic Acid/pharmacology , PPAR alpha/metabolism , Animals , Diet, High-Fat/adverse effects , Dopamine/metabolism , Dose-Response Relationship, Drug , Fatty Acids, Nonesterified/metabolism , Hypothalamus/metabolism , Indoles/pharmacology , Male , Norepinephrine/metabolism , Oleic Acid/administration & dosage , Rats , Rats, Sprague-Dawley , Serotonin/metabolismABSTRACT
Early feeding trials using peanut meal prepared from normal-oleic peanuts helped to identify peanuts as a suitable alternative feed ingredient for poultry. Yet no studies to date have examined the use of high-oleic peanuts (HO-PN) as a feed ingredient for meat type chickens. Therefore, this study aimed to determine the effect of feeding whole unblanched HO-PN on the fatty acid profile of the meat produced from broilers. At hatch male chicks were randomly placed in raised wire cages, in 10 replicate pens per treatment with 10 chicks per pen, and fed with one of the 3 isocaloric, isonitrogenous diets ad libitum for 42 days: (1) conventional control of soybean meal + corn, (2) 10 to 12% HO-PN and corn diet, or (3) control diet spiked with ≈6.0% oleic acid oil. All body weights (BW) were collected, and broiler selection for processing was determined by individual BW within one-half a standard deviation of the experiment 42-D mean BW, with one bird selected per pen (10 replicate pens per treatment, 3 treatments, 10 birds selected per treatment, yielding a total sample size of 30 birds). Performance was determined weekly and breast samples were analyzed for fatty acid and amino acid profile. All data was analyzed using analysis of variance, with t-test mean comparisons at P < 0.05. BW were similar between broilers fed the HO-PN and control diet, while feed conversion ratio of broilers fed the HO-PN diet was significantly higher at weeks 2, 4, and 6 in comparison to the other treatments (P ≤ 0.03). Broilers fed with HO-PN diet had reduced carcass and pectoralis major weights in comparison to the other treatments. Chicken breast from broilers fed the HO-PN diet had significantly reduced saturated and trans fatty acid content in comparison to the controls (P ≤ 0.0002). Although additional studies must be conducted, this study suggests that feeding whole unblanched HO-PN to broiler chickens may serve as a means to enrich the meat produced with unsaturated fatty acids.
Subject(s)
Arachis/chemistry , Chickens/metabolism , Fatty Acids/metabolism , Oleic Acid/metabolism , Animal Feed/analysis , Animals , Chickens/growth & development , Diet/veterinary , Dietary Supplements/analysis , Male , Oleic Acid/administration & dosage , Random AllocationABSTRACT
Loss of retinal function due to manifestation of chronic inflammation and oxidative stress in hyperglycemia is well addressed. However, the effect of hyperlipidemia on retinal inflammation and microvascular integrity, and the modulatory effects of oxidation-stable oleic acid and long-chain n-3 fatty acids have never been addressed. The objective of this investigation was to assess the retinoprotective effect of oxidation stable oleic acid and oxidation-susceptible EPA + DHA on retinal inflammation and microvascular integrity, under hyperlipidemic conditions. Male Wistar rats were fed with control (7.0% lard), high-fat (35.0% lard), high-fat with fish oil (17.5% fish oil + 17.5% lard), high-fat with olive oil (17.5% olive oil + 17.5% lard), and high-fat with fish oil and olive oil (11.66% fish oil + 11.66% of olive oil + 11.66% of lard) diet for 90 days. Systemic and retinal inflammation, as measured by eicosanoids and cytokines, retinal expression of NF-kB, capillary degeneration, and pericyte loss, were assessed. Hyperlipidemia significantly (p < 0.05) increased the markers of inflammation (PGE2, LTB4, LTC4, IL-1ß, MCP-1, and TNF-α) in serum and retina. Besides, the retinal NF-kB-p65 expression, capillary degeneration, and pericyte loss were significantly (p < 0.05) increased under hyperlipidemic conditions. Dietary incorporation of oleic acid and EPA + DHA significantly (p < 0.05) suppressed hyperlipidemia-induced effects in the retina. In conclusion, hyperlipidemia causes retinal aberrations by compromising the balance in the inflammatory response and microvascular integrity. Dietary incorporation of oleic acid and long-chain n-3 fatty acids prevents hyperlipidemia-induced aberrations in the retina.
Subject(s)
Fatty Acids, Omega-3/administration & dosage , Hyperlipidemias/metabolism , Inflammation Mediators/metabolism , Microvessels/metabolism , Oleic Acid/administration & dosage , Retina/metabolism , Animals , Biomarkers/metabolism , Diet, High-Fat/adverse effects , Disease Models, Animal , Fish Oils/administration & dosage , Hyperlipidemias/diet therapy , Hyperlipidemias/etiology , Inflammation/diet therapy , Inflammation/etiology , Inflammation/metabolism , Inflammation Mediators/antagonists & inhibitors , Male , Microvessels/drug effects , Olive Oil/administration & dosage , Rats , Rats, Wistar , Retina/drug effects , Retinal Vessels/drug effects , Retinal Vessels/metabolismABSTRACT
Saturated fatty acids, such as palmitate, lead to circadian disruption. We aimed at studying the effect of low doses of palmitate on circadian metabolism and to decipher the mechanism by which fatty acids convey their effect in adipocytes. Mice were fed non-obesogenic doses of palm or olive oil and adipocytes were treated with palmitate and oleate. Cultured adipocytes treated with oleate showed increased AMPK activity and induced the expression of mitochondrial genes indicating increased fatty acid oxidation, while palmitate increased ACC activity and induced the expression of lipogenic genes, indicating increased fatty acid synthesis. Low doses of palmitate were sufficient to alter circadian rhythms, due to changes in the expression and/or activity of key metabolic proteins including GSK3ß and AKT. Palmitate-induced AKT and GSK3ß activation led to the phosphorylation of BMAL1 that resulted in low levels as well as high amplitude of circadian clock expression. In adipocytes, the detrimental metabolic alteration of palmitate manifests itself early on even at non-obesogenic levels. This is accompanied by modulating BMAL1 expression and phosphorylation levels, which lead to dampened clock gene expression.
Subject(s)
Adipocytes/metabolism , Circadian Clocks/drug effects , Oleic Acid/administration & dosage , Palmitic Acid/administration & dosage , 3T3-L1 Cells , AMP-Activated Protein Kinases/genetics , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Adipocytes/cytology , Adipocytes/drug effects , Animals , Cells, Cultured , Gene Expression Regulation/drug effects , Male , Mice , Mitochondrial Proteins/genetics , Oleic Acid/pharmacology , Olive Oil/chemistry , Palm Oil/chemistry , Palmitic Acid/pharmacology , Phosphorylation/drug effectsABSTRACT
Unhealthy dietary patterns are important risk factors for metabolic syndrome (MS), which is associated with gut microbiota disorder. High oleic acid peanut oil (HOPO) and extra virgin olive oil (EVOO), considered as healthy dietary oil, are rich in oleic acid and bioactive phytochemicals, yet efficacy of MS prevention and mechanisms linking to gut microbiota remain obscure. Herein, we investigated HOPO and EVOO supplementation in attenuating diet-induced MS, and the potential mechanisms focusing on modulation of gut microbiota. Physiological, histological and biochemical parameters and gut microbiota profiles were compared among four groups fed respectively with the following diets for 12 weeks: normal chow diet with ordinary drinking water, high-fat diet with fructose drinking water, HOPO diet with fructose drinking water, and EVOO diet with fructose drinking water. HOPO or EVOO supplementation exhibit significant lower body weight gain, homeostasis model assessment-insulin resistance (HOMA-IR), and reduced liver steatosis. HOPO significantly reduced cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) level, while EVOO reduced these levels without significant difference. HOPO and EVOO prevented gut disorder and significantly increased ß-diversity and abundance of Bifidobacterium. Moreover, HOPO significantly decreased abundance of Lachnospiraceae and Blautia. These findings suggest that both HOPO and EVOO can attenuate diet-induced MS, associated with modulating gut microbiota.
Subject(s)
Gastrointestinal Microbiome , Metabolic Syndrome/diet therapy , Metabolic Syndrome/microbiology , Oleic Acid/administration & dosage , Olive Oil/administration & dosage , Peanut Oil/administration & dosage , Animals , Diet, High-Fat , Dietary Supplements , Disease Models, Animal , Male , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
This experiment was conducted to determine the effects of stearic acid (SA; C18:0) or rumen-protected oleic acid (OA; C18:1 cis-9) on milk performance and energy partitioning of early lactation cows when supplemented in diets with low and high level of rumen unsaturated fatty acids (RUFA). In low RUFA experiment (LRUFA), FA supplement rich in either SA or calcium salts OA was added to a basal diet with a low concentration of RUFA (0.75% vs. 1.4%, LRUFA-SA vs. LRUFA-OA). In high RUFA experiment (HRUFA), 2% soybean oil was added to the diet fed in the LRUFA experiment. In each experiment, 30 multiparous cows were blocked by parity and predicted transmitting ability for milk yield and were randomly fed 1 of 2 treatment diets from 2 to 13 wk postpartum. In the LRUFA experiment, LRUFA-SA had 2.4 kg/d more dry matter intake (DMI) (P < 0.01), 3.8 kg/d more energy-corrected milk (P < 0.01), and 0.3% units more milk fat percentage (P < 0.01) and 0.2 kg/d more milk fat yield (P < 0.01). Dietary treatments did not affect body weight, energy balance, and energy intake partitioning into milk, maintenance, and body tissues (P > 0.1). In the HRUFA experiment, HRUFA-SA had 1.4 kg/d more DMI (P = 0.03) but similar milk and milk components yields (P > 0.1). HRUFA-SA had a tendency to gain more body weight (P = 0.07) and had more positive energy balance (P = 0.01) and decreased gross feed efficiency (milk yield/DMI) (P = 0.01). Consistently, HRUFA-SA increased intake energy partitioning into body tissues (P = 0.02) and decreased energy partitioning into milk (P = 0.01). In summary, SA supplementation had more DMI relative to OA, but the effects on milk and milk fat production were different and affected by the level of RUFA in the basal diet. In application, SA supplementation was more effective to improve milk production when included in the basal diet with the low RUFA.
Subject(s)
Cattle/physiology , Dietary Supplements/analysis , Energy Metabolism/drug effects , Fatty Acids, Unsaturated/administration & dosage , Milk/metabolism , Oleic Acid/administration & dosage , Stearic Acids/administration & dosage , Animals , Body Weight , Diet/veterinary , Female , Glycolipids/analysis , Glycoproteins/analysis , Lactation , Lipid Droplets , Milk/chemistry , Postpartum Period , Pregnancy , Rumen/metabolism , Soybean Oil/administration & dosageABSTRACT
Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions.
Subject(s)
Caenorhabditis elegans Proteins/metabolism , Longevity/physiology , Transcription Factors/metabolism , Animals , Caenorhabditis elegans , Cold Temperature , Dietary Supplements , Fatty Acid Desaturases/metabolism , Homeostasis , Lipid Metabolism , Oleic Acid/administration & dosage , Proteostasis , Transcriptional ActivationABSTRACT
Motor neuron damage caused by diseases, traumatic insults or de-afferentation of the spinal cord is often incurable due to the poor intrinsic regenerative capacity. Moreover, regenerated peripheral nerves often do not reach normal functionality. Here, we investigated cardiolipin in the process of neuro-differentiation, since cardiolipin is closely linked to the mitochondrial energy supply in cells. The NSC-34 hybrid cell line, produced by fusing neuroblastoma cells with primary spinal cord motor neurons, was used, since it shares several morphological and physiological characteristics with mature primary motor neurons. Their neuro-differentiation was supported by switching from normal to differentiation medium or by fatty acid supplementation. Differentiation was evaluated by measuring neurite-sprouting parameters and PPARα expression. Cellular fatty acid distribution was analyzed to indicate changes in lipid metabolism during differentiation. Cardiolipin was characterized by acyl-chain composition and the distribution of molecular cardiolipin species. Both, the switch from normal to differentiation medium as well as the administration of palmitic and oleic acid promoted neuro-differentiation. Stimulated differentiation was accompanied by changes in cardiolipin content and composition. The positive correlation between neuro-differentiation and concentration of those molecular cardiolipin species containing palmitic and oleic acid implied a link between differentiation of NSC-34 cells and cardiolipin metabolism. We further demonstrated the impact of cellular lipid metabolism, and particularly cardiolipin metabolism, during and NSC-34 neuritogenesis. Thus, cardiolipin may represent a new therapeutic target for axon regeneration after peripheral nerve injuries or when axon sprouting is required to compensate for motor neuron loss in response to aging and/or disease.
Subject(s)
Cardiolipins/metabolism , Cell Differentiation , Mitochondria/metabolism , Motor Neurons/metabolism , Spinal Cord/metabolism , Animals , Cell Line, Tumor , Cell Proliferation , Cell Survival , Mice , Neurites/metabolism , Oleic Acid/administration & dosage , PPAR alpha/metabolism , Palmitic Acid/administration & dosageABSTRACT
BACKGROUND: High-oleic (HO) seed oils are being introduced as replacements for trans fatty acid (TFA)-containing fats and oils. Negative health effects associated with TFAs led to their removal from the US Generally Recognized As Safe list. HO oils formulated for use in food production may result in changes in fatty acid intake at population levels. Objectives: The purposes of this study were to 1) identify major food sources of soybean oil (SO) and canola oil (CO), 2) estimate effects of replacing SO and CO with HO varieties on fatty acid intake overall and by age and sex strata, and 3) compare predicted intakes with the Dietary Reference Intakes and Adequate Intakes (AIs) for the essential fatty acids (EFAs) α-linolenic acid (ALA) and linoleic acid (LA). Design: Food and nutrient intakes from NHANES waves 2007-2008, 2009-2010, 2011-2012, and 2013-2014 in 21,029 individuals aged ≥20 y were used to model dietary changes. We estimated the intake of fatty acid with the replacement of HO-SO and HO-CO for commodity SO and CO at 10%, 25%, and 50% and evaluated the potential for meeting the AI at these levels. RESULTS: Each modeling scenario decreased saturated fatty acids (SFAs), although intakes remained greater than recommended for all age and sex groups. Models of all levels increased the intake of total monounsaturated fatty acids (MUFAs), especially oleic acid, and decreased the intake of total polyunsaturated fatty acids (PUFAs), particularly LA and ALA. Replacement of traditional with HO oils at 25-50% places specific adult age and sex groups at risk of not meeting the AI for LA and ALA. Conclusions: The replacement of traditional oils with HO varieties will increase MUFA intake and reduce both SFA and PUFA intakes, including EFAs, and may place specific age and sex groups at risk of inadequate LA and ALA intake.
Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/administration & dosage , Fatty Acids/administration & dosage , Oleic Acid/administration & dosage , Rapeseed Oil/analysis , Soybean Oil/analysis , Adult , Aged , Diet , Dietary Fats, Unsaturated/analysis , Fatty Acids/analysis , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Unsaturated/analysis , Female , Humans , Lactation , Linoleic Acid/administration & dosage , Linoleic Acid/deficiency , Male , Middle Aged , Nutrition Policy , Nutrition Surveys , Oleic Acid/analysis , Pregnancy , Risk Factors , Trans Fatty Acids/administration & dosage , Trans Fatty Acids/analysis , alpha-Linolenic Acid/administration & dosage , alpha-Linolenic Acid/deficiencyABSTRACT
In this study, we compared the impact of administration of size-calibrated lipid emulsions prepared with either synthetic or natural emulsifiers on the post-absorptive plasma triacylglycerol responses in rats. We did this using four types of size-calibrated (10 µm diameter) and metastable (3 days) emulsions with 20% of an oleic acid-rich sunflower oil and 1% of either synthetic emulsifiers (Tween 80 or sodium 2-stearoyl-lactylate) or two proteins (ß-lactoglobulin or sodium caseinate). An oral fat tolerance test was performed in fasted rats by oral administration of each of these formulations in continuous or emulsified forms. Kinetic parameters (AUC0-inf., AUC0-6h, Cmax, Tmax, and T1/2) for the description of the plasma triacylglycerol responses were calculated. AUC0-6h and AUC0-inf. calculated for the protein groups were significantly lower than those of the control and the synthetic groups. These lower values were associated with significant decreases in the Cmax, exacerbated by the emulsion form and with marked decreases in the Tmax as compared to the control group. T1/2 values were differentially affected by the lipid administration forms and by the nature of the emulsifiers. As compared with the control group, T1/2 was largely increased in the sodium stearoyl-2-lactylate group, but on the contrary, largely lowered in the casein group. We concluded that the use of proteins as natural emulsifiers in lipid emulsions decreased the magnitude of post-prandial triacylglycerolemia for the same amount of ingested lipids, when the emulsion size is controlled for. Proteins could be a promising alternative to the widespread use of synthetic emulsifiers in the food industry.
Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Dietary Proteins/chemistry , Emulsifying Agents/chemistry , Food Additives/chemistry , Hypertriglyceridemia/prevention & control , Oleic Acid/administration & dosage , Sunflower Oil/administration & dosage , Animals , Area Under Curve , Caseins/adverse effects , Caseins/chemistry , Dietary Fats, Unsaturated/adverse effects , Dietary Fats, Unsaturated/metabolism , Dietary Proteins/adverse effects , Digestion , Emulsifying Agents/adverse effects , Emulsions , Food Additives/adverse effects , Half-Life , Hypertriglyceridemia/blood , Hypertriglyceridemia/etiology , Intestinal Absorption , Lactoglobulins/adverse effects , Lactoglobulins/chemistry , Male , Oleic Acid/adverse effects , Oleic Acid/chemistry , Oleic Acid/metabolism , Particle Size , Polysorbates/adverse effects , Polysorbates/chemistry , Postprandial Period , Rats, Wistar , Stearates/adverse effects , Stearates/chemistry , Sunflower Oil/adverse effects , Sunflower Oil/chemistry , Sunflower Oil/metabolism , Triglycerides/bloodABSTRACT
Previous studies demonstrate humans can detect fatty acids via specialized sensors on the tongue, such as the CD36 receptor. Genetic variation at the common single nucleotide polymorphism rs1761667 of CD36 has been shown to differentially impact the perception of fatty acids, but comparative data among different ethnic groups are lacking. In a small cohort of Caucasian and East Asian young adults, we investigated if: (1) participants could detect oleic acid (C18:1) added to safflower oil emulsions at a constant ratio of 3% (w/v); (2) supplementation of oleic acid to safflower oil emulsions enhanced perception of fattiness and creaminess; and (3) variation at rs1761667 influenced oleic acid detection and fat taste perception. In a 3-alternate forced choice test, 62% of participants detected 2.9 ± 0.7 mM oleic acid (or 0.08% w/v) in a 2.8% safflower oil emulsion. Supplementation of oleic acid did not enhance fattiness and creaminess perception for the cohort as a whole, though East Asians carrying the GG genotype perceived more overall fattiness and creaminess than their AA genotype counterparts (P < 0.001). No differences were observed for the Caucasians. These preliminary findings indicate that free oleic acid can be detected in an oil-in-water emulsion at concentrations found in commercial oils, but it does not increase fattiness or creaminess perception. Additionally, variation at rs1761667 may have ethnic-specific effects on fat taste perception.
Subject(s)
CD36 Antigens/genetics , Ethnicity , Oleic Acid/administration & dosage , Safflower Oil/administration & dosage , Taste Perception/genetics , Adult , Body Composition , Body Mass Index , Emulsions , Female , Food Additives/administration & dosage , Food Additives/analysis , Gene Frequency , Humans , Lipid Metabolism , Male , Oleic Acid/analysis , Polymorphism, Single Nucleotide , Safflower Oil/chemistry , Taste , Young AdultABSTRACT
Chickens can hepatically synthesize eicosapentaenoic acid (20:5 n-3) and docosahexaenoic acid (22:6 n-3) from α-linolenic acid (ALA; 18:3 n-3); however, the process is inefficient and competitively inhibited by dietary linoleic acid (LNA; 18:2 n-6). In the present study, the influence of dietary high-oleic acid (OLA; 18:1 n-9) soybean oil (HOSO) on egg and tissue deposition of ALA and n-3 polyunsaturated fatty acids (PUFA) synthesized from dietary ALA was investigated in laying hens fed a reduced-LNA base diet supplemented with high-ALA flaxseed oil (FLAX). We hypothesized that reducing the dietary level of LNA would promote greater hepatic conversion of ALA to very long-chain (VLC; >20C) n-3 PUFA, while supplemental dietary HOSO would simultaneously further enrich eggs with OLA without influencing egg n-3 PUFA contents. Nine 51-week-old hens each were fed 0, 10, 20, or 40 g HOSO/kg diet for 12 weeks. Within each group, supplemental dietary FLAX was increased every 3 weeks from 0 to 10 to 20 to 40 g/kg diet. Compared to controls, dietary FLAX maximally enriched the total n-3 and VLC n-3 PUFA contents in egg yolk by 9.4-fold and 2.2-fold, respectively, while feeding hens 40 g HOSO/kg diet maximally attenuated the yolk deposition of ALA, VLC n-3 PUFA, and total n-3 PUFA by 37, 15, and 32%, respectively. These results suggest that dietary OLA is not neutral with regard to the overall process by which dietary ALA is absorbed, metabolized, and deposited into egg yolk, either intact or in the form of longer-chain/more unsaturated n-3 PUFA derivatives.
Subject(s)
Animal Feed , Egg Yolk/chemistry , Egg Yolk/drug effects , Fatty Acids, Omega-3/analysis , Linseed Oil/administration & dosage , Oleic Acid/pharmacology , Soybean Oil/pharmacology , Animals , Chickens , Dietary Supplements , Linseed Oil/chemistry , Oleic Acid/administration & dosage , Soybean Oil/administration & dosageABSTRACT
BMI-specific differences in food choice and energy intake have been suggested to modulate taste perception. However, associations between body composition and fat taste sensitivity are controversial. The objective of this study was to examine the association between body composition, dietary intake and detection thresholds of four fatty stimuli (oleic acid, paraffin oil, canola oil, and canola oil spiked with oleic acid) that could be perceived via gustatory and/or textural cues. In 30 participants, fat detection thresholds were determined in a repeated measurements design over twelve days. Weight status was examined by measuring the participants' BMI, waist circumference and waist-to-hip ratio. The habitual food intake was assessed via several questionnaires and twelve, non-consecutive 24-hour food diaries. In this study, a negative correlation was found between fat detection thresholds and the intake of food rich in vitamins and fibre. Moreover, a positive correlation was identified between the intake of high-fat food and fat detection thresholds. No differences in fat detection thresholds were observed due to variations in BMI or waist-to-hip ratio. These findings indicate that a regular intake of fatty foods might decrease an individuals' perceptual response to fats which might lead to excess fat intake on the long term.
Subject(s)
Diet , Dietary Fats , Fast Foods , Taste Perception , Taste Threshold , Adolescent , Adult , Body Composition , Body Mass Index , Body Weight , Choice Behavior , Diet Records , Dietary Fats/administration & dosage , Dietary Fiber/administration & dosage , Female , Food Preferences , Health Behavior , Humans , Male , Micronutrients/administration & dosage , Middle Aged , Nutrition Assessment , Oils/administration & dosage , Oleic Acid/administration & dosage , Paraffin/administration & dosage , Rapeseed Oil/administration & dosage , Surveys and Questionnaires , Taste , Waist Circumference , Young AdultABSTRACT
Precise delivery of antineoplastic drugs to specific tumor region has drawn much attention in recent years. Herein, a light/magnetic hyperthermia triggered drug delivery with multiple functionality is designed based on methotrexate (MTX) modified thermo-sensitive magnetoliposomes (MTX-MagTSLs). In this system, MTX and oleic acid modified magnetic nanoparticles (MNPs) can be applied in biological and magnetic targeting. Meanwhile, lipophilic fluorescent dye Cy5.5 and MNPs are encapsulated into the bilayer of liposomes, which can not only achieve dual-imaging effect to verify the MTX-MagTSLs accumulation in tumor region, but also provide an appropriate laser irradiation region to release Doxorubicin (Dox) under alternating magnetic field (AMF). Both in vitro and in vivo results revealed that MTX-MagTSLs possessed an excellent targeting ability towards HeLa cells and HeLa tumor-bearing mice. Furthermore, the heating effect of MTX-MagTSLs was amplified 4.2-fold upon combination with AMF and local precise near-infrared laser irradiation (808nm) (DUAL-mode) to rapidly reach the phase change temperature (Tm) of MTX-MagTSLs in 5min compared with either AMF or laser stimulation alone, resulting in a significantly enhanced release of Dox at tumor region and precise cancer synergetic theranostics.
Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Hyperthermia, Induced , Light , Magnetic Fields , Methotrexate/administration & dosage , Nanoparticles/administration & dosage , A549 Cells , Animals , Female , HeLa Cells , Humans , Iron/administration & dosage , Liposomes , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms/diagnosis , Neoplasms/drug therapy , Oleic Acid/administration & dosage , Rats, Sprague-Dawley , Theranostic NanomedicineABSTRACT
Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in lipid metabolism and is expressed in cumulus cells. The objective of the present study was to evaluate the effect of SCD1 inhibition in human cumulus cells on triglyceride content, steroidogenesis, and oocyte in vitro maturation. Human cumulus cells were exposed to SCD1 inhibitor CAY10566 (SCDinhib) alone or in combination with oleic acid in primary culture. The SCDinhib markedly suppressed triglyceride accumulation (-47%, P = .01), aromatase gene expression (-36%, P = .02), and estradiol production (-49%, P = .01) even at a dose not affecting cell viability and apoptosis. Human immature oocytes at the germinal vesicle (GV) stage were cocultured with pretreated cumulus cells. The rate of oocytes reaching the metaphase II stage was significantly lower in coculture with SCDinhib-treated cumulus cells than with control cumulus cells (-18%, P < .01), which recovered by oleic acid supplementation. This finding on in vitro maturation rate was also reproducible with mouse GV oocytes. The results suggest that SCD1 activity is required for cumulus cell lipid storage and steroidogenesis. In addition, oocyte maturation is negatively affected by SCD1 inhibition in cumulus cells, possibly due to a deficient lipid-mediated paracrine support.