RESUMO
Phospholipids containing a single polyunsaturated fatty acyl tail (PL-PUFA1s) are considered the driving force behind ferroptosis, whereas phospholipids with diacyl-PUFA tails (PL-PUFA2s) have been rarely characterized. Dietary lipids modulate ferroptosis, but the mechanisms governing lipid metabolism and ferroptosis sensitivity are not well understood. Our research revealed a significant accumulation of diacyl-PUFA phosphatidylcholines (PC-PUFA2s) following fatty acid or phospholipid treatments, correlating with cancer cell sensitivity to ferroptosis. Depletion of PC-PUFA2s occurred in aging and Huntington's disease brain tissue, linking it to ferroptosis. Notably, PC-PUFA2s interacted with the mitochondrial electron transport chain, generating reactive oxygen species (ROS) for initiating lipid peroxidation. Mitochondria-targeted antioxidants protected cells from PC-PUFA2-induced mitochondrial ROS (mtROS), lipid peroxidation, and cell death. These findings reveal a critical role for PC-PUFA2s in controlling mitochondria homeostasis and ferroptosis in various contexts and explain the ferroptosis-modulating mechanisms of free fatty acids. PC-PUFA2s may serve as diagnostic and therapeutic targets for modulating ferroptosis.
Assuntos
Gorduras na Dieta , Ferroptose , Fosfolipídeos , Ácidos Graxos , Fosfatidilcolinas , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Espécies Reativas de Oxigênio , Gorduras na Dieta/metabolismoRESUMO
One-fourth of all deaths in industrialized countries result from coronary heart disease. A century of research has revealed the essential causative agent: cholesterol-carrying low-density lipoprotein (LDL). LDL is controlled by specific receptors (LDLRs) in liver that remove it from blood. Mutations that eliminate LDLRs raise LDL and cause heart attacks in childhood, whereas mutations that raise LDLRs reduce LDL and diminish heart attacks. If we are to eliminate coronary disease, lowering LDL should be the primary goal. Effective means to achieve this goal are currently available. The key questions are: who to treat, when to treat, and how long to treat.
Assuntos
Colesterol/metabolismo , Vasos Coronários/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Placa Aterosclerótica/tratamento farmacológico , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Vasos Coronários/metabolismo , Gorduras na Dieta/metabolismo , Humanos , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Receptores de LDL/metabolismoRESUMO
Digested dietary fats are taken up by enterocytes where they are assembled into pre-chylomicrons in the endoplasmic reticulum followed by transport to the Golgi for maturation and subsequent secretion to the circulation1. The role of mitochondria in dietary lipid processing is unclear. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with specific ablation of the mitochondrial aspartyl-tRNA synthetase DARS2 (ref. 2), the respiratory chain subunit SDHA3 or the assembly factor COX10 (ref. 4) in intestinal epithelial cells showed accumulation of large lipid droplets (LDs) in enterocytes of the proximal small intestine and failed to thrive. Feeding a fat-free diet suppressed the build-up of LDs in DARS2-deficient enterocytes, which shows that the accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed an impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in intestinal epithelial cells. DARS2 deficiency caused a distinct lack of mature chylomicrons concomitant with a progressive dispersal of the Golgi apparatus in proximal enterocytes. This finding suggests that mitochondrial dysfunction results in impaired trafficking of chylomicrons from the endoplasmic reticulum to the Golgi, which in turn leads to storage of dietary lipids in large cytoplasmic LDs. Taken together, these results reveal a role for mitochondria in dietary lipid transport in enterocytes, which might be relevant for understanding the intestinal defects observed in patients with mitochondrial disorders5.
Assuntos
Gorduras na Dieta , Enterócitos , Metabolismo dos Lipídeos , Mitocôndrias , Animais , Camundongos , Aspartato-tRNA Ligase/metabolismo , Quilomícrons/metabolismo , Gorduras na Dieta/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Retículo Endoplasmático/metabolismo , Enterócitos/metabolismo , Enterócitos/patologia , Células Epiteliais/metabolismo , Complexo de Golgi/metabolismo , Intestinos , Gotículas Lipídicas/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologiaRESUMO
Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber.
Assuntos
Gluconeogênese , Mucosa Intestinal/metabolismo , Intestinos/inervação , Animais , Encéfalo/metabolismo , Gorduras na Dieta/metabolismo , Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Glucose/metabolismo , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Homeostase , Resistência à Insulina , Camundongos , Microbiota , Obesidade/metabolismo , Oligossacarídeos/metabolismo , RatosRESUMO
The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.
Assuntos
Cromatina/metabolismo , Relógios Circadianos , Ritmo Circadiano , Dieta Hiperlipídica , Gorduras na Dieta/metabolismo , Metabolismo Energético , Fígado/metabolismo , Obesidade/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Glicemia/metabolismo , Relógios Circadianos/genética , Ritmo Circadiano/genética , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/sangue , Modelos Animais de Doenças , Metabolismo Energético/genética , Jejum/metabolismo , Regulação da Expressão Gênica , Glucocorticoides/metabolismo , Gluconeogênese , Ligantes , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/sangue , Obesidade/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Período Pós-Prandial , Receptores de Glucocorticoides/deficiência , Receptores de Glucocorticoides/genética , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Via Secretória , Transdução de Sinais , Fatores de Tempo , Transcrição Gênica , Triglicerídeos/sangueRESUMO
Chronic inflammation is a fundamental aspect of metabolic disorders such as obesity, diabetes and cardiovascular disease. Cholesterol crystals are metabolic signals that trigger sterile inflammation in atherosclerosis, presumably by activating inflammasomes for IL-1ß production. We found here that atherogenesis was mediated by IL-1α and we identified fatty acids as potent inducers of IL-1α-driven vascular inflammation. Fatty acids selectively stimulated the release of IL-1α but not of IL-1ß by uncoupling mitochondrial respiration. Fatty acid-induced mitochondrial uncoupling abrogated IL-1ß secretion, which deviated the cholesterol crystal-elicited response toward selective production of IL-1α. Our findings delineate a previously unknown pathway for vascular immunopathology that links the cellular response to metabolic stress with innate inflammation, and suggest that IL-1α, not IL-1ß, should be targeted in patients with cardiovascular disease.
Assuntos
Aterosclerose/metabolismo , Ácidos Graxos/metabolismo , Inflamassomos/metabolismo , Interleucina-1alfa/metabolismo , Mitocôndrias/metabolismo , Vasculite/metabolismo , Animais , Aterosclerose/genética , Aterosclerose/patologia , Sinalização do Cálcio , Gorduras na Dieta/metabolismo , Ácidos Graxos/farmacologia , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Canais Iônicos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Ácido Oleico/farmacologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Proteína Desacopladora 2 , Vasculite/patologiaRESUMO
Omega-3 fatty acids (omega-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Here, we show that the G protein-coupled receptor 120 (GPR120) functions as an omega-3 FA receptor/sensor. Stimulation of GPR120 with omega-3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages. All of these effects are abrogated by GPR120 knockdown. Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistance in obesity, we fed obese WT and GPR120 knockout mice a high-fat diet with or without omega-3 FA supplementation. The omega-3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional omega-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.
Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Resistência à Insulina , Receptores Acoplados a Proteínas G/metabolismo , Células 3T3-L1 , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Linhagem Celular , Gorduras na Dieta/metabolismo , Suplementos Nutricionais , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/metabolismo , Macrófagos/imunologia , Camundongos , Camundongos Knockout , Obesidade/complicações , Receptores Acoplados a Proteínas G/genéticaRESUMO
BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for â¼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.
Assuntos
Cardiolipinas , Ácido Linoleico , Masculino , Camundongos , Animais , Cardiolipinas/metabolismo , Mitocôndrias , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Fígado/metabolismo , Dieta , Fosfolipídeos/metabolismo , Ácidos Linoleicos/metabolismo , RespiraçãoRESUMO
BACKGROUND: High-fiber diets are supplemented with lipids to meet the required energy content, but data on the interactions between dietary fiber (DF) and lipid types on gastrointestinal fermentation in pigs are scant. OBJECTIVES: This study aimed to use a combination of in vivo and in vitro fermentation methodologies to determine the interactive effects of DF and lipid types on short-chain fatty acid (SCFA) production and absorption and organic matter (OM) fermentability in the cecum and colorectal tract of pigs. METHODS: Eight ileal- and cecal-cannulated Yorkshire barrows were fed either pectin- or cellulose-containing diets that were supplemented with either corn oil or beef tallow in 2 independent Youden squares with a 2 × 2 factorial arrangement of treatments (n = 6). Ileal and cecal digesta were collected, freeze-dried, and fermented using inoculum from fresh cecal digesta and feces, respectively, to determine individual SCFA production and absorption and fermentability of OM. RESULTS: Interactions (P < 0.001) between DF and lipid types were observed in which the addition of beef tallow decreased the quantity of cecal and colorectal acetic acid production and cecal acetic absorption, cecal butyric production, predicted cecal OM fermentability, and predicted colorectal propionic acid in pectin diets, but the effects were not observed for cellulose diets. The addition of beef tallow increased (P < 0.001) the production of cecal butyric and propionic acids during in vitro fermentation in cellulose diets and apparent total tract digestibility (ATTD) of OM in pectin diets. CONCLUSIONS: The interactions between DF and lipids on gastrointestinal fermentation largely depend on the degree of saturation of fatty acids in dietary lipids. The addition of beef tallow selectively decreased the production and absorption of individual SCFAs in pectin and cellulose diets but increased cecal butyric and propionic acid production in cellulose diets and the ATTD of OM in pectin diets.
Assuntos
Ceco , Fibras na Dieta , Ácidos Graxos Voláteis , Fermentação , Animais , Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Ceco/metabolismo , Suínos , Masculino , Colo/metabolismo , Pectinas/metabolismo , Dieta/veterinária , Ração Animal/análise , Gorduras na Dieta/metabolismo , Celulose/metabolismo , Digestão , GordurasRESUMO
The present study investigated the potential role of the composition of dietary fatty acids in the regulation of biological rhythms, such as the sleep architecture, core body temperature and leukocyte clock gene expression, in subjects fed meals rich in palmitic acid (PA) or oleic acid (OA). Eleven males participated in two sessions of indirect calorimetry in a whole-room metabolic chamber. In each session, subjects consumed three meals rich in PA (44·3 % of total fat as PA and 42·3 % as OA) or OA (11·7 % of total fat as PA and 59·3 % as OA) in the metabolic chamber. The ratio of PA to OA in plasma was significantly lower and fat oxidation was significantly higher during 24 h of indirect calorimetry in the session with meals rich in OA than in that with meals rich in PA. The duration of slow wave sleep (SWS) was shorter, the latency of SWS was longer and the nadir of core body temperature after bedtime was later in the session with meals rich in PA than in that with meals rich in OA. The peak in CRY1 gene expression was earlier and its amplitude was higher in the session with meals rich in PA than in that with meals rich in OA. In healthy young males, meals rich in PA decreased fat oxidation and disrupted biological rhythms, particularly the sleep architecture and core body temperature during sleep, more than meals rich in OA.
Assuntos
Ácido Oleico , Ácido Palmítico , Masculino , Humanos , Japão , Metabolismo Energético , Periodicidade , Gorduras na Dieta/metabolismoRESUMO
PURPOSE: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. METHODS: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. RESULTS: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. CONCLUSION: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.
Assuntos
Células Endoteliais , Ácidos Graxos , Adulto , Humanos , Pessoa de Meia-Idade , Células Endoteliais/metabolismo , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados , Dieta , Laticínios , Período Pós-Prandial , Gorduras na Dieta/metabolismo , Estudos Cross-OverRESUMO
PURPOSE: To investigate the associations of overall diet quality and dietary factors with serum biomarkers for lipid and amino acid metabolism in a general population of children. METHODS: We studied 194 girls and 209 boys aged 6-8 years participating in the Physical Activity and Nutrition in Children study. Food consumption was assessed by 4-day food records and diet quality was quantified by the Finnish Children Healthy Eating Index (FCHEI). Fasting serum fatty acids, amino acids, apolipoproteins, as well as lipoprotein particle sizes were analyzed with high-throughput nuclear magnetic resonance spectroscopy. Data were analyzed using linear regression adjusted for age, sex, and body fat percentage. RESULTS: FCHEI was directly associated with the ratio of polyunsaturated (PUFA) to saturated fatty acids (SFA) (PUFA/SFA), the ratio of PUFA to monounsaturated fatty acids (MUFA) (PUFA/MUFA), the ratio of PUFA to total fatty acids (FA) (PUFA%), the ratio of omega-3-fatty acids to total FA (omega-3 FA%), and inversely associated with the ratio of MUFA to total FA (MUFA%), alanine, glycine, histidine and very-low density lipoprotein (VLDL) particle size. Consumption of vegetable oils and vegetable-oil-based margarine (≥ 60% fat) was directly associated with PUFA/SFA, PUFA/MUFA, PUFA%, the ratio of omega-6 FA to total FA (omega-6 FA%), and inversely associated with SFA, MUFA, SFA to total FA (SFA%), MUFA%, alanine and VLDL particle size. Consumption of high-fiber grain products directly associated with PUFA/SFA, PUFA/MUFA, omega-3 FA%, omega-6 FA%, PUFA% and inversely associated with SFA and SFA%. Fish consumption directly related to omega-3 FA and omega-3 FA%. Consumption of sugary products was directly associated with histidine and VLDL particle size. Vegetable, fruit, and berry consumption had direct associations with VLDL particle size and the ratio of apolipoprotein B to apolipoprotein A1. Consumption of low fat (< 1%) milk was directly associated with phenylalanine. A higher consumption of high-fat (≥ 1%) milk was associated with lower serum MUFA/SFA and higher SFA%. Sausage consumption was directly related to SFA% and histidine. Red meat consumption was inversely associated with glycine. CONCLUSIONS: Better diet quality, higher in intake of dietary sources of unsaturated fat and fiber, and lower in sugary product intake were associated with more favorable levels of serum biomarkers for lipid and amino acid metabolism independent of adiposity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776, registered March 3, 2013.
Assuntos
Gorduras na Dieta , Ácidos Graxos Ômega-3 , Masculino , Feminino , Animais , Criança , Humanos , Gorduras na Dieta/metabolismo , Finlândia , Histidina , Ácidos Graxos Insaturados , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados , Dieta com Restrição de Gorduras , Biomarcadores , Alanina , GlicinaRESUMO
BACKGROUND: Numerous studies have revealed the role of dietary fatty acids in human health. However, few studies have evaluated dietary fatty acid patterns and their association with metabolic parameters. The current study aimed to explore the association between dietary fatty acid patterns and risk factors for metabolic syndrome (MetS) among overweight and obese adults. METHODS: This cross-sectional study involved 340 participants who were overweight or obese. The study included assessments of body composition and anthropometric measurements. Dietary fatty acid consumption was evaluated using a validated Food Frequency Questionnaire (FFQ) containing 168 items. Additionally, biochemical parameters, including serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting serum glucose (FSG), and insulin levels, were measured using enzymatic methods. Fatty acid patterns were determined by principal component analysis (PCA), and the association between these dietary FA patterns and risk factors related to MetS components was assessed using logistic regression. RESULTS: Factor analysis conducted in this study explored three dietary fatty acid patterns: saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), and long-chain combined fatty acids (LC-CFA). Those at the highest tertile of the SFA pattern had lower diastolic blood pressure (DBP) (P = 0.03). Low-density lipoprotein cholesterol (LDL) was lower in the second and third tertiles (P ≤ 0.05). Also, higher fasting blood glucose (FBS) was observed in the second and third tertiles (P < 0.05), and the homeostatic model assessment of insulin resistance (HOMA-IR) was higher in the third tertile (P = 0.049). In the PUFA pattern, FBS was lower in the third tertile (P = 0.03). In the LC-CFA pattern, lower TC was achieved in higher tertiles (P = 0.04). CONCLUSION: Our findings demonstrated that consuming high and moderate SFA patterns is associated with higher FBS and HOMA-IR. Also, increased consumption of SCFAs is related to lower DPB and LDL. Individuals who consumed more PUFA, especially linoleic acid, had lower FBS. These outcomes might be beneficial in managing MetS and leading to a new field of research.
Assuntos
Gorduras na Dieta , Ácidos Graxos , Síndrome Metabólica , Obesidade , Sobrepeso , Humanos , Masculino , Feminino , Estudos Transversais , Adulto , Obesidade/metabolismo , Sobrepeso/metabolismo , Pessoa de Meia-Idade , Ácidos Graxos/metabolismo , Síndrome Metabólica/metabolismo , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Gorduras na Dieta/metabolismo , Fatores de Risco , Metaboloma , Biomarcadores/sangue , Biomarcadores/análiseRESUMO
Diet shifts can alter tissue fatty acid composition in birds, which is subsequently related to metabolic patterns. Eicosanoids, short-lived fatty acid-derived hormones, have been proposed to mediate these relationships but neither baseline concentrations nor the responses to diet and exercise have been measured in songbirds. We quantified a stable derivative of the vasodilatory eicosanoid prostacyclin in the plasma of male European Starlings (Sturnus vulgaris, N = 25) fed semisynthetic diets with either high (PUFA) or low (MUFA) amounts of n6 fatty acid precursors to prostacyclin. Plasma samples were taken from each bird before, immediately after, and two days following a 15-day flight-training regimen that a subset of birds (N = 17) underwent. We found elevated prostacyclin levels in flight-trained birds fed the PUFA diet compared to those fed the MUFA diet and a positive relationship between prostacyclin and body condition, indexed by fat score. Prostacyclin concentrations also significantly decreased at the final time point. These results are consistent with the proposed influences of precursor availability (i.e., dietary fatty acids) and regulatory feedback associated with exercise (i.e., fuel supply and inflammation), and suggest that prostacyclin may be an important mediator of dietary influence on songbird physiology.
Assuntos
Epoprostenol , Aves Canoras , Masculino , Animais , Aves Canoras/metabolismo , Ácidos Graxos , Eicosanoides , Hormônios , Gorduras na Dieta/metabolismoRESUMO
In mammals, physiological processes related to lipid metabolism, such as chylomicron synthesis or fatty acid oxidation (FAO), modulate eating, highlighting the importance of energostatic mechanisms in feeding control. This study, using rainbow trout (Oncorhynchus mykiss) as model, aimed to characterize the role of FAO and chylomicron formation as peripheral lipid sensors potentially able to modulate feeding in fish. Fish fed with either a normal- (24%) or high- (32%) fat diet were intraperitoneally injected with water alone or containing etomoxir (inhibitor of FAO rate-limiting enzyme carnitine palmitoyl-transferase 1). First, feed intake levels were recorded. We observed an etomoxir-derived decrease in feeding at short times, but a significant increase at 48 h after treatment in fish fed normal-fat diet. Then, we evaluated putative etomoxir effects on the mRNA abundance of genes related to lipid metabolism, chylomicron synthesis and appetite-regulating peptides. Etomoxir treatment upregulated mRNA levels of genes related to chylomicron assembly in proximal intestine, while opposite effects occurred in distal intestine, indicating a clear regionalization in response. Etomoxir also modulated gastrointestinal hormone mRNAs in proximal intestine, upregulating ghrl in fish fed normal-fat diet and pyy and gcg in fish fed high-fat diet. These results provide evidence for an energostatic control of feeding related to FAO and chylomicron formation at the peripheral level in fish.
Assuntos
Quilomícrons , Gorduras na Dieta , Ácidos Graxos , Metabolismo dos Lipídeos , Oncorhynchus mykiss , Oxirredução , Animais , Oncorhynchus mykiss/metabolismo , Ácidos Graxos/metabolismo , Quilomícrons/metabolismo , Gorduras na Dieta/metabolismo , Gorduras na Dieta/farmacologia , Trato Gastrointestinal/metabolismo , Compostos de Epóxi/metabolismo , Compostos de Epóxi/farmacologia , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genéticaRESUMO
1. An experiment was conducted to determine the effect of the source of fat (soybean oil or tallow) on the ileal endogenous amino acid (EAA) losses in broilers.2. Three nitrogen (N)-free diets; a control diet with no added fat and test diets with 60 g/kg of either soybean oil or tallow were formulated. Titanium dioxide (5 g/kg) was added to all diets as an indigestible marker. Each diet was assigned to six replicate cages (eight birds per cage) from d 18 to 21 post-hatch. On d 21, the digesta were collected from the lower half of the ileum.3. The endogenous losses of nitrogen and amino acids (AA) were lower (p = 0.08; p = 0.001) in broilers fed diets with soybean oil or tallow, respectively, compared to those fed the diet with no fat. Source of fat had no influence (p > 0.05) on EAA losses.4. The most abundant AA in the ileal endogenous protein was glutamic acid, followed by aspartic acid, threonine, leucine, serine, valine and proline. In general, the concentrations of AA in the endogenous protein were lower (p < 0.05) with added fat. The exceptions were methionine, cysteine, proline and serine, which were unaffected. The effect of fat source on the AA contents of endogenous protein were inconsistent and differed depending on the AA.5. The inclusion of fats decreased EAA losses which implied they have beneficial effects beyond direct energy contribution. It can be proposed that the reduction of EAA flow may be an additional mechanism contributing to the extra-caloric effect of dietary fats.
Assuntos
Aminoácidos , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Galinhas , Dieta , Gorduras na Dieta , Íleo , Óleo de Soja , Animais , Galinhas/fisiologia , Galinhas/metabolismo , Aminoácidos/metabolismo , Íleo/metabolismo , Ração Animal/análise , Óleo de Soja/administração & dosagem , Óleo de Soja/metabolismo , Dieta/veterinária , Gorduras na Dieta/metabolismo , Gorduras na Dieta/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Masculino , Gorduras/metabolismo , Distribuição AleatóriaRESUMO
It is known that dietary factors within the gestational and nursing period affect early life and stably affect later life traits in animals. However, there is very little understanding of whether dietary factors within the early life period from post-nursing to adulthood affect traits in adulthood. To address this, we conducted studies on male C57Bl/6J mice fed from 3 weeks (immediately post-nursing) until 12 weeks (full maturity) using nine different diets varying in all three major macronutrients to parse out the effects of individual macronutrients. Early life macronutrient balance affected body composition and glucose homeostasis in early adulthood, with dietary protein and fat showing major effects. Despite this, mice showed rapid reversal of the effects on body composition and glucose homeostasis of early life diet feeding, upon standard diet feeding in adulthood. However, some traits were persistent, with early life low dietary protein levels stably affecting lean and muscle mass, and early life dietary fat levels stably affecting serum and liver triglyceride levels. In summary, macronutrient balance in the post-nursing early life period does not stably affect adiposity or glucose homeostasis but does impact muscle mass and lipid homeostasis in adulthood, with prominent effects of both protein and fat levels. KEY POINTS: Early life dietary low protein and high fat levels lowered and heightened body mass, respectively. These effects did not substantially persist into adulthood with rapid catch-up growth on a normal diet. Early life protein (negative) and fat (positive) levels affected fat mass. Early life low protein levels negatively affected lean mass. Low protein effects on lower lean and muscle mass persisted into adulthood. Early life macronutrient balance effects did not affect later life glucose homeostasis but early life high fat level affected later life dyslipidaemia. Effects of dietary carbohydrate levels in early and later life were minor.
Assuntos
Gorduras na Dieta , Nutrientes , Camundongos , Masculino , Animais , Gorduras na Dieta/metabolismo , Gorduras na Dieta/farmacologia , Dieta com Restrição de Proteínas , Proteínas Alimentares , Glucose/metabolismo , BiometriaRESUMO
An attraction for palatable foods rich in lipids is shared by rodents and humans. Over the last decade, the mechanisms responsible for this specific eating behavior have been actively studied, and compelling evidence implicates a taste component in the orosensory detection of dietary lipids [i.e., long-chain fatty acids (LCFA)], in addition to textural, olfactory, and postingestive cues. The interactions between LCFA and specific receptors in taste bud cells (TBC) elicit physiological changes that affect both food intake and digestive functions. After a short overview of the gustatory pathway, this review brings together the key findings consistent with the existence of a sixth taste modality devoted to the perception of lipids. The main steps leading to this new paradigm (i.e., chemoreception of LCFA in TBC, cell signaling cascade, transfer of lipid signals throughout the gustatory nervous pathway, and their physiological consequences) will be critically analyzed. The limitations to this concept will also be discussed in the light of our current knowledge of the sense of taste. Finally, we will analyze the recent literature on obesity-related dysfunctions in the orosensory detection of lipids ("fatty" taste?), in relation to the overconsumption of fat-rich foods and the associated health risks.
Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Comportamento Alimentar , Preferências Alimentares , Obesidade/etiologia , Percepção Gustatória , Paladar , Animais , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Humanos , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/psicologia , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Risco , Transdução de Sinais , Papilas Gustativas/metabolismoRESUMO
PURPOSE OF REVIEW: Given the world-wide problem of obesity, this review considers what types of dietary changes can be utilized to minimize the adverse effects of an obesogenic diet on the intestinal microbiota. RECENT FINDINGS: In rodents fed high-fat diets containing lard or Western blend fats to induce obesity, switching to high-fat diets formulated to contain higher amounts of fiber or fiber-containing foods, plant extracts, omega-3 fatty acids or whole grains has beneficial effects on body weight, metabolic alterations, and the intestinal microbiota. Several studies show that the intestinal microbiota has a role in mediating the beneficial health effects of these dietary factors. Many aspects of the microbiota observed in animals when healthful dietary components were added to the feed have also been observed in humans who follow healthful dietary patterns. SUMMARY: The data shows that specific foods and macronutrients can normalize the obesity-associated microbiota and improve metabolic health. These findings support the design of dietary interventions that would allow individuals to focus on diet quality independently of weight loss to mitigate the adverse sequelae of obesity.
Assuntos
Dieta Hiperlipídica , Disbiose , Animais , Humanos , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/metabolismo , Obesidade/metabolismo , Peso Corporal , Tecido Adiposo/metabolismoRESUMO
The present study aimed to reveal the role of inositol-requiring enzyme 1α (Ire1α) in mediating high-fat-diet (HFD) induced inflammation and apoptosis in fish and elucidate underling mechanisms of action. In experiment 1, black seabream juveniles were fed a control diet (Control, 12 % dietary lipid) or a high fat diet (HFD, 19 % dietary lipid) for eight weeks. In experiment 2, primary hepatocytes were isolated from black seabream juveniles and treated with oleic acid (OA, 200 µmol/L), OA + transfection with non-silencing control siRNA (negative control) (OA + NC), and OA + transfection with ire1α-small interfering RNA (OA + siire1α) for 48 h versus untreated (Control). Results indicated that fish fed HFD increased lipid deposition in the liver and caused hepatic steatosis. HFD group had significantly higher ire1α/Ire1α mRNA and phosphorylated protein expression and endoplasmic reticulum stress (ERS) related genes expression compared to the Control group, indicating that ERS was triggered. Meanwhile, feeding HFD induced inflammation and apoptosis by evaluated nuclear factor kappa B (nf-κb) mRNA and phosphorylated Nf-κb p65 protein expression, and c-Jun N-terminal kinase (jnk) mRNA and protein expression. However, knock down of ire1α (OA + siire1α) in primary hepatocytes alleviated OA-induced increased expression of ire1α/Ire1α mRNA and protein expression, nf-κb/Nf-κb p65 mRNA and phosphorylated protein expression, and jnk/Jnk mRNA and phosphorylated protein expression. These findings revealed the underling mechanism of action of HFD in fish, confirming that HFD increased ESR stress and Ire1α that, in turn, activated Nf-κb and Jnk pathways in hepatocytes and liver mediating HFD-induced inflammation and apoptosis.