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Free Fatty Acids Signature in Human Intestinal Disorders: Significant Association between Butyric Acid and Celiac Disease.
Baldi, S, Menicatti, M, Nannini, G, Niccolai, E, Russo, E, Ricci, F, Pallecchi, M, Romano, F, Pedone, M, Poli, G, et al
Nutrients. 2021;(3)
Abstract
Altered circulating levels of free fatty acids (FFAs), namely short chain fatty acids (SCFAs), medium chain fatty acids (MCFAs), and long chain fatty acids (LCFAs), are associated with metabolic, gastrointestinal, and malignant diseases. Hence, we compared the serum FFA profile of patients with celiac disease (CD), adenomatous polyposis (AP), and colorectal cancer (CRC) to healthy controls (HC). We enrolled 44 patients (19 CRC, 9 AP, 16 CD) and 16 HC. We performed a quantitative FFA evaluation with the gas chromatography-mass spectrometry method (GC-MS), and we performed Dirichlet-multinomial regression in order to highlight disease-specific FFA signature. HC showed a different composition of FFAs than CRC, AP, and CD patients. Furthermore, the partial least squares discriminant analysis (PLS-DA) confirmed perfect overlap between the CRC and AP patients and separation of HC from the diseased groups. The Dirichlet-multinomial regression identified only strong positive association between CD and butyric acid. Moreover, CD patients showed significant interactions with age, BMI, and gender. In addition, among patients with the same age and BMI, being male compared to being female implies a decrease of the CD effect on the (log) prevalence of butyric acid in FFA composition. Our data support GC-MS as a suitable method for the concurrent analysis of circulating SCFAs, MCFAs, and LCFAs in different gastrointestinal diseases. Furthermore, and notably, we suggest for the first time that butyric acid could represent a potential biomarker for CD screening.
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Obstructive Sleep Apnea Dynamically Increases Nocturnal Plasma Free Fatty Acids, Glucose, and Cortisol During Sleep.
Chopra, S, Rathore, A, Younas, H, Pham, LV, Gu, C, Beselman, A, Kim, IY, Wolfe, RR, Perin, J, Polotsky, VY, et al
The Journal of clinical endocrinology and metabolism. 2017;(9):3172-3181
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Abstract
CONTEXT Obstructive sleep apnea (OSA) is associated with diabetes and cardiovascular disease. This association may be related to metabolic changes that transpire during sleep in OSA. OBJECTIVE To examine the impact of OSA, elicited by cessation of continuous positive airway pressure (CPAP), on frequently sampled nocturnal metabolic markers including plasma free fatty acids (FFAs), glucose, insulin, triglycerides (TGs), cortisol, and lactate, as well as glucose production, oral glucose tolerance, blood pressure (BP), endothelial function, cholesterol, and high-sensitivity C-reactive protein (hsCRP). DESIGN AND SETTING Randomized crossover trial of CPAP vs CPAP withdrawal. PATIENTS Thirty-one patients with moderate to severe OSA acclimated to CPAP. INTERVENTION Patients underwent attended polysomnography while sleeping with therapeutic CPAP, or after CPAP withdrawal, in random order. Venous blood was sampled at ∼20-minute intervals on both nights. In 11 patients, we assessed glucose kinetics with an infusion of 6,6-[2H2]glucose. RESULTS CPAP withdrawal caused recurrence of OSA associated with hypoxemia, sleep disruption, and heart rate (HR) elevation. CPAP withdrawal dynamically increased nocturnal FFA (P = 0.007), glucose (P = 0.028), and cortisol (P = 0.037), in proportion to respiratory event frequency, HR elevation, or sleep fragmentation. Diabetes predisposed to glucose elevation. CPAP withdrawal also increased systolic BP (P = 0.017) and augmentation index (P = 0.008), but did not affect insulin, TGs, glucose production, oral glucose tolerance, cholesterol, or hsCRP. CONCLUSION OSA recurrence during CPAP withdrawal increases FFA and glucose during sleep, associated with sympathetic and adrenocortical activation. Recurring exposure to these metabolic changes may foster diabetes and cardiovascular disease.
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The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy.
Masquio, DC, de Piano-Ganen, A, Oyama, LM, Campos, RM, Santamarina, AB, de Souza, GI, Gomes, AD, Moreira, RG, Corgosinho, FC, do Nascimento, CM, et al
The Journal of nutritional biochemistry. 2016;:136-44
Abstract
The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum fatty acids can be influenced by lifestyle changes and are able to modulate these biomarkers.
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The influence of glucose load on metabolism during minor surgery using remifentanil-induced anesthesia.
Kambe, N, Tanaka, K, Kakuta, N, Kawanishi, R, Tsutsumi, YM
Acta anaesthesiologica Scandinavica. 2014;(8):948-54
Abstract
BACKGROUND During perioperative fasting, lipid metabolism gradually increases, resulting in free fatty acids (FFA) and/or ketone bodies. Suppression of surgical stress by remifentanil may allow the safe administration of glucose infusions, avoiding both hyperglycemia and ketogenesis. The effects of glucose infusion on glucose and lipid metabolism were therefore investigated in patients undergoing minor surgery with remifentanil anesthesia. METHODS Thirty-four patients were randomized 1 : 1 to receive no glucose (0G group) or low-dose glucose (0.1 g/kg/h for 1 h followed by 0.05 g/kg/h for 1 h; LG group). The concentrations of glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, FFA, creatinine (Cr), and ketone bodies were measured before anesthetic induction, 1 and 2 h after glucose infusion, at the end of surgery, and the next morning. RESULTS The concentrations of cortisol and ACTH decreased during surgery in both groups when compared with the concentrations before anesthesia and at the end of surgery (P < 0.05). Glucose and insulin concentrations were significantly higher in the LG than in the 0G group at 1 and 2 h after infusion. No patient experienced hyperglycemia. The concentrations of FFA and ketone bodies were lower in the LG than in the 0G group during surgery, but there were no significant between group differences in 3-MH/Cr. CONCLUSION Infusion of low-dose glucose attenuated fat catabolism without causing hyperglycemia, indicating that infusion of low-dose glucose during remifentanil-induced anesthesia may be safe for patients.
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Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women.
Törrönen, R, Kolehmainen, M, Sarkkinen, E, Mykkänen, H, Niskanen, L
The American journal of clinical nutrition. 2012;(3):527-33
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BACKGROUND Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.
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Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects.
Holmer-Jensen, J, Hartvigsen, ML, Mortensen, LS, Astrup, A, de Vrese, M, Holst, JJ, Thomsen, C, Hermansen, K
European journal of clinical nutrition. 2012;(1):32-8
Abstract
BACKGROUND/OBJECTIVES Postprandial lipaemia is an established risk factor for atherosclerosis. To investigate the acute effect of four milk-derived dietary proteins (alpha-lactalbumin, whey isolate, caseinoglycomacropeptide and whey hydrolysate) on postprandial lipaemia, we have conducted a randomized, acute, single-blinded clinical intervention study with crossover design. SUBJECTS/METHODS A total of 11 obese non-diabetic subjects (age: 44-74, BMI: 30-41.4 kg m(-2)) were included. On 4 different days the subjects ingested a high-fat meal with the following energy distribution: 66% energy from fat (100 g of butter), 15% of energy from carbohydrate (90 g of white wheat bread) and 19% of energy from protein (45 g of pure protein). Our primary variable was plasma triglyceride measured in the 8-h postprandial period. Secondarily, retinyl palmitate, non-esterified free fatty acids, glucose, insulin, glucagon, GLP-1 and GIP, active and total grehlin and cholecystokinin were measured. RESULTS We observed no statistically significant (P=0.8) differences between meals on our primary variable that is, triglycerides. Whey hydrolysate was associated with a significantly (P=0.02) smaller postprandial suppression of non-esterified free fatty acids compared with the other dietary proteins. CONCLUSION We did not observe significant differences in postprandial lipaemia to the four milk-derived dietary proteins. Whey hydrolysate caused less postprandial suppression of free fatty acids.
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Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men.
Marinou, K, Adiels, M, Hodson, L, Frayn, KN, Karpe, F, Fielding, BA
The British journal of nutrition. 2011;(6):857-65
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Abstract
Before the menopause, women are relatively protected against CVD compared with men. The reasons for this sex difference are not completely understood, but hepatic fatty acid metabolism may play a role. The present study aimed to investigate the utilisation of plasma NEFA by the liver and to determine whether they are partitioned differently into ketone bodies and VLDL-TAG in healthy, lean young men and women. Volunteers were studied during a prolonged overnight fast (12-19 h) using an intravenous infusion of [U-¹³C]palmitate. After 12 h fasting, the women had a more advantageous metabolic profile with lower plasma glucose (P < 0·05) and TAG (P < 0·05) but higher plasma NEFA (P < 0·05) concentrations. Plasma 3-hydroxybutyrate (3-OHB) concentrations rose more in women than in men, and the transfer of ¹³C from [U-¹³C]palmitate to plasma [¹³C]3-OHB reached a plateau 6-7 h after the start of the infusion in women but was still increasing at 6 h in men. This implies a slower 3-OHB production rate and/or dilution by other precursor pools in men. In women, the high isotopic enrichment of plasma 3-OHB suggested that systemic plasma fatty acids were the major source of 3-OHB production. However, in men, this was not observed during the course of the study (P < 0·01). There were no sex differences for the incorporation of ¹³C into VLDL1- or VLDL2-TAG. The ability of young women to partition fatty acids towards ketone body production rather than VLDL-TAG may contribute to their more advantageous metabolic profile compared with young men.
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Acute effects of pharmacological modifications of fatty acid metabolism on human satiety.
Gatta, B, Zuberbuehler, C, Arnold, M, Aubert, R, Langhans, W, Chapelot, D
The British journal of nutrition. 2009;(12):1867-77
Abstract
The role of NEFA in eating behaviour is still poorly known. Our objective was to examine whether etomoxir (ETO), an inhibitor of NEFA oxidation, or ( - )-hydroxycitrate (HCA), an inhibitor of lipogenesis which may indirectly stimulate NEFA oxidation, alters satiety. Post-lunch satiety was measured in eight normal-weight male subjects who were deprived of time cues and received on three occasions either ETO (320 mg), HCA (2 g) or placebo (PLA) in random order. Between lunch and dinner, blood was withdrawn continuously and collected every 10 min for measures of plasma concentrations of glucose, insulin, lactate, TAG, NEFA, beta-hydroxybutyrate (BHB), leptin and ghrelin. Results showed that HCA began to decrease hunger and desire to eat compared to PLA and ETO 210 min after lunch and increased satiety duration compared to PLA by 70 (se 23) min (P < 0.05), but did not modify energy intake at dinner. ETO did not affect any variable of satiety. HCA increased NEFA concentrations during the pre-dinner period, whereas ETO increased and decreased plasma concentrations of NEFA and BHB, respectively. Mean differences in plasma NEFA concentrations between HCA and PLA were predictive of the differences in satiety duration between treatments (r2 0.71, P < 0.01). Among treatments, plasma leptin concentration at dinner onset was the only blood variable correlated with energy intake at this meal (r - 0.75, P < 0.0005). In healthy, normal-weight men, acute HCA increased the intensity and duration of satiety possibly via increased NEFA disposal for oxidation.
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Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome.
Rosenson, RS
American heart journal. 2008;(3):499.e9-16
Abstract
BACKGROUND Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a macrophage-synthesized lipase that is primarily bound to small electronegative low-density lipoproteins (LDLs). Lipoprotein-associated phospholipase A2 oxidatively modifies LDL and generates the proinflammatory byproducts oxidized fatty acids (ox-FAs) and lysophosphatidylcholine. Fenofibrate reduces Lp-PLA2 mass; however, it remains unknown whether the anti-inflammatory effects of fenofibrate are related to changes in LDL subclasses. METHODS This was a randomized, double-blind, controlled clinical trial designed to investigate the effects of 3-month treatment with fenofibrate (160 mg/d) on Lp-PLA2 mass, LDL subclasses, and ox-FAs among 55 hypertriglyceridemic (> or = 1.7 and < 6.78 mmol/L) subjects with the metabolic syndrome. RESULTS Fenofibrate treatment lowered fasting Lp-PLA2 mass by 13.2% (-19.0 to -7.7) versus placebo (2.3% [-5.0 to 4.1], P = .0002) and total ox-FA by 15.5% (-34.2 to +1.4) versus an 11.5% increase with placebo (P = .0013). In age-, sex-, and treatment-adjusted models, changes in Lp-PLA2 mass were associated with reductions in chemical LDL cholesterol (r = 0.59, P < .01) and measured total LDL particles (LDL-Ps) (r = 0.64, P < .01) and small LDL-Ps (r = 0.57, P < .01). In models that included small LDL, effects of fenofibrate on Lp-PLA2 mass were attenuated (P = .125), but not in models that included LDL cholesterol (P < .0001) and LDL-Ps (P = .005). Changes in Lp-PLA2 mass were not significantly associated with changes in ox-FA or inflammatory markers. CONCLUSIONS Among hypertriglyceridemic subjects with the metabolic syndrome, fenofibrate therapy reduced Lp-PLA2 mass, and these changes were associated with fewer small LDL-Ps.
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Free fatty acids increase hepatic glycogen content in obese males.
Allick, G, Sprangers, F, Weverling, GJ, Ackermans, MT, Meijer, AJ, Romijn, JA, Endert, E, Bisschop, PH, Sauerwein, HP
Metabolism: clinical and experimental. 2004;(7):886-93
Abstract
Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose pathways in lean and obese subjects. Six lean and 6 obese males were studied twice during a 16- to 22-hour fast, once with and once without acipimox, an inhibitor of lipolysis. Intrahepatic glucose fluxes were measured by infusion of [2-(13C1)]glycerol, [1-(2H1)]galactose, and [U-(13C6)]glucose. Acetaminophen was administered as a glucuronate probe. In both lean and obese control studies, plasma FFA levels increased progressively, whereas acipimox completely suppressed plasma FFA levels for the whole study period. In lean males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). In lean males, neither glycogen synthesis, glycogen synthesis retained as glycogen, nor glycogen balance differed between control and acipimox studies. In obese males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). Glycogen synthesis did not change in either study. Glycogen synthesis retained as glycogen did not change in acipimox study, but increased in the control study (P = .03). Glycogen balance did not change in the acipimox study, but increased in the control study (P < .01). This study demonstrates that in obese males physiological levels of FFA contribute to the retention of hepatic glycogen during short-term fasting by inhibiting breakdown of glycogen and increasing glycogen synthesis retained as glycogen, whereas in lean males this effect was absent due to unaltered glycogen synthesis retained as glycogen.