Increase In Free Fatty Acid Levels Research Articles

Maternal high fat diets: impacts on offspring obesity and epigenetic hypothalamic programming.

Maternal high-fat diet (HFD) during pregnancy is associated with rapid weight gain and fetal fat mass increase at an early stage. Also, HFD during pregnancy can cause the activation of proinflammatory cytokines. Maternal insulin resistance and inflammation lead to increased adipose tissue lipolysis, and also increased free fatty acid (FFA) intake during pregnancy (˃35% of energy from fat) cause a significant increase in FFA levels in the fetus. However, both maternal insulin resistance and HFD have detrimental effects on adiposity in early life. As a result of these metabolic alterations, excess fetal lipid exposure may affect fetal growth and development. On the other hand, increase in blood lipids and inflammation can adversely affect the development of the liver, adipose tissue, brain, skeletal muscle, and pancreas in the fetus, increasing the risk for metabolic disorders. In addition, maternal HFD is associated with changes in the hypothalamic regulation of body weight and energy homeostasis by altering the expression of the leptin receptor, POMC, and neuropeptide Y in the offspring, as well as altering methylation and gene expression of dopamine and opioid-related genes which cause changes in eating behavior. All these maternal metabolic and epigenetic changes may contribute to the childhood obesity epidemic through fetal metabolic programming. Dietary interventions, such as limiting dietary fat intake <35% with appropriate fatty acid intake during the gestation period are the most effective type of intervention to improve the maternal metabolic environment during pregnancy. Appropriate nutritional intake during pregnancy should be the principal goal in reducing the risks of obesity and metabolic disorders.

Association between serum free fatty acid levels and tophus in patients with gout: a cross-sectional study.

To explore the relationship between serum free fatty acid (FFA) and tophus in gout patients, and to investigate whether FFA increases the risk of tophus deposition by lowering urine pH. A total of 595 patients with gout aged 18 to 80 were enrolled between June 2018 and August 2021. The subjects were divided into four groups according to FFA. Logistic regression was used to analyse the association between serum FFA and tophus. Receiver operating curves (ROC) were plotted to explore the predictive value of FFA on the occurrence of tophus. Accompanying the increase of FFA levels, the prevalence of tophus in groups Q3 and Q4 was significantly higher than in groups Q1 and Q2 (33.6%, 36.5% vs. 6.3%, 19.6%, p<0.001). According to the Spearman correlation, serum FFA levels were positively correlated with tophus while negatively with urine pH (p<0.001). FFA had a significant interaction with urine pH on tophus risk. Multivariate logistic regression showed that participants in Q2-Q4 had a higher OR of tophus than those in Q1 (OR were 2.770, 5.878 and 7.958 in Q2-Q4, respectively). ROC showed the best cut-off value of serum FFA level in predicting the onset of tophus was 0.46 mmol/L. Serum FFA had a great discriminant ability to predict tophus. High FFA levels are independently associated with tophus risk and FFA may promote tophi deposition by lowering urine pH. Serum FFA levels have a great screening value to identify tophus.

Ingestion of High-Oleic Peanut Improves Endurance Performance in Healthy Individuals

This study aimed at evaluating whether high-oleic peanuts (with skin), which are rich in oleic acid, could serve as an energy substrate for prolonged exercise and improve endurance performance. We evaluated changes in blood biomarker (triglycerides, free fatty acid (FFA), biological antioxidant potential (BAP), malondialdehyde-modified low-density lipoprotein (MDA-LDL), and serum total protein) levels at 2-h intervals for 6 h after the ingestion of 10 g and 30 g of peanuts. The results were used to determine the timing of peanut ingestion before the endurance performance test. As a result, there was a significant change in the 30-g peanut-ingested condition, and lipid levels increased 2 h after the ingestion of 30 g of peanuts. Accordingly, the endurance performance test was conducted 2 h after ingesting 30 g of peanuts. The endurance performance test involved 70 min of pedaling exercise. We measured pre- and postexercise levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a biomarker of oxidative stress. There was a significantly improved workload in the endurance performance test in the high-oleic peanut-ingested condition than in the control condition. Furthermore, the rate of increase in 8-OHdG was significantly lower in the high-oleic peanut-ingested condition than in the control condition. This suggests that the increase in FFA levels resulting from the ingestion of high-oleic peanuts and the inherent antioxidant effects of peanuts improved the workload during endurance exercise.

Heparin Effects on Serum Gonadotropins.

IntroductionStudies using lipid infusions to raise fatty acid levels require heparin to release lipoprotein lipase (LPL), thus calling into question the appropriate control infusion for this type of study: saline alone or saline plus heparin. We aimed to evaluate whether the addition of heparin alone, in doses needed to release LPL, would alter circulating free fatty acids (FFAs) and/or affect gonadotropins.Materials and MethodsThis was a secondary analysis using combined data from eumenorrheic normal-weight women subjected to “control” conditions in 1 of 2 separate studies. In 1 study, participants received saline alone (group 1) as a control, and in the other study participants received saline alone and/or saline plus heparin (groups 2-3) as a control. Both studies performed early follicular phase, frequent blood sampling. FSH and LH were compared across groups and in conditions with and without heparin. Linear mixed models were used to analyze the data.ResultsLH did not differ across any of the 3 groups. Estimated means (SE) for FSH differed between groups but this difference was marginal (P = .05) after adjusting for anti-Mullerian hormone and unrelated to heparin infusion (group 1: 4.47 IU/L [SE 1.19], group 2: 8.01 IU/L [SE 1.14], group 3: 7.94 IU/L [SE 1.13]).ConclusionsHeparin does not exert major effects on gonadotropins when infused in quantities sufficient to release LPL. However, because it can release other vascular membrane-bound proteins, heparin should be considered part of the control infusions in lipid infusion studies where increased FFA levels are the goal.

Analyses of metabolic activity in peanuts under hermetic storage at different relative humidity levels

Peanuts are transported by ship from production regions to all across the globe. Quality problems are frequently encountered due to increased levels of free fatty acids (FFAs) and a decline in organoleptic quality through lipid oxidation occurring during transport and storage. We studied the role of moisture (water activity, aw) in interaction with 87 days hermetic storage under air or nitrogen gas. Upon storage with air, some lipid oxidation was observed at water activity levels below 0.73. FFA levels increased at water activity levels above 0.73 and fungi proliferated at water activities above 0.80. Lipid oxidation, an increase in FFA levels and fungal growth were not observed after storage under nitrogen gas. It can be concluded that peanut storage and transport under anoxia can strongly reduce quality losses.

Mechanism of nonthermal induction of apoptosis by high-intensity focused electromagnetic procedure: Biochemical investigation in a porcine model.

BackgroundMultiple studies have reported adipose tissue reduction after the application of the High‐Intensity Focused Electromagnetic (HIFEM) field technology, yet cellular level evidence of the mechanisms has remained scarce.ObjectivesThis study aims to verify or refute previous single‐study histological evidence and further investigates the proposed mechanism of apoptotic induction.MethodsThe thigh of two Large White pigs was treated with HIFEM for 30 minutes. Fat punch biopsies were collected from the application area before, immediately after, and 8 hours post‐treatment. Control samples were taken from the abdomen immediately after and 8 hours post‐treatment. Samples were analyzed for pro‐apoptotic DNA markers (BAX, BCL‐2, TXNIP, MMP9, TNF‐α), the levels of free fatty acids (FFA), and the pH levels of the adipose tissue.ResultsThe levels of FFA in the treated adipose tissue increased on average by 127.1% immediately post‐treatment and by 134.1% 8 hours post‐treatment, indicating a rapid breakdown of lipids. The average recorded adipose pH changed from 7.30 ± 0.12 at baseline to 6.60 ± 0.07 immediately post‐treatment (P = .001) and to 7.19 ± 0.12 8 hours post‐treatment. The levels of BAX, TXNIP, MMP9, and TNF‐α increased post‐treatment while BCL‐2 decreased. Control samples showed constant levels of pH and pro‐apoptotic markers. The FFAs in the control samples were increased by 41.6%‐51.4%.ConclusionThe changes in the levels of the pro‐apoptotic markers conformed to the previously reported elevated fat apoptosis post‐HIFEM treatments. These effects were accompanied by an increase in FFA levels, and by reduced pH levels, due to the increased acidity in the adipose tissue. Further research is required to explore the potential of nonthermal induction of apoptosis.

Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression.

Autophagy maintains cellular homeostasis by degrading organelles, proteins, and lipids in lysosomes. Autophagy is involved in the innate and adaptive immune responses to a variety of pathogens. Some viruses can hijack host autophagy to enhance their replication. However, the role of autophagy in porcine reproductive and respiratory syndrome virus (PRRSV) infection is unclear. Here, we show that N-Myc downstream-regulated gene 1 (NDRG1) deficiency induced autophagy, which facilitated PRRSV replication by regulating lipid metabolism. NDRG1 mRNA is expressed ubiquitously in most porcine tissues and most strongly in white adipose tissue. PRRSV infection downregulated the expression of NDRG1 mRNA and protein, while NDRG1 deficiency contributed to PRRSV RNA replication and progeny virus assembly. NDRG1 deficiency reduced the number of intracellular lipid droplets (LDs), but the expression levels of key genes in lipogenesis and lipolysis were not altered. Our results also show that NDRG1 deficiency promoted autophagy and increased the subsequent yields of hydrolyzed free fatty acids (FFAs). The reduced LD numbers, increased FFA levels, and enhanced PRRSV replication were abrogated in the presence of an autophagy inhibitor. Overall, our findings suggest that NDRG1 plays a negative role in PRRSV replication by suppressing autophagy and LD degradation.IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-positive-stranded RNA virus, causes acute respiratory distress in piglets and reproductive failure in sows. It has led to tremendous economic losses in the swine industry worldwide since it was first documented in the late 1980s. Vaccination is currently the major strategy used to control the disease. However, conventional vaccines and other strategies do not provide satisfactory or sustainable prevention. Therefore, safe and effective strategies to control PRRSV are urgently required. The significance of our research is that we demonstrate a previously unreported relationship between PRRSV, NDRG1, and lipophagy in the context of viral infection. Furthermore, our data point to a new role for NDRG1 in autophagy and lipid metabolism. Thus, NDRG1 and lipophagy will have significant implications for understanding PRRSV pathogenesis for developing new therapeutics.

Ozone‐Induced Systemic Metabolic Alterations are Regulated by Circulating Stress Hormones in Rats

Several recent studies from our lab and others have demonstrated widespread metabolic effects following an acute ozone exposure. Although these effects are similar to those induced by the fight‐or‐flight response involving adrenal‐derived stress hormones, little data are available linking these metabolic changes to activation of neuroendocrine pathways. In this study, we used surgical and pharmacological interventions to understand the influence of adrenal‐derived stress hormones in mediating ozone‐induced metabolic alterations. Male Wistar‐Kyoto (WKY) rats underwent bilateral total adrenalectomy (ADREX) or sham surgery prior to their exposure to filtered air or ozone (0.8 ppm), 4h/day for 1 day. In the sham animals, ozone exposure induced hyperglycemia and glucose intolerance as well as increased levels of circulating total cholesterol, free fatty acids (FFA), and leptin. ADREX and the resultant depletion of adrenal‐derived stress hormones, adrenaline and corticosterone, significantly attenuated these ozone‐induced metabolic effects. Furthermore, ozone‐induced global transcriptional changes in the liver from sham and ADREX rats were assessed by total mRNA sequencing. The upstream regulator assessment within Ingenuity Pathway Analysis revealed that ozone‐induced changes in gene expression were similar to those induced by corticosterone, methylprednisolone, and forskolin, suggesting glucocorticoids and adrenergic mechanisms significantly contributed to the ozone‐induced changes in the liver. These same regulators were not predicted in the ADREX animals exposed to ozone. In a follow up study, we utilized a non‐specific beta‐adrenergic receptor antagonist (propranolol) and/or glucocorticoid receptor antagonist (mifepristone) to understand the specific contribution of these stress hormones in mediating metabolic effects following ozone exposure. Ozone‐induced hyperglycemia, glucose intolerance, and increased FFA levels were significantly attenuated only by the combination of antagonists, suggesting that both adrenergic and glucocorticoid pathways were involved in the regulation of these processes. However, increases in total cholesterol and leptin levels following ozone exposure were blocked by mifepristone alone and in combination with propranolol, suggesting these ozone effects are glucocorticoid‐dependent. Collectively, these data suggest adrenal‐derived stress hormones play a significant role in mediating ozone‐induced systemic metabolic effects. (Does not reflect the US EPA policy)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Aldosterone stimulation mediates cardiac metabolism remodeling via Sirt1/AMPK signaling in canine model.

Aldosterone (Aldo), a pivotal hormone that is ubiquitously expressed in systemic tissues of mammals, is a crucial factor in the pathogenesis of cardiac disease. Accumulating evidence suggests that disturbances in cell energy metabolism are involved in increasing aldosterone levels. However, the precise mechanism underlying the impact of cardiac metabolic remodeling underlying aldosterone stimulation remains limited. In this work, we evaluated the underlying effect of aldosterone on regulating cardiac metabolism remodeling in a canine model. Fifteen beagle dogs were divided into a control group (n = 5), Aldo group (n = 5), and a group treated with spironolactone (SP), a mineralocorticoid receptor antagonist (n = 5), for 4weeks. Blood pressure, electrocardiogram and respiratory parameters, H&E, Masson staining, ultrastructural changes, the adenosine triphosphate (ATP) and free fatty acid (FFA) levels of ventricular tissues, the level of mRNA, and the protein expression of key metabolic factors and regulators were assessed. The Sirt1/AMPK signaling pathway was significantly inhibited in the canine model of aldosterone stimulation, resulting in a reduction of the key downstream metabolic factors involved in glucose and fatty acid oxidation. The dysregulation of expression of key factors in glycogen metabolism led to glycogen deposition, an increase in FFA levels, a reduction in ATP levels, apoptosis, inflammatory cell infiltration, and mitochondrial damage in the ventricular myocardium. These effects were significantly restored by spironolactone. Aldosterone stimulation induced cardiac metabolic remodeling in ventricular cardiomyocytes possibly through the Sirt1/AMPK signaling pathway, implying that this pathway may provide a novel therapeutic target for cardiac metabolic remodeling.

Acute Effect of Post-Resistance Exercise Milk-Based Supplement on Substrate Oxidation and Fat Mobilization in Older Men: A Pilot Study

Background: It was reported that cow’s milk-based supplementation after resistance training reduced fat mass in older men. The reasons behind this beneficial impact remain to be elucidated. Hence, the aim of this study was to determine the effect of a cow’s milk-based supplementation after resistance exercise on lipid oxidation and systemic fat mobilization in older men. Methods: Older men (age range: 60–75 years) participated in a randomized, double-blind, crossover study with the two following conditions: (1) Resistance exercise + Cow’s milk (C-milk) and (2) Resistance exercise + Rice milk (R-milk; isocaloric control). During a 180-min post-exercise period, energy expenditure, substrate oxidation (indirect calorimetry), plasma levels of glycerol (systemic fat mobilization) and free fatty acids (FFA) were measured. Results: During the 180-min post-exercise period, lipid oxidation remained similar in both conditions. Glycerol levels decreased similarly in C-milk and R-milk (p ≤ 0.045). Although FFA levels increased progressively from 60 min to 180 min post-exercise in both conditions, the magnitude of changes (∆) was greater in C-milk condition between 60 and 120 min post-exercise (p < 0.018). Conclusions: These results do not support a large impact of cow’s milk supplementation after resistance exercise on lipid oxidation and systemic fat mobilization. However, the greater increase in FFA levels suggests that re-esterification may be influenced.

Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart

BackgroundInsulin resistance has been independently related to heart failure. However, the specific mechanisms of high FFA levels in the pathophysiology of heart failure in insulin-resistant states are remain largely unclear. This study investigated whether elevated circulating free fatty acids (FFA) levels result in impaired cardiac structure and function in vivo via insulin-related signaling pathways in myocardium.MethodsMale Wistar rats were randomly divided into the intralipid group (20% intralipid plus heparin infusion) and the control group (glycerol infusion). Blood samples were collected before and after 6-, 12-, and 24-h infusions. Cardiac structure and function were measured using echocardiography. Maximum velocity of myocardial contraction (+dP/dt max) and diastole (−dP/dt max) were measured using a physiological polygraph in vivo. Heart tissues were collected for western blotting.ResultsCompared with the control group, plasma FFA, plasma glucose, and serum insulin levels increased significantly in the intralipid group. With increasing infusion time, cardiac function in the intralipid group decreased gradually compared with the control group. After a 24-h infusion, early (E’, cm/s) diastolic peak velocities and (−dP/dt max) decreased significantly. Protein expression of phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt, and phosphorylated Akt in myocardium increased after a 6-h infusion and decreased significantly after a 24-h infusion in the intralipid group. Protein expression of glucose transporter type 4 (GLUT4), Adenosine 5′-monophosphate -activated protein kinase (AMPK), phosphorylated AMPK(p-AMPK), and endothelial nitric oxide synthase (eNOS) in myocardium gradually decreased in the intralipid group.ConclusionsElevated FFA levels may impair cardiac function and cardiac dysfunction might result from myocardial insulin resistance with significant changes to PI3K-Akt-GLUT4 and AMPK-eNOS signaling pathways with increasing FFA levels.

Shelf Life of Tropical Canarium Nut Stored under Ambient Conditions

There is a need to develop alternative crops to improve the food security and prosperity of developing countries. The tropical nut Canarium indicum (canarium nut) is increasingly used as a shade tree for cocoa and has potential for commercialization as a sustainable crop that will improve food security and livelihoods in Melanesia and East Asia. There is no information on canarium nut shelf life characteristics. Canarium kernels may be prone to rancidity, due to a high content of unsaturated fatty acids. Kernels at 5.4% moisture content were vacuum-packed with a domestic vacuum-packaging system and stored for six months in Papua New Guinea and for nine months in Southeast Queensland, Australia at both ambient temperatures (22 to 31 °C and 22 to 25 °C, respectively) and under refrigeration. Nuts were analysed for changes in peroxide values and free fatty acids (FFAs) over the storage periods that might indicate development of rancidity. Peroxide values indicated very low levels of oxidation in all treatments. Free fatty acids were at low levels but increased significantly during storage at ambient temperatures. The results suggested that vacuum-packed Canarium nuts can be stored safely under ambient tropical conditions for six months with daytime temperatures around 31 °C, and for nine months at 25 °C. Increasing FFA levels at ambient temperatures indicate caution about longer storage time at ambient temperatures. Storage under refrigeration greatly prolonged shelf life.

Impact of Microwave Assisted Infusion on the Quality and Volatile Composition of Olive Oil Aromatized with Rosemary Leaves

AbstractOlive oil with rosemary leaves by microwave assisted infusion (MAI) as an alternative to conventional infusion (CI) was evaluated. Microwave heating was applied to the mixture in order to accelerate diffusion of the rosemary volatile compounds into the olive oil. The volatile components of the aromatized oils were quantified by HS‐SPME/GC–MS, as well as several quality indexes such as free fatty acids (FFA), peroxide value (PV), specific coefficients of extinction, chlorophyll and carotenoid content, and color assessment. Fatty acid profiles of the oils aromatized by MAI were compared to those produced by CI. Results showed that the infusion time is reduced from 12 h to 10 min when utilizing MAI in place of CI. MAI treatment caused a slight increase in FFA levels, and specific extinction coefficient indices (K232 and K270). PV during MAI remained unchanged for the first 3 min, after which there was an observable increase. All physico‐chemical values were found to be well below the maximum permitted limits. The MAI treatment reduced chlorophyll and carotenoid levels during the final step of aromatization, thus affecting final color. The MAI aromatized oil was characterized by its clear green color (L*, a*, b* parameters). Fatty acid analysis showed that MAI slightly changed the fatty acid composition of the olive oil. This study indicates that MAI appears to be a viable and rapid method to flavor olive oil with rosemary leaves.

The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis

Background18F-fluorodeoxyglucose (FDG) PET plays an important role in the detection of cardiac involvement sarcoidosis (CS). However, diffuse left ventricle (LV) wall uptake sometimes makes it difficult to distinguish between positive uptake and physiological uptake. The aims of this study were to evaluate the effects of 18-h fasting with low-carbohydrate diet (LCD) vs a minimum of 6-h fasting preparations on diffuse LV FDG uptake and free fatty acid (FFA) levels in patients with suspected CS. MethodsEighty-two patients with suspected CS were divided into 2 preparation protocols: one with a minimum 6-h fast without LCD preparation (group A, n = 58) and the other with a minimum 18-h fast with LCD preparation (group B, n = 24). All patients also received intravenous unfractionated heparin (UFH; 50 IU/kg) before the injection of FDG. ResultsGroup A showed a higher percentage of diffuse LV uptake than did group B (27.6 vs 0.0%, P = .0041). Group B showed higher FFA levels (1159.1 ± 393.0, 650.5 ± 310.9 μEq/L, P < .0001) than did group A. Patients with diffuse LV uptake (n = 16) showed lower FFA levels than did other patients (n = 66) (432.1 ± 296.1, 888.4 ± 381.4 μEq/L, P < .0001). UFH administration significantly increased FFAs in both groups, even in the patients with diffuse LV FDG uptake. ConclusionsThe 18-h fast with LCD preparation significantly reduced diffuse LV uptake and increased FFA levels. In particular, the FFA level was significantly lower in patients with LV diffuse uptake than in patients without LV diffuse uptake. Acutely increasing plasma FFA through the use of UFH may not have a significant role in reducing physiological LV FDG uptake.

Short communication: Lipolytic activity on milk fat by Staphylococcus aureus and Streptococcus agalactiae strains commonly isolated in Swedish dairy herds

The objective of this study was to determine the lipolytic activity on milk fat of 2 bovine mastitis pathogens, that is, Staphylococcus aureus and Streptococcus agalactiae. The lipolytic activity was determined by 2 different techniques, that is, thin-layer chromatography and an extraction-titration method, in an experimental model using the most commonly occurring field strains of the 2 mastitic bacteria isolated from Swedish dairy farms. The microorganisms were inoculated into bacteria-free control milk and incubated at 37°C to reflect physiological temperatures in the mammary gland. Levels of free fatty acids (FFA) were analyzed at time of inoculation (t=0) and after 2 and 6h of incubation, showing significant increase in FFA levels. After 2h the FFA content had increased by approximately 40% in milk samples inoculated with Staph. aureus and Strep. agalactiae, and at 6h the pathogens had increased FFA levels by 47% compared with the bacteria-free control milk. Changes in lipid composition compared with the bacteria-free control were investigated at 2 and 6h of incubation. Diacylglycerols, triacylglycerols, and phospholipids increased significantly after 6h incubation with the mastitis bacteria, whereas cholesterol and sterol esters decreased. Our results suggest that during mammary infections with Staph. aureus and Strep. agalactiae, the action of lipases originating from the mastitis pathogens will contribute significantly to milk fat lipolysis and thus to raw milk deterioration.

Adipose Triglyceride Lipase and G0/G1 Switch Gene 2: Approaching Proof of Concept

Fatty acids, stored as triglyceride, constitute the largest energy depot in the human body. It has been estimated that fat mass comprises around 20–30% of the entire body mass in Western populations (1). In terms of energy regulation, release of substrates from this huge energy reservoir may be viewed as one of the—if not the —principal metabolic process in the body. Clearly, mechanisms regulating mobilization of fatty acids—those regulating lipolysis—are of seminal interest. In line with this concept, free fatty acids (FFAs) in the circulation have decisive actions. Under conditions of stress, such as prolonged fasting, lipolysis is stimulated and FFAs are released into the blood. This response diverts the body from use of carbohydrate and protein fuels, and directs it to use fat, thereby preserving vital protein stores (2). Under postprandial conditions, which are habitual in modern societies, insulin secretion is stimulated and lipolysis is restricted. This leads to low levels of FFAs and increased utilization of carbohydrate and protein fuels. However, when insulin fails to reduce lipolysis adequately, increased FFA levels induce insulin resistance and lead to development of the metabolic syndrome and eventually type 2 diabetes (3–6). Mobilization of fat involves the sequential action of three lipases (7) (Fig. 1 A ). The rate-limiting step is cleavage of the first ester bond in triglycerides (TGs) by adipose triglyceride lipase (ATGL), producing diacylglycerol (DG) and releasing one FFA. Subsequently, hormone sensitive lipase (HSL) and monoglyceride lipase (MGL) hydrolyze DG to monoacylglycerol (MG) and MG to glycerol and FFA, respectively. Thus, for each TG molecule, one glycerol and three FFA molecules can be exported to the circulation and delivered to recipient tissues where they can serve as metabolic substrates. …

Visual findings of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with cardiac sarcoidosis.

The purpose of this study was to evaluate the cardiac sarcoidosis (CS) activity according to the classified visual uptake pattern using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and assess the uptake pattern based on the free fatty acid (FFA) levels. Nineteen CS subjects who underwent (18)F-FDG PET/CT examinations with heparin loading (HL) were recruited to evaluate their CS activity. The (18)F-FDG uptake in the heart was classified into five categories ("none," "diffuse" and "diffuse at base," regarded as stable CS, and "focal" and "focal on diffuse," regarded as de novo or worsening CS). The subject data were compared with the (18)F-FDG PET/CT findings in 13 healthy volunteers. The FFA serum levels were assessed in 10 patients with CS and all volunteers. The sensitivity and specificity of (18)F-FDG PET/CT with HL were 75% (6/8) and 73% (8/11), respectively. The major pattern of cardiac (18)F-FDG uptake was "diffuse at base." Ten of the 32 subjects, including the control group, exhibited this pattern. The FFA serum levels before heparin administration were statistically significantly different between the patients with the "none" pattern and those with the "diffuse" and "diffuse at base" patterns. There were no significant correlations between the FFA serum levels after heparin administration and the (18)F-FDG uptake patterns. "Diffuse at base" is the major (18)F-FDG uptake pattern associated with inadequate physiologic (18)F-FDG suppression. This pattern should be carefully interpreted when examining the (18)F-FDG PET/CT images of CS patients. Additionally, increased FFAs levels associated with HL may not completely suppress the physiologic myocardial FDG uptake.

Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial

Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was to compare the effects of endurance training with erythropoiesis-stimulating agent (ESA) treatment in healthy humans. Thirty-six healthy untrained men were randomized to 10 wk of either: 1) placebo (n = 9), 2) ESA (n = 9), 3) endurance training (n = 10), or 4) ESA and endurance training (n = 8). In a single-blinded design, ESA/placebo was injected one time weekly. Training consisted of biking for 1 h at 65% of wattmax three times per week. Measurements performed before and after the intervention were as follows: body composition, maximal oxygen uptake, insulin sensitivity, REE, and palmitate turnover. Uncoupling protein 2 (UCP2) mRNA levels were assessed in skeletal muscle. Fat mass decreased after training (P = 0.003), whereas ESA induced a small but significant increase in intrahepatic fat (P = 0.025). Serum free fatty acid (FFA) levels and palmitate turnover decreased significantly in response to training, whereas the opposite pattern was found after ESA. REE corrected for lean body mass increased in response to ESA and training, and muscle UCP2 mRNA levels increased after ESA (P = 0.035). Insulin sensitivity increased only after training (P = 0.011). 1) insulin sensitivity is not improved after ESA treatment despite improved exercise capacity, 2) the calorigenic effects of ESA may be related to increased UCP2 gene expression in skeletal muscle, and 3) training and ESA exert opposite effects on lipolysis under basal conditions, increased FFA levels and liver fat fraction was observed after ESA treatment.

Relationship between free fatty acids, insulin resistance markers, and oxidized lipoproteins in myocardial infarction and acute left ventricular failure

BackgroundThe most common cause of myocardial infarction (MI) is stenotic atherosclerotic lesions in subepicardial coronary arteries. Artery disease progression induces clinical signs and symptoms, among which MI is the leader in mortality and morbidity. Recent studies have been trying to find new biochemical markers that could predict the evolution of clinical complications; among those markers, free fatty acids (FFA) and oxidative modification of low-density lipoproteins (oxidized LDL) have a special place.Materials and methodsSeventy-nine ST-elevation MI patients were enrolled. The first group included MI patients without the signs of acute heart failure (Killip class I) while MI patients with Killip classes II–IV made up the second group. Thirty-three individuals with no cardiovascular disease were the controls. The lipid profile, serum oxidized LDL, and their antibodies, C-peptide and insulin were measured at days 1 and 12. The level of insulin resistance was assessed with the quantitative insulin sensitivity check index (QUICKI).ResultsMI patients had atherogenic dyslipidemia; however, the Killip II–IV group had the most pronounced and prolonged increase in FFA, oxidized LDL, and their antibodies. Additionally, positive correlations between FFA levels and creatine kinase activity (12 days, R = 0.301; P = 0.001) and negative correlations between the QUICKI index and FFA levels (R = −0.46; P = 0.0013 and R = −0.5; P = 0.01) were observed in the both groups.ConclusionThe development of MI complications is accompanied by a significant increase in FFA levels, which not only demonstrate myocardial injury, but also take part in development of insulin resistance. Measuring FFA levels can have a great prognostic potential for risk stratification of both acute and recurrent coronary events and choice of treatment strategy.

Time-course effects of physiological free fatty acid surges on insulin sensitivity in humans

Physiological elevations of free fatty acids (FFAs) occur in bell-shaped surges lasting some hours, observed nocturnally, during exercise and inflammation. The time-course effects of such FFA surges on insulin sensitivity are unknown. We therefore aimed to define the effects of a graded 4-h FFA elevation intended to mimick physiological excursions. Eight lean, healthy men were studied on two occasions: (1) control (saline) and (2) 4 h graded infusion of intralipid (20%)/heparin. Insulin sensitivity was continuously assessed by isotope dilution (3H-glucose) during an 8 h hyperinsulinemic-euglycaemic clamp (0.5 mU kg(-1) min(-1) ). Phosphorylation of Akt and ERK1/2 was measured in muscle biopsies taken at 0 and 120 min. Inflammatory cytokines were assessed with a Luminex Suspension Array System. Infusion of intralipid caused a bell-shaped increase in FFA levels reaching peak levels ~1.9 mmol L(-1) and markedly impairing insulin sensitivity. Impairment of insulin sensitivity was apparent (P>0.05) 120 min after initiation of FFA infusion, significant after 270 min (P < 0.001) and peaked after 360 min. FFA induced insulin resistance prevailed 210 min after cessation of FFA infusion. No effect was observed on Akt and ERK1/2 phosphorylation. (1) Physiological FFA elevations require at least 120 min to induce insulin resistance, (2) that insulin resistance peaks 360 min after initiation of FFA exposure and (3) ceases 210 min after termination of the FFA infusion. These observations add to our understanding of FFA induced insulin resistance in relation to circadian variations, exercise, generalized inflammation and exposure to stress hormones such as growth hormone.