High Levels Of Free Fatty Acids Research Articles

Free fatty acid levels in fluid of dominant follicles at the preferred insemination time in dairy cows are not affected by early postpartum fatty acid stress

The fertility of high-yielding dairy cows has declined during the last 3 decades, in association with a more profound negative energy balance (NEB) during the early weeks postpartum. One feature of this NEB is a marked elevation in circulating free fatty acid (FFA) concentrations. During the early postpartum period (≤d 42), circulatory FFA levels were measured weekly, and progesterone concentrations and the diameter of the dominant follicles were determined thrice weekly. Retrospectively, cows that ovulated within 35 d postpartum were grouped as “normal ovulating” cows (n=5), and the others were grouped as “delayed ovulating” cows (n=5). In both groups, high total FFA levels (>500 µM) were evident immediately postpartum. Interestingly, cows with delayed ovulation had higher plasma FFA concentrations in the first weeks postpartum compared with normal ovulating cows. In both cow groups, FFA decreased to control levels of non-NEB cows within 3 wk postpartum. The FFA compositions and concentrations in fluids from the dominant follicles of postpartum cows were not different between the normal and delayed ovulating cows when measured at potential insemination points: d 55, 80, and 105 postpartum. Interestingly, the concentration of monounsaturated oleic acid was higher and that of saturated stearic acid lower in follicular fluids of both groups compared with that in blood. The level of FFA in follicular fluid was correlated with the ratio of 17β-estradiol (E2) to progesterone (P4) in follicular fluid, with a relatively high level of unsaturated FFA in follicles with a low E2:P4 ratio. Taken together, these results indicate that a more severe NEB early postpartum is related to a delay in the first postpartum ovulation and does not affect FFA composition in follicular fluid at the preferred insemination time. The high FFA level in dominant follicles with a low E2:P4 ratio may be due to a different FFA metabolism in these follicles. The diagnostic value of this observation for selective screening of dominant follicles needs further investigation.

Induction of Haemeoxygenase-1 Improves FFA-Induced Endothelial Dysfunction in Rat Aorta

Background: The induction of haemeoxygenase-1 (HO-1) exerts beneficial effects in the setting of endothelial dysfunction in obesity. High free fatty acid (FFA) levels are a common feature of obesity and are the primary cause of endothelial dysfunction. The objective of our study was to explore the effects of HO-1 induction on FFA-induced endothelial dysfunction in rats. Methods: Rats received FFA treatment with either cobalt protoporphyrin (CoPP) to induce HO-1 or stannous protoporphyrin (SnPP) to inhibit HO-1. Endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) production, superoxide production and nuclear factor <smlcap>(NF)-</smlcap>κ<smlcap>B </smlcap>expression in the aorta were each determined. The levels of adenosine monophosphate (AMP)-activated kinase (AMPK) and endothelial nitric oxide synthase (eNOS) expression in endothelial cells were determined via Western blotting. Results: Induction of HO-1 by CoPP decreased circulating FFA, high-sensitivity C-reactive protein and malondialdehyde levels and increased serum adiponectin and glutathione levels compared with the FFA group (P<0.05). High FFA levels resulted in EDV impairment, which was improved by HO-1 induction (P<0.05). Induction of HO-1 increased NO levels and reduced aortic superoxide production and <smlcap>NF-</smlcap>κ<smlcap>B </smlcap>expression compared with the FFA group. The FFA group exhibited decreased AMPK expression and eNOS phosphorylation, both of which were enhanced via HO-1 induction (P<0.05). The beneficial effects of CoPP on EDV were partially attenuated in vitro in the presence of inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K), and eNOS. Conclusions: HO-1 induction with CoPP improves FFA-induced endothelial dysfunction in the rat aorta. The protective mechanism appears to be related to the activation of the AMPK-PI3K-eNOS pathway as a result of increased adiponectin levels as well as decreased inflammation and oxidative stress.

Free Fatty Acids Impair FGF21 Action in HepG2 Cells

Background/Aims: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). Methods: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. Results: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. Conclusion: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

Plasma free fatty acid levels influence Zn2+‐dependent histidine‐rich glycoprotein–heparin interactions via an allosteric switch on serum albumin

BackgroundHistidine-rich glycoprotein (HRG) regulates coagulation through its ability to bind and neutralize heparins. HRG associates with Zn2+ to stimulate HRG–heparin complex formation. Under normal conditions, the majority of plasma Zn2+ associates with human serum albumin (HSA). However, free fatty acids (FFAs) allosterically disrupt Zn2+ binding to HSA. Thus, high levels of circulating FFAs, as are associated with diabetes, obesity, and cancer, may increase the proportion of plasma Zn2+ associated with HRG, contributing to an increased risk of thrombotic disease.ObjectivesTo characterize Zn2+ binding by HRG, examine the influence that FFAs have on Zn2+ binding by HSA, and establish whether FFA-mediated displacement of Zn2+ from HSA may influence HRG–heparin complex formation.MethodsZn2+ binding to HRG and to HSA in the presence of different FFA (myristate) concentrations were examined by isothermal titration calorimetry (ITC) and the formation of HRG–heparin complexes in the presence of different Zn2+ concentrations by both ITC and ELISA.Results and conclusionsWe found that HRG possesses 10 Zn2+ sites (K′ = 1.63 × 105) and that cumulative binding of FFA to HSA perturbed its ability to bind Zn2+. Also Zn2+ binding was shown to increase the affinity with which HRG interacts with unfractionated heparins, but had no effect on its interaction with low molecular weight heparin (˜ 6850 Da). [Correction added on 1 December 2014, after first online publication: In the preceding sentence, “6850 kDa” was corrected to “6850 Da”.] Speciation modeling of plasma Zn2+ based on the data obtained suggests that FFA-mediated displacement of Zn2+ from serum albumin would be likely to contribute to the development of thrombotic complications in individuals with high plasma FFA levels.

Fatty acid oxidation changes and the correlation with oxidative stress in different preeclampsia-like mouse models.

BackgroundLong-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression is decreased in placenta of some cases of preeclampsia (PE) which may result in free fatty acid (FFA) increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway.MethodsPE-like groups were ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of Nw-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS) and the antiphospholipid syndrome (APS) mouse model with β2GPI injection (ApoC3+NS, ApoC3+L-NA, L-NA, LPS and β2GPI groups). The control group was wild-type mice with normal saline injection. Except for β2GPI mice, the other mice were subdivided into pre-implantation (Pre) and mid-pregnancy (Mid) subgroups by injection time.ResultsAll PE-like groups showed hypertension and proteinuria except ApoC3+NS mice only showed hypertension. Serum FFA levels increased significantly except in LPS group compared to controls (P<0.05). LCHAD mRNA and protein expression in the liver and placenta was significantly higher for ApoC3+NS, ApoC3+L-NA and β2GPI mice and lower for L-NA mice than controls (P<0.05) but did not differ between LPS mice and controls. P47phox mRNA and protein expression in the liver significantly increased in all PE-like groups except LPS group, while P47phox expression in the placenta only significantly increased in L-NA and β2GPI groups.ConclusionsAbnormal long-chain fatty acid-oxidation may play a different role in different PE-like models and in some cases participate in the pathogenesis of PE through oxidative stress pathway.

Intensification of waste cooking oil transformation by transesterification and esterification reactions in oscillatory baffled and microstructured reactors for biodiesel production

Abstract The transformation of waste cooking oils for fatty acid methyl ester production is investigated in two intensified technologies: microstructured Corning® and oscillatory baffled NiTech® reactors, compared to a reference batch reactor to quantify the process intensification provided by each technology. Both reactors achieve high conversions in shorter times. For transesterification, 96 wt.% of esters are obtained in 1.4 min at 97°C in the Corning® reactor and 92.1 wt.% of esters in 6 min at 44°C in the NiTech® reactor, compared with 94.8 wt.% of esters in 10 min at 60°C in the batch reactor. For esterification, 92% conversion is obtained in 2.5 min in the Corning® reactor at 75°C compared with 20–30 min in the batch reactor at 60°C, and at 40°C, 96.8% conversion is achieved in 13.3 min in the NiTech® reactor, compared with 30 min in the batch reactor. The advantage of the Corning® reactor is that it can operate at higher pressures (1–20 bar) and temperatures (100°C), thereby providing faster kinetics than the NiTech® reactor. However, oils with a high free fatty acid level (73%) cause the Corning® reactor channels to be blocked. A wider range of operating conditions could be obtained in NiTech® with a pressure-resistant material.

Epidermal fatty acid-binding protein protects nerve growth factor-differentiated PC12 cells from lipotoxic injury.

Epidermal fatty acid-binding protein (E-FABP/FABP5/DA11) binds and transport long-chain fatty acids in the cytoplasm and may play a protecting role during neuronal injury. We examined whether E-FABP protects nerve growth factor-differentiated PC12 cells (NGFDPC12 cells) from lipotoxic injury observed after palmitic acid (C16:0; PAM) overload. NGFDPC12 cells cultures treated with PAM/bovine serum albumin at 0.3 mM/0.15 mM show PAM-induced lipotoxicity (PAM-LTx) and apoptosis. The apoptosis was preceded by a cellular accumulation of reactive oxygen species (ROS) and higher levels of E-FABP. Antioxidants MCI-186 and N-acetyl cysteine prevented E-FABP's induction in expression by PAM-LTx, while tert-butyl hydroperoxide increased ROS and E-FABP expression. Non-metabolized methyl ester of PAM, methyl palmitic acid (mPAM), failed to increase cellular ROS, E-FABP gene expression, or trigger apoptosis. Treatment of NGFDPC12 cultures with siE-FABP showed reduced E-FABP levels correlating with higher accumulation of ROS and cell death after exposure to PAM. In contrast, increasing E-FABP cellular levels by pre-loading the cells with recombinant E-FABP diminished the PAM-induced ROS and cell death. Finally, agonists for PPARβ (GW0742) or PPARγ (GW1929) increased E-FABP expression and enhanced the resistance of NGFDPC12 cells to PAM-LTx. We conclude that E-FABP protects NGFDPC12 cells from lipotoxic injury through mechanisms that involve reduction of ROS.Epidermal fatty acid-binding protein (E-FABP) may protect nerve cells from the damaging exposure to high levels of free fatty acids (FA). We show that E-FABP can neutralize the effects of reactive oxygen species (ROS) generated by the high levels of FA in the cell and protect PC12 cells from lipotoxic injuries common in Type 2 diabetes neuropathy. Potentially, E-FABP gene up-regulation may be mediated through the NFkB pathway and future studies are needed to further evaluate this proposition.

4‐Phenylbutyrate protects renal proximal tubular cells from palmitic acid‐induced endoplasmic reticulum stress and cell death (1063.2)

Obesity is implicated as a significant risk factor for chronic kidney disease (CKD). High plasma free fatty acid levels observed with obesity impairs the endoplasmic reticulum (ER) and cause ER stress. Chemical chaperones, which relieve ER stress, such as 4‐phenylbutyrate (4‐PBA) have been shown to protect the liver and pancreas against obesity‐induced organ damage; however, their protective role in obesity‐induced renal damage is unknown. Thus, we investigated the nephroprotective role of 4‐PBA in an in vitro model of palmitic acid (PA)‐induced ER stress and renal injury using normal rat kidney cells (NRK‐52E). Cells were divided into four groups: Control, 250 μM PA‐treated, 5 mM 4‐PBA‐treated, and 4‐PBA+PA co‐treated. After 24 h of PA and/or 4‐PBA treatments, cell viability and caspase‐3/7 activity (a marker of apoptosis) were determined. Immunoblot analyses were performed to quantitate the levels of ER stress markers ‐ glucose‐regulated protein (GRP78) and C/EBP homologous protein (CHOP) ‐ in renal cells. Exposure to PA significantly reduced the viability (81.3% to that of control) in NRK‐52E cells, and markedly increased the activity of caspase‐3/7 activity (2‐fold increase over control) and the expression of ER stress markers GRP78 and CHOP (1.6 and 2 folds over control respectively) at P‐value &lt; 0.05. Intriguingly, cells treated with 4‐PBA were protected from PA‐induced ER stress and apoptotic cell death. Our studies demonstrate that 4‐PBA acts as nephroprotectant and prevents fatty acid‐induced ER stress and apoptosis in renal cells. Further investigations in vivo are required to validate the therapeutic potential of 4‐PBA to protect the kidney and prevent the development of CKD during obesity.Grant Funding Source: Supported by Qatar Univ. Student Research Grants # QUST‐CPH‐FALL‐12/13‐6 and QUST‐CPH‐SPR‐12/13‐3.

Association of adiponectin, free fatty acids, and insulin resistance with metabolic syndrome and its components in Uygur Xinjiang province

Objective To investigate the association of adiponectin (APN),free fatty acids (FFA),and insulin resistance(IR) with metabolic syndrome (MS) and its components.Methods In the baseline survey,the subjects were divided into MS group and the control group based on the criteria of 2005 International Diabetes Federation,and randomly selected 218 and 201 cases for the study.APN was measured by ELISA,FFA by colorimetry,fasting insulin by radioimmunoassay.Results FFA and IR were significantly higher in subjects with MS than that without MS,while APN was lower(P＜0.01).FFA and IR rose gradually along with the increased number of MS components(P＜0.01),while APN descended.The incidence and risk of MS and its abnormal components were significantly higher in the Q4 group with higher level of FFA and raised IR when compared to the Q1 group with lower level(P＜0.01),but the APN finding was the opposite(P＜0.01).After adjusting for other factors,APN,FFA,and IR were still associated with MS by using logistic regression analysis.Conclusions The level of FFA and state of IR was raised in subjects with MS,as well as with the increase in number of MS components,but the finding was the opposite as regard to APN.Serum APN,FFA,and IR may each play important roles in development of MS. Key words: Uygur ; Metabolic syndrome ; Adiponectin ; Free fatty acids ; Insulin resistance

Polyphenol-rich fruits attenuate impaired endothelial function induced by glucose and free fatty acids in vitro in human endothelial cells

Elevated concentrations of plasma glucose and free fatty acids (FFA) are associated with impaired endothelial function increasing risk of cardiovascular diseases. Previous studies suggested that fruits rich in polyphenolic compounds modulate endothelial cell migration and capillary-like tube formation via a redox-sensitive mechanism. We hypothesized that polyphenol-rich extracts of strawberry (SB) and wild blueberry (WB) would attenuate relatively high concentrations of glucose and/or FFA-mediated impaired cell migration and capillary-like tube formation in vitro in human umbilical vein endothelial cells (HUVECs). HUVECs treated with high FFA and combina- tions of glucose and FFA showed significantly reduced cell migration and capillary-like tube formation compared to the PBS control (p<0.05). However, HUVEC pre-treated with SB or WB extracts significantly increased cell migration and capillary-like tube formation in cells treated with FFA or a combination of FFA and glucose compared to cells exposed to the same nutrients/combinations alone. The results from this study suggest that berry fruits may play a role in promoting cardiovascular health especially in individuals with high blood glucose and/or FFA levels.

Current status of lower-extremity revascularization

This study aimed to investigate the relationship between pre-procedure high-sensitivity C-reactive protein (hsCRP), free fatty acid (FFA), and uric acid (UA) levels and post-procedure mortality and morbidity of endovascular revascularization of arterial femoropopliteal occlusion lesions.This was a retrospective review of clinical data retrieved from a prospectively held database in Peking Union Medical College Hospital. A total of 71 Patients who underwent endovascular treatment (EVT) for femoropopliteal occlusive disease between January 1, 2014 and November 1, 2017, were included in this study. Endpoints were defined as major adverse limb events (MALE; target vessel revascularization, amputation, or disease progression) and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or all-cause death) during the entire follow-up period. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the relationship of elevated biomarker levels (hsCRP, FFA and UA, measured by immunoturbidimetry assay, enzymatic assay and enzymatic assay, respectively) to MALE and MACE outcomes.Seventy-one patients (72 limbs) with sufficient follow-up information were included in the analysis. The mean age was 69.7 ± 8.6 years; 21.1% were female. The Rutherford class of target limbs were ≥ 3. The median follow-up was 36 (range 18-59 months). Univariate analyses revealed that patients with elevated hsCRP levels had an increased risk of MALE (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.281-5.617, P = 0.009). High FFA levels were associated with an increased risk of MALE (HR, 2.658; 95% CI, 1.075-6.573; P = 0.034). Multivariate analyses demonstrated that elevated hsCRP values (HR, 4.015; 95% CI, 1.628-10.551; P = 0.003) and FFA value (HR, 3.034; 95% CI, 1.102-8.354; P = 0.032) were both significantly associated with increased MALE. Elevated UA levels predicted MACE in the presence of confounders (HR, 11.446; 95% CI, 1.367-95.801 P = 0.023).Pre-procedure hsCRP and FFA levels could serve as predictors of adverse events after EVT in patients with arterial femoropopliteal occlusive disease. The role of UA in MACE may warrant further investigation, because the correlation is not as powerful as the other two in the study.

High free fatty acid level is associated with recurrent stroke in cardioembolic stroke patients

To determine whether the plasma level of free fatty acid (FFA) could be associated with recurrent stroke in cardioembolic (CE) stroke patients. We analyzed data from 669 acute ischemic stroke patients and examined the association between FFA concentration and recurrent stroke in CE stroke patients compared with non-CE stroke patients. The baseline plasma FFA concentration (mEq/L) was approximately 1.5-fold higher in CE stroke patients (1.01 ± 0.63) than in non-CE stroke patients (0.72 ± 0.51). Multivariate logistic analysis showed that an increased level of FFA was significantly associated with CE stroke (hazard ratio [HR] 2.124, confidence interval [CI] 1.492-3.024). During the mean follow-up period of 25.4 months, a total of 56 (8.4%) patients experienced a stroke recurrence. The recurrence rate did not differ between patients with CE (10.5%) and non-CE (8.0%) stroke (p = 0.396). In CE stroke patients, an elevated baseline FFA concentration was independently associated with stroke recurrence (HR 2.711, CI 1.056-6.959). However, there was no association between FFA and stroke recurrence in non-CE stroke patients. In this retrospective registry-based observational study, CE stroke seemed to be associated with elevated plasma level of FFA. In addition, the present study suggested that an elevated FFA concentration could be a useful indicator for predicting recurrent stroke in CE stroke patients.

α/β-hydrolase domain containing protein 15 (ABHD15)--an adipogenic protein protecting from apoptosis.

Our knowledge about adipocyte metabolism and development is steadily growing, yet many players are still undefined. Here, we show that α/β-hydrolase domain containing protein 15 (Abhd15) is a direct and functional target gene of peroxisome proliferator-activated receptor gamma (PPARγ), the master regulator of adipogenesis. In line, Abhd15 is mainly expressed in brown and white adipose tissue and strongly upregulated during adipogenesis in various murine and human cell lines. Stable knockdown of Abhd15 in 3T3-L1 cells evokes a striking differentiation defect, as evidenced by low lipid accumulation and decreased expression of adipocyte marker genes. In preconfluent cells, knockdown of Abhd15 leads to impaired proliferation, which is caused by apoptosis, as we see an increased SubG1 peak, caspase 3/7 activity, and BAX protein expression as well as a reduction in anti-apoptotic BCL-2 protein. Furthermore, apoptosis-inducing amounts of palmitic acid evoke a massive increase of Abhd15 expression, proposing an apoptosis-protecting role for ABHD15. On the other hand, in mature adipocytes physiological (i.e. non-apoptotic) concentrations of palmitic acid down-regulate Abhd15 expression. Accordingly, we found that the expression of Abhd15 in adipose tissue is reduced in physiological situations with high free fatty acid levels, like high-fat diet, fasting, and aging as well as in genetically obese mice. Collectively, our results position ABHD15 as an essential component in the development of adipocytes as well as in apoptosis, thereby connecting two substantial factors in the regulation of adipocyte number and size. Together with its intricate regulation by free fatty acids, ABHD15 might be an intriguing new target in obesity and diabetes research.

The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial (18)F-FDG Uptake in Normal Humans.

In a whole-body (18)F-FDG PET/CT, non-specific (18)F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial (18)F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before (18)F-FDG injection from all subjects. Myocardial (18)F-FDG uptake was measured as the mean (SUVmean) and maximal (SUVmax) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI). We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28 ± 8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUVmax was 4.57, respectively and there was a strong linear correlation between SUVmean and SUVmax (r = 0.98). FFA and fasting duration showed significant negative correlation with myocardial (18)F-FDG uptake, respectively (r = -0.40 in FFA; r = -0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial (18)F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve (18)F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

Effect of high free fatty acids on the anti-contractile response of perivascular adipose tissue in rat aorta

To determine whether high free fatty acids (FFA) could affect the anti-contractile properties of perivascular adipose tissue (PVAT) in rat aortas. Wistar rats were divided into normal, obesity and fenofibrate groups and fed a normal, high-fat, and high-fat plus fenofibrate diet, respectively. Thoracic aortas with or without PVAT (PVAT+ and PVAT−) were prepared with either intact endothelium (E+) or with endothelium removed (E−). Aortas pre-treated with either 500μmol/L of palmitic acid (PA) or physiological salt solution (PSS), as a control, were used for in vitro study. Concentration-dependent responses of aortas to norepinephrine were measured. The anti-contractile effects of PVAT were attenuated in both obese rats with high FFA levels and in the PA group in the presence of endothelium, but not in the absence of endothelium. The attenuation of the anti-contractile effect was restored by reducing FFA levels in the fenofibrate group (P<0.05). Incubation of aortas (PVAT+ E+) with nitric oxide (NO) synthase inhibitor and tumor necrosis factor-alpha (TNF-α) in the normal group caused attenuation of the anti-contractile effect of PVAT (P<0.05). Incubation of aortas (PVAT+ E+) in the obese and PA groups with a NO donor, anti-TNF-α antibodies or free radical scavengers partially restored the anti-contractile effect of PVAT (P<0.05). Under both acute and chronic conditions, high FFA levels could attenuate the anti-contractile properties of PVAT by an endothelium-dependent rather than an endothelium-independent mechanism, in which inflammation and oxidative stress may play important roles.

Blocking the Entrance to Open the Gate

Almost 80% of postprandial glucose uptake resides in skeletal muscle (1). Hence, development of skeletal muscle insulin resistance is a hallmark of type 2 diabetes. Muscle is an ambiguous organ with respect to substrate selection. To fuel muscle contraction, both glucose and fatty acids can be oxidized. Glucose first needs to enter the muscle cells via insulin-mediated GLUT4-dependent transmembrane transport and then be converted to acetyl-CoA via the pyruvate dehydrogenase (PDH) complex. Oxidation of fatty acids, especially long-chain fatty acids, requires mitochondrial entrance via carnitine palmitoyltransferase-1 (CPT-1) prior to subsequent β-oxidation. To explain the well-known relationship between obesity and type 2 diabetes, Sir Philip Randle (2) proposed in 1963 that high uptake of fatty acids in skeletal muscle resulting from high free fatty acid levels observed in obesity would result in high fatty acid oxidation rates (Fig. 1). In turn, this would reduce glucose oxidation, thereby rendering the muscle insulin resistant. At the cellular level, high rates of fatty acid oxidation would result in accumulation of acetyl-CoA and citrate, thereby inhibiting PDH and glycolysis, ultimately resulting in reduced glucose oxidation. However, in the previous 2 decades, the concept of the Randle cycle in skeletal muscle has been challenged. Elegant studies by Shulman and colleagues (3–5) showed that in type 2 diabetes, reduced uptake of glucose due to compromised GLUT4 translocation, not a reduced glycolytic flux, is the main culprit in development of skeletal muscle insulin resistance. Moreover, fat accumulation in muscle, and particularly accumulation of muscle diacylglycerol (DAG), was suggested to impair …

Systemic β-Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans

Brown adipose tissue (BAT) is currently considered as a target to combat obesity and diabetes in humans. BAT is densely innervated by the sympathetic nervous system (SNS) and can be stimulated by β-adrenergic agonists, at least in animals. However, the exact role of the β-adrenergic part of the SNS in BAT activation in humans is not known yet. In this study, we measured BAT activity by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography/computed tomography imaging in 10 lean men during systemic infusion of the nonselective β-agonist isoprenaline (ISO) and compared this with cold-activated BAT activity. ISO successfully mimicked sympathetic stimulation as shown by increased cardiovascular and metabolic activity. Energy expenditure increased to similar levels as during cold exposure. Surprisingly, BAT was not activated during β-adrenergic stimulation. We next examined whether the high plasma free fatty acid (FFA) levels induced by ISO competed with glucose ([18F]FDG) uptake in BAT locations by blocking lipolysis with acipimox (ACI). ACI successfully lowered plasma FFA, but did not increase [18F]FDG-uptake in BAT. We therefore conclude that systemic nonselective β-adrenergic stimulation by ISO at concentrations that increase energy expenditure to the same extent as cold exposure does not activate BAT in humans, indicating that other tissues are responsible for the increased β-adrenergic thermogenesis.

Adipose Tissue TCF7L2 Splicing Is Regulated by Weight Loss and Associates With Glucose and Fatty Acid Metabolism

We investigated the effects of obesity surgery-induced weight loss on transcription factor 7-like 2 gene (TCF7L2) alternative splicing in adipose tissue and liver. Furthermore, we determined the association of TCF7L2 splicing with the levels of plasma glucose and serum free fatty acids (FFAs) in three independent studies (n = 216). Expression of the short mRNA variant, lacking exons 12, 13, and 13a, decreased after weight loss in subcutaneous fat (n = 46) and liver (n = 11) and was more common in subcutaneous fat of subjects with type 2 diabetes than in subjects with normal glucose tolerance in obese individuals (n = 54) and a population-based sample (n = 49). Additionally, there was a positive correlation between this variant and the level of fasting glucose in nondiabetic individuals (n = 113). This association between TCF7L2 splicing and plasma glucose was independent of the TCF7L2 genotype. Finally, this variant was associated with high levels of serum FFAs during hyperinsulinemia, suggesting impaired insulin action in adipose tissue, whereas no association with insulin secretion or insulin-stimulated whole-body glucose uptake was observed. Our study shows that the short TCF7L2 mRNA variant in subcutaneous fat is regulated by weight loss and is associated with hyperglycemia and impaired insulin action in adipose tissue.

An investigation of restaurant waste oil characteristics for biodiesel production in Trinidad and Tobago

In this study, the effect of cooking conditions on waste oil characteristics and yield of methyl esters was investigated for biodiesel production in Trinidad and Tobago. Used cooking oil was collected from eleven restaurants that were subdivided into four categories according to the type of meals served: four Chinese restaurants, four Indian restaurants, two Fried-Chicken restaurants and one Pizzeria. The waste oils were characterised as to their acid value, free fatty acid levels, saponification, peroxide value, water concentrations and fatty acid composition. Waste oil from one restaurant from each category was then selected to undergo base catalysed transesterification. The waste oils collected from the Indian restaurants were used less intensely and had the most desirable properties with the lowest free fatty acid content while those of the Chinese restaurants produced the highest yields of methyl esters. Biodiesel produced from the waste oil of these two restaurants also met the ASTM standard for the properties tested. Waste oils from the Fried-Chicken restaurants and the Pizzeria demonstrated high degradation that was reflected in their high acid values and free fatty acid levels and correspondingly poor yields of methyl esters. Given the high proportion of these less suitable waste oil feedstocks in the local market, biodiesel production via base catalysed transesterification may not be suitable in the Trinidad and Tobago context.

California Almond Shelf Life: Lipid Deterioration During Storage

The effects of storage conditions on the lipid deterioration in California almond nuts and sliced were studied. Natural whole almonds with or without polyethylene (PE) packaging and blanched whole almonds and sliced with PE packaging were stored in 10 different storage conditions which were combinations of different temperatures and relative humidity levels. The peroxide values (PVs), iodine values (IVs), and free fatty acids (FFAs) were monitored during the storage. The PVs in the natural samples did not change noticeably whereas the blanched samples changed greatly, indicating that skins may have played a significant role. The IVs decreased slightly in the 1st 150 d of storage and then leveled off. The slightly faster changes in IVs in the blanched samples coincided with the greater changes in PVs in the blanched samples. The natural samples exhibited much higher FFA levels than the blanched samples after storage. In general, FFA increased with increasing storage time, temperature, and humidity. Highest levels of FFA were observed in the samples stored at high temperature and high humidity. The results reported in this article provide useful information that almond producers and processors could use to develop their storage and transport processes.