Lower Free Fatty Acid Levels Research Articles

Ecological adaptations of amphibians to environmental changes along an altitudinal gradient (Case Study: Bufo gargarizans) from phenotypic and genetic perspectives

BackgroundOrganisms have evolved a range of phenotypic and genetic adaptations to live in different environments along an altitudinal gradient. Herein, we studied the widely distributed Chinese toad, Bufo gargarizans, as a model and used an integrated phenotype-genotype approach to assess adaptations to different altitudinal environments.ResultsComparison of populations from four altitudes (50 m, 1200 m, 2300 m, and 3400 m) showed more effective defenses among high-altitude toads. These included thickened epidermis, more epidermal capillaries and granular glands, greater gland size in skin, and higher antioxidant enzyme activities in plasma. High-altitude toads also showed increased erythrocytes and hematocrit and elevated hemoglobin concentration, potentially improving oxygen delivery. Elevated altitude led to a metabolic shift from aerobic to anaerobic metabolism, and high-altitude populations favored carbohydrates over fatty acids to fuel for energy metabolism. Differentially expressed genes were associated with adaptive phenotypic changes. For instance, expression of genes associated with fatty acid metabolism showed greater suppression at high altitude (3400 m), consistent with decreased flux of β-hydroxybutyric acid and lower free fatty acids levels. Moreover, down-regulation of genes involved in carbon metabolism processes at high altitude (3400 m) were coincident with reduced TCA cycle flux. These results suggest that high-altitude toads adopt a metabolic suppression strategy for survival under harsh environmental conditions. Moreover, the hypoxia-inducible factor signaling cascade was activated at high altitude.ConclusionsCollectively, these results advance our comprehension of adaptation to high-altitude environments by revealing physiological and genetic mechanisms at work in Chinese toads living along altitudinal gradients.

The U -shape relationship between free fatty acid level and adverse outcomes in coronary artery disease patients with hypertension: evidence from a large prospective cohort study

BackgroundEvidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study.MethodsA large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups.ResultsA total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a “U -shape” relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240–3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495–4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077–1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013–1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187–2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070–1.798), P = 0.013).ConclusionsBaseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension.Trial registrationThe details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143).

The association between serum free fatty acid levels and neurological outcomes in out-of-hospital cardiac arrest patients: A prospective observational study.

Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. This prospective observational study included adult (≥18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 hour after ROSC and at 6, 12, 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 hour after ROSC (0.72 vs 1.01 mol/L), at 6 hours (1.19 vs 1.90 mol/L), 12 hours (1.20 vs 1.66 mol/L), and 24 hours (1.20 vs 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 hours (odds ratio, 0.583; 95% confidence interval, 0.370-0.919; P = .020), and 12 hours (odds ratio, 0.509; 95% confidence interval, 0.303-0.854; P = .011) after ROSC were independently associated with poor neurological outcomes. The lower FFA levels at 6 hours and 12 hours after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

Abstract 210: The Relationship Between Serum Free Fatty Acid Levels After the Return of Spontaneous Circulation and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients

Background: Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. Methods: This prospective observational study included adult (≥ 18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 h after ROSC and at 6 h, 12 h, 24 h, 48 h, and 72 h after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. Results: A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 h after ROSC (0.72 vs. 1.01 mol/L), at 6 h (1.19 vs. 1.90 mol/L), 12 h (1.20 vs. 1.66 mol/L), and 24 h (1.20 vs. 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 h (odds ratio [OR], 0.583; 95% confidence interval [CI], 0.370-0.919; P = 0.020), and 12 h (OR, 0.509; 95% CI, 0.303-0.854; P = 0.011) after ROSC were independently associated with poor neurological outcomes. Conclusions: The lower FFA levels at 6 h and 12 h after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

Preoperative Oral Carbohydrate Levels in Patients with Type 2 Diabetes Mellitus: The Clinical Guiding Significance of Free Fatty Acids.

BackgroundIt is still controversial whether preoperative oral carbohydrate (POC) should be applied to patients with type 2 diabetes mellitus (T2DM) in the enhanced recovery after surgery (ERAS) protocol. There is no relevant consensus or indicators to provide guidance as to whether T2DM patients should take POC.MethodsIn total, 164 T2DM patients who underwent laparoscopic hepatectomy were analyzed. According to the level of blood free fatty acids (FFAs) and whether the patients received POC, the patients were divided into 6 groups: the low FFA carbohydrate group (LFFAC group), low FFA fasting water group (LFFAF group), medium FFA carbohydrate group (MFFAC group), medium FFA fasting water group (MFFAF group), high FFA carbohydrate group (HFFAC group) and high FFA fasting water group (HFFAF group).ResultsPatients with low FFA levels showed better perioperative blood glucose control and a lower incidence of postoperative complications than those in the medium and high FFA groups, especially when patients received POC. Further analyses revealed that the postoperative plasma concentrations of IL-6 and TNF-α were significantly decreased in the POC group compared with the fasting water group, except for patients with high FFA levels. Receiver operating characteristic (ROC) curve analysis revealed that when the FFA concentration was higher than 0.745 mmol/L, the risk of poor blood glucose control during the perioperative period was increased.ConclusionsFFAs have clinical guiding significance for the application of POC in patients with T2DM under ERAS administration. T2DM patients with low FFAs are more suitable for receiving POC.

Techno-economics of coconut coir bioadsorbent utilization on free fatty acid level reduction in crude palm oil

The quality of crude palm oil (CPO) is generally determined by the levels of free fatty acids (FFA). This helps in balancing the level of acidity during transportation and storage processes. However, high FFA in CPO is not good for consumer health. One of the methods for adsorbing FFA is adsorption, which is the adhesion of atoms, ions, or molecules from a gas, liquid, or dissolved solid to a surface. Therefore, this study aims to analyze the effect of contact time (40, 80 and 120 min) and Coconut Coir (CC) bioadsorbent concentrations of 1, 2 and 3 (%, w/v) on the reduction of CPO FFA levels. This began with the activation of CC biochar synthesis by using NaOH and HCl, which produced CC-NaOH and CC-HCl bioadsorbents based on the product of NaOH. Furthermore, the adsorption process was carried out by mixing CPO with CC-NaOH and CC-HCl bioadsorbents in a three-necked flask. After this, the filtrate product was obtained and analyzed for its FFA levels. The results showed that the largest percentage reduction for the effect of bioadsorbent concentration was 3% (w/v) at a contact time of 120 min. It also indicated that this study enabled lower levels of FFA in CPO. Based on the detailed cost estimate, the production cost of the CC-NaOH bioadsorbent was USD 481,874, sold at USD 95/ton with annual sales and net profit (after tax) at USD 684,000 and USD 141,188, respectively. This profit after tax and rate of return on investment was found to be 20.68 and 39.49% of the entire estimation, respectively. It also had a payback period of 2.95 years and a break-even point at a capacity of 43.16%. In addition, the prepared adsorbent showed significant ability as an inexpensive, reproducible and environmentally friendly compound used in reducing the FFA levels of CPO.

TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids

BackgroundGranulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3β (Akt/GSK3β) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3β signaling pathway in human GCs.MethodsGCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3β signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation.ResultsThe average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3β increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3β level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3β as well as FSHR expression whereas E2 synthesis fell.ConclusionsDuring exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3β pathway in human GCs. This response may contribute to inducing oocyte maturation.

Techno-Economics of Coconut Coir Bio-Adsorbent Utilization on Free Fatty Acid Level Reduction in Crude Palm Oil

The quality of crude palm oil (CPO) is generally determined by the levels of free fatty acids (FFA). This helps in balancing the level of acidity during transportation and storage processes. However, high FFA in CPO is not good for consumer health. One of the methods for absorbing FFA is adsorption, which is the adhesion of atoms, ions, or molecules from a gas, liquid, or dissolved solid to a surface. Therefore, this study aims to analyze the effect of contact time (40, 80 and 120 mins) and Coconut Coir (CC) bio-adsorbent concentrations of 1, 2 and 3 (%, w/v) on the reduction of CPO FFA levels. This began with the activation of CC biochar synthesis by using NaOH and HCl, which produced CC-NaOH and CC-HCl bio-adsorbents based on the product of NaOH. Furthermore, the adsorption process was carried out by mixing CPO with CC-NaOH and CC-HCl bio-adsorbents in a three-necked flask. After this, the filtrate product was obtained and analyzed for its FFA levels. The results showed that the largest percentage reduction for the effect of bio adsorbent concentration was 3% (w/v) at a contact time of 120 mins. It also indicated that this study enabled lower levels of FFA in CPO. Based on the detailed cost estimate, the production cost of the CC-NaOH bio-adsorbent was USD 481,874, sold at USD 95/ton with annual sales and net profit (after tax) at USD 684,000 and USD 141,188, respectively. This profit after tax and rate of return on investment were found to be 20.68 and 39.49% of the entire estimation, respectively. It also had a payback period of 2.95 years and a break-even point at a capacity of 43.16%. In addition, the prepared adsorbent showed significant ability as an inexpensive, reproducible and environmentally friendly compound used in reducing the FFA levels of CPO.

Extraction of Brazil nut kernel oil using green solvents: Effects of the process variables in the oil yield and composition

AbstractThe extraction efficiency of isopropyl alcohol and ethyl alcohol was studied, and the effects of the process variables, static time (St), solvent‐to‐feed (S/F) ratio, and temperature (T) in the oil extraction yield (X0), free fatty acids (FFA) content, total phenolic content (TPC), and β‐sitosterol content were statistically investigated. The amount of solvent used (S/F) did not influence theX0, but St andTsignificantly influenced (p&lt; .05) theX0. The condition that maximized theX0(60.40%) occurred when a St of 9 min and aTof 86°C were used, and low level of FFA were observed in all oils obtained. The process variables studied did not significantly influence (p&gt; .05) in the content of FFA (0.25–0.28%), TPC (29.10–38.47 mg GAE/kg oil), and β‐sitosterol content (9.51–40.32 mg/100 g oil). Its oil is a high source of unsaturated fatty acid. Pressurized liquid extraction is a promising technique for rapid extraction of oil including Brazil nut kernel. Its process recovered 90.58% of oil in 27 min (3 cycles for 9 min of static time).Practical ApplicationsThe optimization of pressurized green solvent extraction has been studied in order to demonstrate that this technology, even employing polar solvents, provides high yields in oil extraction. It is a technology under study that leaves no residue of toxic solvents on vegetable oils. In this study, the use of pressurized liquid extraction with isopropyl alcohol (IPA) and ethyl alcohol (EtOH) as solvents was employed to extract oil from Brazil nut kernel, focusing on the oil rapid recovery as an alternative process to increase the oil yield and improve the use of non‐timber forest product of Amazon biome.

Short-Term Activation of Peroxisome Proliferator-Activated Receptors α and γ Induces Tissue-Specific Effects on Lipid Metabolism and Fatty Acid Composition in Male Wistar Rats.

Dietary fatty acids (FAs) affect certain metabolic routes, including pathways controlled by the peroxisome proliferator-activated receptors (PPARs), but tissue-specific effects are not well-defined. Thus, the aim was to compare the metabolic response in hepatic, adipose, and cardiac tissues after treatment with specific PPAR agonists. Male Wistar rats were randomized into three groups: a control group receiving placebo (n=8); a PPARα agonist group receiving WY-14,643 (n=6); and a PPARγ agonist group receiving rosiglitazone (n=6) for 12 days. All animals received a low-fat standard chow diet and were given a daily dose of placebo or agonist orally. Lipids and FA methyl esters were measured in plasma, liver, and heart and gene expression was measured in liver and adipose tissue, while enzyme activities were measured in liver. Treatment with the PPARα agonist was associated with higher liver mass relative to body weight (liver index), lower plasma, and hepatic total cholesterol, as well as lower plasma carnitine and acylcarnitines, compared with control. In heart, PPARα activation leads to overall lower levels of free FAs and specific changes in certain FAs, compared with control. Furthermore, β-oxidation in liver and the enzymatic activities of well-known PPARα targeted genes were higher following PPARα administration. Overall, rats treated with the PPARα agonist had higher hepatic saturated FAs (SFAs) and monounsaturated FAs (MUFAs) and lower n-6 and n-3 PUFAs, compared to control. Treatment with the PPARγ agonist was associated with a lower liver index, lower plasma triglycerides (TAG) and phospholipids, and higher hepatic phospholipids, compared with control. PPARγ target genes were increased specifically in adipose tissue. Moreover, lower total cardiac FAs and SFA and higher cardiac n-6 PUFA were also associated with PPARγ activation. Altogether, there were characteristic effects of PPARα activation in liver and heart, as well as in plasma. PPARγ effects were not only confined to adipose tissue, but specific effects were also seen in liver, heart, and plasma. In conclusion, short-term treatment with PPAR agonists induced tissue-specific effects on FA composition in liver and heart. Moreover, both PPARα and PPARγ activation lowered plasma TAG and phospholipids, most likely through effects on liver and adipose tissue, respectively. In future studies we aim to reveal whether similar patterns can be found through diet-induced activation of specific pathways.

Plasma levels of free fatty acids correlate with type 2 diabetes mellitus.

Free fatty acids (FFA) mediate adverse metabolic effects such as downregulated carbohydrate metabolisms, providing causal links between obesity and the development of type 2 diabetes mellitus (T2DM). Here, we investigated the plasma concentrations of FFA alone and in combination with protein glycation as potential diagnostic and prognostic biomarkers of T2DM. EDTA-plasma obtained from 48 newly diagnosed male T2DM patients, 48 long-term controlled (24 male and 24 female) T2DM patients, 20 prediabetic male T2DM patients and two age-matched control cohorts (48 non-diabetic (ND) men; 24 male and 24 female ND partipants) were analysed for a set of clinical parameters including FFA. Glycation sites were quantified after tryptic digestion using tandem mass spectrometry. Median plasma concentrations of FFA were almost three-fold higher in samples obtained from newly diagnosed (long-term controlled) T2DM patients than in those obtained from the control group, providing diagnostic sensitivity (SN) of 92% (85%) and specificity (SP) of 90% (88%). When combined with the glycation level of lysine-141 of haptoglobin, diagnostic accuracy improved further for newly diagnosed (SN, 94%; SP 96%) and long-term controlled (SN, 85%; SP, 94%) T2DM patients (HbA1c: SN, 88%; SP, 96%). A prospective pilot study evaluating the prognostic value revealed initially low FFA levels for pre-diabetic patients that increased in the following four years in patients whose prediabetic state worsened or who developed T2DM. FFA levels are elevated in newly diagnosed and long-term controlled T2DM patients, providing high diagnostic accuracy of 87% and 91%, respectively, which improved further when combined with the glycation degree of lysine-141 in haptoglobin. Additionally, FFA showed higher mean fold-changes than HbA1c or FPG in subjects developing T2DM, indicating higher sensitivity towards the progression of the disease.

Comparison of methylation methods for fatty acid analysis of milk fat

Three acid- and alkaline-catalysed transesterification methods were compared with the aim to validate a simple yet reliable protocol for fatty acid (FA) profiling of milk fat. While both the acid- and alkaline-catalysed methods were able to convert completely triglycerides and phospholipids into fatty acid methyl esters (FAMEs), the acid catalyst caused significant degradation of conjugated linoleic acid C18:2c9t11 at high temperature. Although a milder temperature can mitigate this negative impact, a long reaction time (2 h) is required to achieve full methylation. By contrast, despite being unable to methylate free fatty acids (FFA), the alkaline-catalysed transesterification yielded comparable results for all major FA due to the very low level of FFA in milk. The alkaline-catalysed methylation is benign for C18:2c9t11. We recommend here a simple one-step protocol based on 0.2 M methanolic KOH, a short reaction time (20 min) and a mild reaction temperature (50 °C) for milk FAME preparation.

Browning deficiency and low mobilization of fatty acids in gonadal white adipose tissue leads to decreased cold-tolerance of transglutaminase 2 knock-out mice

During cold-exposure ‘beige’ adipocytes with increased mitochondrial content are activated in white adipose tissue (WAT). These cells, similarly to brown adipose tissue (BAT), dissipate stored chemical energy in the form of heat with the help of uncoupling protein 1 (UCP1). We investigated the effect of tissue transglutaminase (TG2) ablation on the function of ATs in mice. Although TG2+/+ and TG2−/− mice had the same amount of WAT and BAT, we found that TG2+/+ animals could tolerate acute cold exposure for 4h, whereas TG2−/− mice only for 3h. Both TG2−/− and TG2+/+ animals used up half of the triacylglycerol content of subcutaneous WAT (SCAT) after 3h treatment; however, TG2−/− mice still possessed markedly whiter and higher amount of gonadal WAT (GONAT) as reflected in the larger size of adipocytes and lower free fatty acid levels in serum. Furthermore, lower expression of ‘beige’ marker genes such as UCP1, TBX1 and TNFRFS9 was observed after cold exposure in GONAT of TG2−/− mice, paralleled with a lower level of UCP1 protein and a decreased mitochondrial content. The detected changes in gene expression of Resistin and Adiponectin did not provoke glucose intolerance in the investigated TG2−/− mice, and TG2 deletion did not influence adrenaline, noradrenaline, glucagon and insulin production. Our data suggest that TG2 has a tissue-specific role in GONAT function and browning, which becomes apparent under acute cold exposure.

Effect of APOE ε4 Genotype on Metabolic Biomarkers in Aging and Alzheimer's Disease.

Alzheimer's disease (AD) may have heterogeneous pathophysiological underpinnings, with risk factors including apolipoprotein rmvarep4 (APOE4) genotype and insulin resistance. We hypothesized that distinct phenotypes exist within AD. We examined APOE4 and metabolic biomarkers in 338 subjects (n = 213 nondemented (ND), n = 125 AD). We further characterized steady state free fatty acid (FFA) levels in a subset of 45 participants who had also participated in a hyperinsulinemic-euglycemic clamp. Insulin resistance (HOMA-IR) was elevated in AD versus ND (p = 0.04) and in APOE4 noncarriers versus carriers (p < 0.01). This was driven by increased fasting insulin in AD versus ND (p < 0.01) and in APOE4 non-carriers versus carriers (p = 0.01). Fasting glucose was not different. In subjects who underwent a clamp, there was a group x genotype interaction on FFA levels during hyperinsulinemia (p = 0.03). APOE4 non-carriers with AD had higher FFA levels, while APOE4 carriers with AD exhibited lower FFA levels. Metabolic dysfunction is overrepresented in individuals with AD dementia who do not carry the APOE4 allele. This suggests that important subsets of AD phenotypes may exist that diverge metabolically.

Effect of fat and salt reduction on the changes in the concentrations of free amino acids and free fatty acids in Cheddar-style cheeses during maturation

The study investigated the effects of reducing fat content from 33 (full-fat, FF) to 22 (reduced-fat, RF) or 16 (half-fat, HF) % on the concentrations of total and individual free amino acids (FAA) and free fatty acids (FFA) in Cheddar-style cheeses with 1.9 (full-salt, FS), 1.2 (reduced-salt, RS) or 0.9 (half-salt, HS) % NaCl over a 270d maturation period at 8°C. Both FAA and FFA increased continuously during ripening, from ∼1200 and 230mg/kg at 30d to 5500 and 1593mg/kg, respectively, in FFFS at 270d. Reducing fat content resulted in higher concentrations of FAA (e.g., from 5500mg/kg in FFFS to 6400mg/kg in HFFS at 270d) and lower levels of FFA (e.g., from 1593mg/kg in FFFS to 1140mg/kg in the HFFS cheese at 270d). Reducing salt content from 1.9 to 1.2 or 0.9 % resulted in a significant decrease in FAA in the FF cheese, from 5500mg/kg in FFFS to 4000mg/kg in FFHS at 270d. Salt content did not significantly affect the concentration of FAA in RF or HF cheeses, or the concentration of total or individual FFA in the FF, RF or HF cheeses.

Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice.

Jiang Tang Xiao Ke (JTXK) granule, a Chinese herbal formula, has been used clinically to treat type 2 diabetes (T2DM) for decades. Our previous studies showed that JTXK granule exhibited anti-diabetic and anti-oxidative functions in experimental diabetic rats induced by a high fat diet and streptozotocin. However, the underlying mechanisms remain poorly understood. Herein, we aimed to investigate the therapeutic effect of JTXK granule on T2DM KKAy mice and the possible associations with skeletal muscle in the current study. Our results showed that JTXK granule significantly reduced food intake and body weight in T2DM KKAy mice. JTXK granule treatment also decreased the blood glucose and HbA1c levels and increased the insulin sensitivity in a time-dependent manner. Additionally, it ameliorated hyperlipidaemia and induced a lower free fatty acid level, displaying an effect on disorders of lipid metabolism. JTXK granule significantly increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/Akt) and glucose transporter 4 (Glut4) and decreased the expression of glycogen synthase kinase 3β (GSK3β). We concluded that JTXK granule is an effective drug for T2DM through regulating the PI3K/Akt signalling pathway in skeletal muscle.

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.

Biomarkers of Insulin for the Diagnosis of Hyperinsulinemic Hypoglycemia in Infants and Children

To evaluate thresholds of various biomarkers for defining excess insulin activity to recognize congenital hyperinsulinism. This was a retrospective chart review of diagnostic fasting tests in children with ketotic hypoglycemia (n=30) and genetically/pathology confirmed congenital hyperinsulinism (n=28). Sensitivity and specificity for congenital hyperinsulinism were determined for plasma insulin, β-hydroxybutyrate, free fatty acids (FFA), C-peptide, insulin-like growth factor binding protein-1 (IGFBP-1), and the glycemic response to glucagon (through the glucagon stimulation test [GST]) at the time of hypoglycemia. Only 23 of the 28 subjects with congenital hyperinsulinism had detectable insulin (median, 6.7 μIU/mL), and insulin was undetectable in all subjects with ketotic hypoglycemia. Compared with ketotic hypoglycemia, subjects with congenital hyperinsulinism had higher GST values (57 vs 13mg/dL; ΔGST ≥30mg/dL in 24 of 27 subjects with congenital hyperinsulinism vs 0 of 30 subjects with ketotic hypoglycemia) and C-peptide levels (1.55 vs 0.11ng/mL), with lower levels of FFA (0.82 vs 2.51mM) and IGFBP-1 (59.5 vs 634ng/mL). At the time of hypoglycemia, the upper limits of β-hydroxybutyrate and FFA in subjects with congenital hyperinsulinism were higher than reported previously (β-hydroxybutyrate <1.8mM and FFA <1.7mM), providing the best sensitivity for congenital hyperinsulinism vs ketotic hypoglycemia. A C-peptide level ≥0.5ng/mL was 89% sensitive and 100% specific, and an IGFBP-1 level ≤110ng/mL was 85% sensitive and 96.6% specific. Because low or undetectable insulin level during hypoglycemia does not exclude the diagnosis of hyperinsulinism, C-peptide and IGFBP-1 may inform the diagnosis of congenital hyperinsulinism. In this group of children with well-defined congenital hyperinsulinism, thresholds for "suppressed" β-hydroxybutyrate and FFA are higher than previously reported levels.

The effects of packaging type on the quality characteristics of fresh raw pistachios (Pistacia vera L.) during the storage

In this study, the effect of different packaging systems on physicochemical, microbiological, aroma, color and sensory characteristics of fresh raw pistachios during storage was evaluated. Fresh raw pistachios were stored at vacuum (VP), modified atmosphere (MAP) and conventional packaging (CP) at 4 °C for 30 days. Total mesophilic bacteria (TMAB) counts and free fatty acids (FFA) values were the most discriminating parameters. At the end of the storage, FFA level and TMAB population of the samples stored in the CP were the highest while VP and MAP enabled lower levels of FFA and TMAB, respectively. During the storage palmitic acid content increased whereas linoleic acid level decreased in the all types of packaging. No significant differences were found in other fatty acids during storage. Sensory analysis showed variable results among the three packaging systems. In conclusion, the use of MAP was generally recommended for the maintenance of quality of fresh raw pistachio for longer storage periods.

The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice.

BackgroundThe hallmark of Type 2 diabetes (T2D) is hyperglycemia, although there are multiple other metabolic abnormalities that occur with T2D, including insulin resistance and dyslipidemia. To advance T2D prevention and develop targeted therapies for its treatment, a greater understanding of the alterations in metabolic tissues associated with T2D is necessary. The aim of this study was to use microarray analysis of gene expression in metabolic tissues from a mouse model of pre-diabetes and T2D to further understand the metabolic abnormalities that may contribute to T2D. We also aimed to uncover the novel genes and pathways regulated by the insulin sensitizing agent (CL-316,243) to identify key pathways and target genes in metabolic tissues that can reverse the diabetic phenotype.MethodsMale MKR mice on an FVB/n background and age matched wild-type (WT) FVB/n mice were used in all experiments. Skeletal muscle, liver and fat were isolated from prediabetic (3 week old) and diabetic (8 week old) MKR mice. Male MKR mice were treated with CL-316,243. Skeletal muscle, liver and fat were isolated after the treatment period. RNA was isolated from the metabolic tissues and subjected to microarray and KEGG database analysis.ResultsSignificant decreases in the expression of mitochondrial and peroxisomal fatty acid oxidation genes were found in the skeletal muscle and adipose tissue of adult MKR mice, and the liver of pre-diabetic MKR mice, compared to WT controls. After treatment with CL-316,243, the circulating glucose and insulin concentrations in the MKR mice improved, an increase in the expression of peroxisomal fatty acid oxidation genes was observed in addition to a decrease in the expression of retinaldehyde dehydrogenases. These genes were not previously known to be regulated by CL-316,243 treatment.ConclusionsThis study uncovers novel genes that may contribute to pharmacological reversal of insulin resistance and T2D and may be targets for treatment. In addition, it explains the lower free fatty acid levels in MKR mice after treatment with CL-316,243 and furthermore, it provides biomarker genes such as ACAA1 and HSD17b4 which could be further probed in a future study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0003-8) contains supplementary material, which is available to authorized users.