Serum Free Fatty Acid Concentrations Research Articles

Serum Free Fatty Acid Concentration Predicts ARDS after Off-Pump CABG: A Prospective Observational Study.

Free fatty acids (FFAs) are established risk factors for various cardiovascular and metabolic disorders. Elevated FFAs can trigger inflammatory response, which may be associated with the occurrence of acute respiratory distress syndrome (ARDS) in cardiac surgery. In this prospective study, we aimed to investigate the association between circulating FFA and the incidence of ARDS, as well as the length of ICU stay, in patients undergoing off-pump coronary artery bypass grafting (CABG). We conducted a single-center, prospective, observational study among patients undergoing off-pump CABG. The primary endpoint was the occurrence of ARDS within 6days after off-pump CABG. Serum FFA were measured at baseline and 24h post-procedure, and the difference (Δ-FFA) was calculated. A total of 180 patients were included in the primary analysis. The median FFA was 2.3mmol/L (quartile 1 [Q1]-Q3, 1.4-3.2) at baseline and 1.5mmol/L (Q1-Q3, 0.9-2.3) 24h after CABG, with a Δ-FFA of 0.6mmol/L (Q1-Q3, -0.1 to 1.6). Patients with elevated Δ-FFA levels had a significantly higher ARDS occurrence (55.6% vs. 22.2%; P < 0.001). Elevated Δ-FFA after off-pump CABG correlated with a significantly lower PaO2/FiO2 ratio, prolonged mechanical ventilation, and extended length of ICU stay. The area under the curve (AUC) of Δ-FFA for predicting ARDS (AUC, 0.758; 95% confidence interval, 0.686-0.831) significantly exceeded the AUC of postoperative FFA (AUC, 0.708; 95% CI 0.628-0.788; P < 0.001). Elevated Δ-FFA levels correlated with ARDS following off-pump CABG. Monitoring FFA may assist in identifying high-risk patients for ARDS, facilitating timely interventions to improve clinical outcomes.

4,4-Diallyl curcumin bis(2,2-hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine-choline-deficient diet and Western diet mouse models.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20. Among these proteins, the upregulated expression of CPT-I was most prominent. CPT-I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial β-oxidation of fatty acids. Given recent research showing that CPT-I activation could be a viable pathway for NASH treatment, we hypothesized that 35e could serve as a potential agent for treating NASH. The efficacy of 35e in treating NASH was evaluated in methionine- and choline-deficient (MCD) diet- and Western diet (WD)-induced models that mimic human NASH. In the MCD diet-induced model, both short-term (2 weeks) and long-term (7 weeks) treatment with 35e effectively regulated elevated serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of 35e was obtained only in the short-term treatment group. As a comparative compound in the MCD diet-induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride/total cholesterol, serum ALT/AST, or hepatic steatosis. In the WD-induced model, 35e ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that 35e may promote lipid metabolism or impede lipid accumulation. Overall, 35e displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT-I upregulation could further underscore their efficacy as anti-NASH agents.

Caffeic acid combined with arabinoxylan or β-glucan attenuates diet-induced obesity in mice via modulation of gut microbiota and metabolites

Polyphenols and dietary fibers in whole grains are important bioactive compounds to reduce risks for obesity. However, whether the combination of the two components exhibits a stronger anti-obesity effect remains unclear. Caffeic acid is a major phenolic acid in cereals, and arabinoxylan and β-glucan are biological macromolecules with numerous health benefits. Here, we investigated the effect of caffeic acid combined with arabinoxylan or β-glucan on glucose and lipid metabolism, gut microbiota, and metabolites in mice fed a high-fat diet (HFD). Caffeic acid combined with arabinoxylan or β-glucan significantly reduced the body weight, blood glucose, and serum free fatty acid concentrations. Caffeic acid combined with β-glucan effectively decreased serum total cholesterol levels and hepatic lipid accumulation, modulated oxidative and inflammatory stress, and improved gut barrier function. Compared with arabinoxylan, β-glucan, and caffeic acid alone, caffeic acid combined with arabinoxylan or β-glucan exhibited a better capacity to modulate gut microbiota, including increased microbial diversity, reduced Firmicutes/Bacteroidetes ratio, and increased abundance of beneficial bacteria such as Bifidobacterium. Furthermore, caffeic acid combined with β-glucan reversed HFD-induced changes in microbiota-derived metabolites involving tryptophan, purine, and bile acid metabolism. Thus, caffeic acid and β-glucan had a synergistic anti-obesity effect by regulating specific gut microbiota and metabolites.

High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

Effects of the menstrual cycle on EPOC and fat oxidation after low-volume high-intensity interval training.

Low-volume high-intensity interval training (HIIT) for weight loss has become prevalent in recent years, with increased excess post-exercise oxygen consumption (EPOC) as the mechanism. However, the influence of the menstrual cycle on EPOC and fat oxidation following low-volume HIIT is unclear. This study aimed to investigate the effect of the menstrual cycle on the increase in EPOC and fat oxidation after low-volume HIIT. Twelve eumenorrheic women participated during their early follicular and luteal phases. On each experimental day, they performed low-volume HIIT comprising fifteen repeated 8 s sprint cycling tests with 12 s rests, for 5 min. Expired gas samples were collected before and every 60 min until 180 min post-exercise. EPOC was defined as the increase in oxygen consumption from the resting state, and the total EPOC and fat oxidation were calculated from the total time of each measurement. Blood samples for serum estradiol, progesterone, free fatty acids, blood glucose, lactate, and plasma noradrenaline were collected and assessed before immediately after, and at 180 min post-exercise and were assessed. Serum estradiol and progesterone were significantly higher in the luteal phase than the follicular phase (P<0.01 for both). No significant differences in total EPOC and fat oxidation were found between the menstrual phases. Serum free fatty acid, blood glucose, lactate, and plasma noradrenaline concentrations were not affected by the menstrual cycle. These results suggest that the menstrual cycle does not affect the increase in EPOC or fat oxidation after low-volume HIIT.

Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice

ObjectivesAcute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. MethodsLean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. ResultsIn the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480– was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. ConclusionsThese data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.

Role of serum free fatty acids in determining severity of diabetic nephropathy: A case control study

Introduction and Aim: The Diabetic Nephropathy (DN) is a result of impaired renal function in Type 2 diabetes. At the onset of diabetes, microvascular complication increases due to accumulation of free fatty acids (FFA) causing renal damage. A study was conducted to estimate the concentration of serum FFA causing severity of diabetic nephropathy.&#x0D; &#x0D; Materials and Methods: 90 Type 2 diabetic subjects and 30 study controls (age group 35 to 65 years) were selected from the medicine OPD of S N Medical College and HSK Hospital, Bagalkot. Based on the presence of microalbuminuria, the 90 Type 2 diabetic patients were equally divided in to 3 groups, named as stage I to stage III. The serum FFA was estimated by ELISA method in these three groups and control subjects. The statistical analysis was done using SPSS software version 19 utilizing unpaired “t” test for quantitative data and Pearson’s correlation tests.&#x0D; &#x0D; Results: The estimated serum FFA levels in stage I to III was found to be higher and highly significant as compared to control (p=0.001). We find the best cut off value of serum FFA was 4.75 mmol/L, causing severity of diabetic nephropathy. The area under the curve (AUC) is 0.92 with the specificity of 86%, sensitivity 89% and the diagnostic accuracy was found to be of 87%.&#x0D; &#x0D; Conclusion: Serum free fatty acid levels were higher in diabetic nephropathy subjects, which could be used as diagnostic marker for the severity of renal damage with cut off value of 4.75 mmol/L.

Free fatty acids induce coronary microvascular dysfunction via inhibition of the AMPK/KLF2/eNOS signaling pathway.

Increased levels of serum free fatty acids (FFAs) are closely associated with microvascular dysfunction. In our previous study, a coronary microvascular dysfunction (CMD) model was successfully established via lipid infusion to increase the levels of serum FFAs in mice. However, the underlying mechanisms remained poorly understood. Therefore, the aim of the present study was to explore the mechanism underlying FFA‑induced CMD. A CMD mouse model was established via lipid combined with heparin infusion for 6h to increase the concentration of serum FFAs. Following the establishment of the model, the coronary flow reserve (CFR), extent of leukocyte activation and cardiac microvascular structures were assessed in the mice. Cardiac microvascular endothelial cells (CMECs) were treated with different concentrations of palmitic acid and cell viability was evaluated. Changes in the expression levels of AMP‑activated protein kinase (AMPK), Krüppel‑like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS) were identified by immunohistochemical and western blot analyses. Experiments using AMPK activator, KLF2 overexpression plasmid, small interfering RNAs and nicorandil were subsequently designed to investigate the potential involvement of the AMPK/KLF2/eNOS signaling pathway. These experiments revealed that FFAs could induce CMD in mice, which was characterized by reduced CFR (1.89±0.37 vs. 2.74±0.30) and increased leukocyte adhesion (4,350±1,057.5 vs. 11.8±5.4cells/mm2) compared with the control mice. CD11b expression and intracellular reactive oxygen species (ROS) levels were increased in CMD model mice compared with control mice. Serum TNF‑α and IL‑6 levels were higher in the model group than in the control group. Transmission electron microscopy revealed that CMECs in heart tissues of model mice were severely swollen. In addition, palmitic acid decreased CMEC viability and increased ROS production in a dose‑dependent manner. Notably, the AMPK/KLF2/eNOS signaling pathway was demonstrated to be suppressed by FFAs both invivo and invitro. Activation of this axis with AMPK activator, KLF2 overexpression plasmid or nicorandil restored the CFR in CMD model mice, inhibited oxidative stress and increased CMEC viability. Taken together, the results of the present study demonstrated that FFAs could induce CMD via inhibition of the AMPK/KLF2/eNOS signaling pathway, whereas activation of this pathway led to the alleviation of FFA‑induced CMD, which may be a therapeutic option for CMD.

Chronic unpredictable mild stress promotes atherosclerosis via adipose tissue dysfunction in ApoE-/- mice.

Chronic unpredictable mild stress (CUMS) has been shown to exacerbate atherosclerosis, but the underlying mechanism remains unknown. Adipose tissue is an energy storage organ and the largest endocrine organ in the human body, playing a key role in the development of cardiovascular disease. In this research, it was hypothesized that CUMS may exacerbate the development of atherosclerosis by inducing the hypertrophy and dysfunction of white adipocytes. The CUMS-induced atherosclerosis model was developed in Western diet-fed apolipoprotein E (ApoE)-/- mice. White adipose tissue (WAT), serum, aortic root, and the brachiocephalic trunk were collected and tested after 12 weeks of CUMS development. The mouse model of CUMS was evaluated for depression-like behavior using the open field test (OFT) and the elevated plus maze (EPM) test. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect serum noradrenaline and urine adrenaline protein levels. Serological assays were used to detect serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and free fatty acid (FFA) concentrations. Hematoxylin and eosin (H&E) staining and oil red O were used to detect atherosclerotic plaque area, lipid deposition, and adipocyte size. The mRNA levels of genes related to aberrant adipose tissue function were determined using real-time PCR. Immunofluorescence assay and western blotting were conducted to examine the expression of proteins in the adipose tissue samples. CUMS aggravated vascular atherosclerotic lesions in ApoE-/- mice. It decreased body weight while increasing the percentage of WAT. The serological results indicated that the concentration of HDL decreased in CUMS mice. Notably, adipocyte hypertrophy increased, whereas the mRNA levels of Pparg and its target genes (Slc2a4 (encodes for GLUT4), Adipoq, and Plin1) decreased. Further investigation revealed that CUMS increased subcutaneous inguinal WAT (iWAT) lipid synthesis and adipocyte inflammation while decreasing lipid hydrolysis and the expression of HDL-associated protein ApoA-I. Moreover, CUMS aggravated insulin resistance in mice and inhibited the insulin pathway in iWAT. These findings indicated that CUMS induces adipose tissue dysfunction via a mechanism that leads to dyslipidemia, increased inflammation, and insulin resistance in the body, thereby exacerbating atherosclerosis. Notably, CUMS that is involved in decreasing the expression of HDL-associated proteins in adipose tissue may be a crucial link between adipose hypertrophy and advanced atherosclerosis. This study reveals a novel mechanism via which CUMS exacerbates atherosclerosis from the novel perspective of abnormal adipose function and identifies a novel potential therapeutic target for this disease.

Certain sulfonylurea drugs increase serum free fatty acid in diabetic patients: A systematic review and meta-analysis.

BACKGROUNDSulfonylurea (SU) is a commonly used antidiabetic drugs effective for type 2 diabetes mellitus. Previous studies have reported that the SU treatment could alter the serum free fatty acid (FFA) concentration in diabetic patients; however, their exact effects remain unknown.AIMTo assess the impact of SU on the FFA level in diabetic patients.METHODSA systematic literature search was conducted by consulting the PubMed, EMBASE, Cochrane Library, Reference Citation Analysis (https://www.referencecitationanalysis.com/), and Web of Science databases from January 1, 1991 to July 30, 2021. Either a fixed-effects model or random-effects model was applied to study the association between SU treatment and FFA concentration according to the heterogeneity test. Two investigators independently performed data extraction. The mean difference (MD) and corresponding 95% confidence interval (CI) were used to measure effect size. R3.5.1 software was utilized for conducting statistical analyses.RESULTSA total of 13 studies with 2273 individuals were selected. Results indicated that FFA concentration increased slightly after treatment with SU (MD = 0.08, 95%CI: 0.03-0.12, P < 0.01). In addition, we found that SU treatment combined with other antidiabetics could also increase the concentration of serum FFA (MD = 0.14, 95%CI: 0.01-0.28, P < 0.01). Regarding the type of SU, there was no significant difference in FFA concentration with glimepiride or glibenclamide. FFA concentration was higher at ≥ 12 wk (MD = 0.09, 95%CI: 0.04-0.13) but not at < 12 wk (MD = 0.01, 95%CI: -0.07-0.09).CONCLUSIONSU treatment could increase the serum FFA concentration in diabetic patients. The fundamental underlying mechanism still needs further investigation.

Effect of Chinese Herbs on Serum Biochemical Parameters, Immunity Indices, Antioxidant Capacity and Metabolomics in Early Weaned Yak Calves.

Simple SummaryHerbs, as supplementary feed, have shown positive effects on livestock. The yak is a unique animal on the Qinghai-Tibetan plateau, and plays important roles in local livelihoods and ecology. Because of the harsh climate conditions, early weaned yak calves often face environmental and nutritional stress. The herbal active ingredients of some herbs improve the antioxidant capacity and immunity of animals. In the current study, early-weaned yak calves were supplemented with three widely used Chinese traditional herbal root extracts to examine whether they can improve the immune response and antioxidant capacity. The results demonstrated that the supplementary herbs increased the serum antioxidant capacity, and improved the energy and nitrogen metabolism of the yak calves.Chinese traditional herbs are used widely as feed supplements to improve the immune response and antioxidant capacity of livestock. Twenty early-weaned 4-month-old yak calves (72.3 ± 3.65 kg) were divided randomly into four groups (n = 5 per group); three groups were provided with supplementary 80 mL/kg DMI of the root water extracts of either Angelica sinensis, Codonopsis pilosula or Glycyrrhiza uralensis, and one group (control) was not provided with a supplement. Compared to control calves, calves consuming the three herbal extracts increased serum concentrations of albumin (ALB) and glutathione peroxidase (GSH-Px), but decreased serum concentrations of free fatty acids (FFAs) and malondialdehyde (MDA) (p < 0.05). Calves consuming A. sinensis decreased (p < 0.05) serum concentration of total cholesterol (TC), and increased (p < 0.05) serum concentration of total proteins (TP). Serum FFA concentrations increased (p = 0.004) linearly with time in the control group, but not in the groups consuming herbs. Serum metabolomic data demonstrated that A. sinensis and C. pilosula regulate mainly amino acid metabolism, while G. uralensis regulates mainly carbon and amino acid metabolism. It was concluded that the three herbal root extracts, as dietary supplements, improved energy and nitrogen metabolism, and enhanced the antioxidant capacity of yak calves.

Impaired autophagy aggravates oxidative stress in mammary gland of dairy cows with clinical ketosis

When ketosis occurs, supraphysiological levels of free fatty acids (FFA) can cause oxidative injury to the mammary gland and autophagy can regulate the cellular oxidative status. The aim of this study was to investigate the autophagy status of mammary tissue and its associations with oxidative stress in healthy and clinically ketotic dairy cows. Mammary tissue and blood samples were collected from healthy cows [n = 15, β-hydroxybutyrate (BHB) <0.6 mM] and clinically ketotic cows (n = 15, BHB >3.0 mM) at 3 to 15 (average = 7) days in milk. For in vitro study, bovine mammary epithelial cells (BMEC) isolated from healthy cows were treated with 0, 0.3, 0.6, or 1.2 mM FFA for 24 h. Furthermore, BMEC were pretreated with 100 nM rapamycin, an autophagy activator, for 4 h or 50 mM 3-methyladenine (3-MA), an autophagy inhibitor, for 1 h, followed by treatment with or without FFA (1.2 mM) for another 24 h. Oxidation indicators and autophagy-related protein abundance were measured. Compared with healthy cows, serum concentrations of FFA, BHB, and malondialdehyde were greater in clinically ketotic cows, but milk production (kg/d), milk protein (kg/d), activities of superoxide dismutase, catalase, and glutathione peroxidase were lower. Abundances of mRNA and protein of autophagy-related gene 5 (ATG5) and 7 (ATG7) were lower, but sequestosome-1 (SQSTM1, also called p62) greater in mammary tissue of clinically ketotic cows. The mRNA abundance of microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3) and protein abundance of LC3-II were lower in mammary tissue of clinically ketotic cows. In vitro, exogenous FFA increased the content of malondialdehyde and reactive oxygen species, but decreased the activities of superoxide dismutase, catalase, and plasma glutathione peroxidase. Compared with the 0 mM FFA group, abundance of ATG5, ATG7, LC3-II was greater, but p62 was lower in the 0.6 mM FFA-treated cells. Similarly, abundance of ATG5, ATG7, and LC3-II was lower, but p62 greater in the 1.2 mM FFA-treated cells relative to 0 mM FFA group. Culture with rapamycin alleviated oxidative stress induced by 1.2 mM FFA, whereas 3-MA aggravated it. Overall, results indicated that a low concentration (0.6 mM) of FFA can induce oxidative stress and activate autophagy in BMEC. At higher concentrations of FFA (1.2 mM), autophagy is impaired and oxidative stress is aggravated. Autophagy is a mechanism for BMEC to counteract FFA-induced stress. As such, it could serve as a potential target for further development of novel strategies against oxidative stress.

Antiobesity and Hepatoprotective Effects of Protein Hydrolysates Derived from Protaetia brevitarsis in an Obese Mouse Model.

Background Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. Methods For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(–)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. Results The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(–) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(–) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, β3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. Conclusions Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.

Serum free fatty acid levels and insulin resistance in patients undergoing one-anastomosis gastric bypass

IntroductionOne anastomosis gastric bypass (OAGB) leads to improvement in glucose homeostasis; however, the mechanism of this beneficial effect is not fully understood. Increased serum free fatty acid (FFA) concentrations in obese subjects contribute to the development of insulin resistance and type 2 diabetes.AimThe authors hypothesized that improvement in glucose homeostasis after OAGB may be associated with a decrease in FFA concentration.Material and methodsSerum FFA levels were measured by gas chromatography-mass spectrometry before and 3 months after OAGB and, for comparison, in patients who underwent laparoscopic sleeve gastrectomy (LSG). Serum insulin was assayed by immunoenzymatic method, and other parameters by standard laboratory methods.ResultsOAGB resulted in a large decrease in FFA levels and great improvement in insulin sensitivity. These effects in patients after LSG were less prominent.ConclusionsResults suggest that decreased serum FFA levels after OAGB contribute to resolution of insulin sensitivity after this type of bariatric surgery.

The Effect of L-Carnitine, Green Tea Extract and Lotus Leaf Extract on the Body Fat Percentage in High Energy Diet-Induced Obese Rats

Background Obesity has become a public health issue of global concern. Obesity is often associated with the occurrence of many diseases, and will also increase mortality; it not only affects personal health, but also increases healthcare costs, thus reducing social productivity and causing negative social and economic impacts. Therefore, ameliorating obesity is an issue worth attention and effort. The development of a natural and safe anti-obesity combination is worthy of further research. It is known that L-carnitine, green tea and lotus leaves have anti-obesity potential, but there is no research and discussion on this novel combination to improve body fat. Objective This study explored how the dietary supplement formula containing L-carnitine, green tea extract and lotus leaf extract (CGL) lowered the body fat accumulation in rats induced by high-energy diet. Design The test used 60-week-old male Sprague Dawley® white rats, which were first divided into the control group (12 rats were given normal feed) and the experimental group (48 rats were given high energy diet; HE). The HE group was further divided into H2O and CGL groups (296, 593 and 1186 mg/kg, to be designated as CGL-L, CGL-M, CGL-H respectively). The rats were first fed with feed for five-weeks, and then fed with different doses of CGL by gavage starting from the sixth-week. After nine-weeks of feeding, the rats were sacrificed to obtain their body weight, feed intake, body fat, serum biochemical indices and liver lipid measurements. Results The results show that the final body weight of HE+CGL-L (578.8±41.6 g) was significantly lower than that of HE+H2O (634.9±42.2 g), and the body fat amount of HE+CGL-L (36.6±9.8 g) was significantly lower than that of HE+H2O (49.4±13.8 g). Feed efficiency and calorie efficiency of HE+CGL-L were also significantly lower than that of HE+H2O (p&lt;0.001). HE+CGL-M and HE+CGL-H were also able to significantly reduce the final body weight, body fat amount and serum-free fatty acid concentration (p&lt;0.05). Conclusion CGL can significantly reduce the final body weight, body fat amount, body fat ratio, feed efficiency and calorie efficiency. CGL has the potential as a new dietary supplement for weight loss. However, the significance of these results on humans taking the supplement for prolonged periods of time is unknown and should be a focus for future investigations.

Aquaporin 7\u2002involved in GINSENOSIDE-RB1-mediated anti-obesity via peroxisome proliferator-activated receptor gamma pathway

BackgroundObesity, characterized by the excessive accumulation of triglycerides in adipocytes and their decreased excretion from adipocytes, is closely related to various health problems. Ginsenoside Rb1 (Rb1), the most active component of the traditional Chinese medicine ginseng, has been reported to have positive effects on lipid metabolism. The aim of the present study was to determine the protective effects of Rb1 on glycolipid metabolism under obesity conditions and its mechanisms and to reveal the signaling pathways involved.MethodsIn our study, male C57BL/6 mice with obesity induced by a high-fat diet (HFD) and mature 3 T3-L1 adipocytes were used to investigate the role of Rb1 in lipid accumulation and explore its possible molecular mechanism in vivo and in vitro, respectively.ResultsRb1 reduced the body weight, fat mass, adipocytes size and serum free fatty acid (FFA) concentration of obese mice. In differentiated 3 T3-L1 adipocytes, Rb1 reduced the accumulation of lipid droplets and stimulated output of triglycerides. Additionally, the expression of peroxisome proliferator-activated receptor gamma (PPARγ), phosphorylated PPARγ (Ser112) and aquaporin 7 (AQP7) was upregulated in adipocytes and adipose tissues upon Rb1 treatment. However, intervention of GW9662, PPARγ antagonist, attenuated Rb1-mediated effects on glycolipid metabolism and AQP7 levels.ConclusionsThese data indicated that Rb1 reduced body weight and improved glycolipid metabolism by upregulating PPARγ and AQP7 protein levels. Our study indicated a potential role for Rb1 in the prevention and treatment of obesity.

2268-PUB: Relationship between Serum Free Fatty Acid and Proinsulin Concentrations

Background: The causes of pancreatic beta-cell dysfunction include glucose toxicity and lipotoxicity. Basic research has suggested that free fatty acids (FFAs) damage pancreatic beta-cells. However, the relationship between FFAs and pancreatic beta-cell dysfunction has not been clarified in humans. Therefore, we investigated the relationship between the serum concentrations of FFA and proinsulin (PI), a marker of pancreatic beta-cell dysfunction, in a general Japanese population. Methods: This was a cross-sectional study of 489 people (226 men, 263 women; age 35-79 years) from a rural community in Hokkaido, Japan who were not taking diabetic medication and who provided fasting blood samples. Serum PI was measured by a radioimmunoassay, and was compared among quartiles defined with respect to FFA concentration. Because the serum FFA and PI levels showed skewed distributions, univariable and multivariable regression analyses were performed after logarithmic transformation. Results: PI, age, body mass index, and fasting blood glucose and insulin were positively associated with serum FFA quartile: for PI, median (first quartile, third quartile): Q1 8.1 (6.0, 11.7), Q2 8.5 (6.9, 13.1), Q3 9.2 (6.7, 14.5), and Q4 11.2 (7.6, 16.7); p&amp;lt;0.01. Univariable regression analysis showed that ln(FFA) was positively associated with ln(PI) (partial regression coefficient: 0.19, 95% confidence interval (CI): 0.07, 0.31, p&amp;lt;0.01). This positive association remained after adjustment for age and sex (partial regression coefficient: 0.19, 95% CI: 0.07, 0.31, p&amp;lt;0.01), and also after adjustment for age, sex, and HbA1c (partial regression coefficient: 0.12, 95% CI: 0.01, 0.23, p&amp;lt;0.05). Conclusion: Serum FFA was positively associated with PI in a general Japanese population. Thus, FFA may play a role in pancreatic beta-cell dysfunction. Disclosure K. Chiba: None. A. Nakamura: None. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Ukawa: None. K. Nakamura: None. T. Nakagawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk A/S, Sanofi. Consultant; Self; Astellas Pharma Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Medscape, Medtronic, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. A. Tamakoshi: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd.

Effect of High Fructose-Induced Metabolic Syndrome on Tissue Vitamin E and Lipid Peroxide Levels in Rats.

In the present study, we examined the effect of high fructose-induced metabolic syndrome (MetS) on tissue vitamin E and lipid peroxide (LPO) levels in rats. Feeding of a diet containing 60% fructose (HFD) to Wistar rats for 2, 4, and 6 wk caused week-dependent increases in HOMA-IR score and serum insulin, triglyceride, total cholesterol, and free fatty acid concentrations. Each week HFD feeding increased serum vitamin E concentration. Six-week HFD feeding reduced vitamin E status (the serum ratio of vitamin E/triglyceride+total cholesterol). Four- and 6-wk HFD feeding increased serum LPO concentration. Two-week HFD feeding increased liver, heart, kidney, and skeletal muscle (SM) vitamin E contents and decreased white adipose tissue (WAT) vitamin E content. Four- and 6-wk HFD feeding further reduced WAT vitamin E content without affecting the increased kidney and SM vitamin E contents. Six-week HFD feeding reduced the increased liver and heart vitamin E contents below the level of non-HFD feeding. Four-week HFD feeding increased heart and WAT LPO contents. Six-week HFD feeding increased liver LPO content and further increased heart and WAT LPO contents. Kidney and SM LPO contents remained unchanged. These results indicate that HFD-rats with early MetS have increased liver, kidney, heart, and SM vitamin E contents and decreased WAT vitamin E content under unchanged tissue LPO content and vitamin E status, while HFD-fed rats with progressed MetS have both decreased liver, heart, and WAT vitamin E contents under increased tissue LPO content and disrupted vitamin E status.

Acute Voluntary Wheel Running Attenuates Olanzapine‐Induced Hyperglycemia in Male Mice

BackgroundOlanzapine is a second‐generation antipsychotic often used in the treatment of schizophrenia and other “off‐label” conditions. Though effective in reducing psychoses, the use of olanzapine is associated with adverse metabolic side effects. Acutely, olanzapine increases liver glucose output and the development of insulin resistance. Chronic olanzapine treatment leads to weight gain and predisposes individuals to the development of cardiovascular disease and type 2 diabetes. Exercise is an intervention which helps to maintain glucose homeostasis, and with long‐term adherence, can decrease glucose intolerance and insulin resistance. We have previously demonstrated that a single bout of exhaustive exercise mitigates olanzapine‐induced hyperglycemia. While these findings are encouraging, the clinical relevance of exhaustive exercise in individuals taking olanzapine is limited.Purpose &amp; HypothesesThe purpose of this study was to investigate if increases in short‐term, habitual physical activity in the form of voluntary wheel running (VWR) would have a protective effect against olanzapine‐induced hyperglycemia.Methods10‐week old male C57BL/6J mice remained sedentary or were provided running wheels at the start of the dark cycle (~20:00 h), until the following morning (~8:00 h; start of light cycle). Olanzapine (5 mg/kg body weight (BW)) was administered intraperitoneally (IP) immediately following overnight VWR, or 6 hours and 24 hours post wheel‐lock. Blood glucose was measured at baseline, 30, 60, 90, and 120 mins post‐olanzapine. In parallel experiments following the same overnight VWR protocol, an insulin tolerance test (ITT) (0.5 IU/kg BW; IP) was conducted 60 mins post‐olanzapine treatment to assess olanzapine‐induced insulin resistance among groups.ResultsA single overnight session of VWR protected against acute olanzapine‐induced hyperglycemia immediately post‐wheel lock. This protective effect was still present 6 hours post‐wheel lock, and had reversed by 24 hours after the cessation of exercise. Under insulin‐stimulated conditions, the sedentary olanzapine‐treated mice had significantly higher blood glucose area‐under‐the‐curve compared to the other three groups, providing evidence that a prior bout of VWR protects against olanzapine‐induced insulin resistance. Under insulin‐stimulated conditions, serum free fatty acid concentrations were increased with olanzapine and reduced with VWR.ConclusionsOur findings demonstrate that with a single session of overnight habitual physical activity, olanzapine‐induced hyperglycemia is mitigated for at least 6 hours post‐exercise and insulin‐stimulated glucose disposal is recovered under olanzapine‐treated conditions.Support or Funding InformationThis study was supported by the Canadian Institutes of Health Research.

Study on the relationship between FFA and gout flare.

To detect the serum free fatty acid (FFA) concentration in patients with primary gouty arthritis (GA) and to explore the correlation between FFA and gout flare. Sixty patients with acute GA, 60 patients with GA remission, 60 patients with asymptomatic hyperuricemia (HUA), and 60 normal controls were enrolled in this study. Serum FFA concentration was detected by enzymatic determination in four groups, and the relationship between serum FFA, serum urate (SU), and other clinical and laboratory parameters was analyzed. (1) Serum FFA concentration was significantly higher in the acute GA than in the GA remission, the asymptomatic HUA, and the normal control (H= 72.191, P< 0.001). (2) There were no significant difference in serum triglyceride and low-density lipoprotein cholesterol (LDL-C) concentration between the acute GA, the GA remission, the asymptomatic HUA, and the normal control group. FFA may be involved in the acute attack of gout in conditions of monosodium urate crystal deposition in the joints. Triglyceride and LDL-C may not be involved in the acute attack of gout. FFA may be used as an indicator to monitor the status of GA in clinical.Key Points• Lin Pei and Linfeng Xie designed the randomized controlled trial and were responsible for the development of the protocol.