High FFA Levels Research Articles

Fish Liver Discards as a Source of Long-Chain Omega-3 Polyunsaturated Fatty Acids.

The intake of omega-3 polyunsaturated fatty acids (PUFA) of the average consumer is generally low, and products such as fish oils high in omega-3 PUFA have become popular dietary supplements. There is a need for more sources of omega-3 PUFA to cover the increasing demand. This study investigated whether livers from different lean fish species could be a potential new source of oils rich in omega-3 PUFA. The seasonal variation in lipid content, fatty acid composition, peroxide value and free fatty acid content (FFA) of livers from cod, hake, ling, coalfish and monkfish was determined, and the effect of storage conditions on the fishing vessel (ice vs frozen) was studied. Generally, the lipid content and composition of the livers from the five fish species varied similarly during the two years of the sampling period, with significantly lower values in spring (March, April) and higher values in fall (October, November). Storage conditions were found to have no significant effect on the quality and oil composition. Monkfish livers were less suitable for production of omega-3 oil due to their lower lipid and EPA content as well as higher FFA levels. Coalfish had higher fluctuations in oil composition during the sampling period, which potentially makes a standardised quality difficult to obtain. Cod, hake and ling were the most suitable species for fish liver oil production.

TMT-based proteomic and bioinformatic analyses of human granulosa cells from obese and normal-weight female subjects

BackgroundIncreasing evidence supports a relationship between obesity and either infertility or subfertility in women. Most previous omics studies were focused on determining if the serum and follicular fluid expression profiles of subjects afflicted with both obesity-related infertility and polycystic ovary syndrome (PCOS) are different than those in normal healthy controls. As granulosa cells (GCs) are essential for oocyte development and fertility, we determined here if the protein expression profiles in the GCs from obese subjects are different than those in their normal-weight counterpart.MethodsGC samples were collected from obese female subjects (n = 14) and normal-weight female subjects (n = 12) who were infertile and underwent in vitro fertilization (IVF) treatment due to tubal pathology. A quantitative approach including tandem mass tag labeling and liquid chromatography tandem mass spectrometry (TMT) was employed to identify differentially expressed proteins. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then conducted to interrogate the functions and pathways of identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in both groups.ResultsA total of 228 differentially expressed proteins were noted, including 138 that were upregulated whereas 90 others were downregulated. Significant pathways and GO terms associated with protein expression changes were also identified, especially within the mitochondrial electron transport chain. The levels of free fatty acids in both the serum and follicular fluid of obese subjects were significantly higher than those in matched normal-weight subjects.ConclusionsIn GCs obtained from obese subjects, their mitochondria were damaged and the endoplasmic reticulum stress response was accompanied by dysregulated hormonal synthesis whereas none of these changes occurred in normal-weight subjects. These alterations may be related to the high FFA and TG levels detected in human follicular fluid.

Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration

Obesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.

Free Fatty Acids Promote the Development of Prostate Cancer by Upregulating Peroxisome Proliferator-Activated Receptor Gamma.

IntroductionAs one of the most common forms of cancer that threatens men’s health, prostate cancer (PCa) is under a trend of increasing morbidity and mortality in most countries. More and more studies have pointed out that obesity is closely linked to the occurrence and development of PCa, although there are still many undiscovered molecular mechanisms between the two.MethodsIn the present study, we compare serum lipid levels in patients with PCa and normal individuals. PCa cells (PC3 and 22RV1) were cultured in vitro, the TC/TG/HDL/GLU assay kit was used to detect the glucose and lipid metabolism level of PCa cells, the flow cytometry technique was used to detect the proliferation ability of PCa cells, and the Transwell was used to detect the invasion and migration ability of PCa cells. Western blot/quantitative real-time PCR was used to detect peroxisome proliferator-activated receptor γ (PPARγ) and vimentin/vascular endothelial growth factor-A (VEGF-A) expression levels, and immunohistochemistry was used to observe tumor-associated gene expression levels in nude mice. All data were analysed using the Independent samples t-test or rank sum test.ResultsWe found higher levels of FFA in the serum of patients with PCa. In vitro experiments have demonstrated that high levels of FFA can promote the proliferation, migration and invasion of two PCa cells (PC3 and 22RV1) and affect the energy metabolism of PCa cells. The upregulated PPARγ plays a key role in this process, and vimentin may be involved in this signaling pathway.ConclusionWe infer that high levels of FFA may promote PCa development by upregulating PPARγ expression.

A high serum-free fatty acid level is associated with cancer

PurposeThe objectives of this work were to investigate whether the serum-free fatty acid (FFA) level is meaningful in cancer patients and its role in cancer diagnosis.MethodsA total of 2206 patients were divided into a cancer group (n = 1019) and a noncancer group (n = 1187). Age, sex, body mass index (BMI), and serum FFA and serum albumin levels were collected. Cancer patients were divided into subgroups according to the location of the cancer. We then compared serum FFA levels among the tumor subgroups. A receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of the FFA level. SPSS 22.0 software was used to analyze the results.ResultsThe FFA level was higher in the cancer group than in the noncancer group. According to the multivariate analysis, there was also an increased risk of cancer associated with a high FFA level after adjusting for old age, female sex, and a low BMI. In the subgroup analysis, the FFA level in patients with lung cancer, gastric cancer, thyroid cancer, rectal cancer, colon cancer, and ovarian cancer was significantly higher than that in noncancer patients. The area under the effect–time curve (AUC) of FFAs in the whole cancer group was 0.58, while the thyroid cancer, rectal cancer, and ovarian cancer subgroups had AUCs > 0.6.ConclusionOur study provides clinical evidence to support that fatty acid metabolism is associated with cancers and demonstrates that a high FFA level in the serum may be an indicator of cancer.

2147-P: Pancreatic Specific Deletion of NOS1AP Lowered Islet Mass

Objective: Nitric oxide synthase associated protein (NOS1AP) is an adaptor protein regulating neuronal functions through NMDAR/nNOS-dependent pathway. We previously reported that NOS1AP SNP rs12742393 was associated with type 2 diabetes. In the present study we aimed to investigate the effect of NOS1AP on beta-cell function. Methods: Pancreatic specific deletion (CKO) of NOS1AP mice were generated from floxed nos1ap (exon 3-5) mice and pdx1-cre mice. These mice were fed with either chow or high fat diet (HFD,60% kcal fat). Results: NOS1AP was highly expression in mouse islets. Deletion of NOS1AP in pancreas had no effect on food intake and body weight in mice either fed with chow and high fat diet. However, deletion of NOS1AP impaired glucose tolerance in HFD fed mice. The blood glucose levels at 15min and 30min were higher in CKO than in its littermate control mice. The AUC of IPGTT in CKO was 20% higher than that in control mice. Insulin levels in CKO mice were lower than that in control mice after glucose load (P<0.05). Similarly, glucose stimulated insulin secretion from islets isolated from CKO was decreased compared with that from control mice. Moreover, islet mass in mice with pancreatic NOS1AP deletion decreased significantly (P<0.05). BrdU staining showed that the BrdU positive cells in islets were lower in NOS1AP CKO mice than in control mice. Overexpression of NOS1AP protected beta-cells from high levels of glucose and FFA (palmitate)-induced cell death. Conclusion: Our data demonstrate that NOS1AP plays a role in regulating beta-cell function and mass through regulation of cell proliferation and cytoprotection. Disclosure C. Wang: None. Q. Mao: None. Q. Li: None. W. Jia: None. Funding National Natural Science Foundation of China (81670707)

HORMONAL REGULATION OF CARBOHYDRATE AND FAT METABOLISM IN WOMEN WITH DIFFERENT OBESITY TYPES IN THE FOOD DEPRIVATION TEST.

The dominant type of adipose tissue accumulation in the body is associated with the peculiarities of using key substrates in energy metabolism and their hormonal regulation. Hormonal and metabolic parameters were investigated in women with android and gynoid obesity before and after the short-term food deprivation test. At baseline, at gynoid obesity as compared to android obesity, the women's blood contained lower glucose and insulin levels and higher FFA levels. The reaction to food deprivation manifested by a decrease in glucose level and an increase in FFA level in the blood is less pronounced in women with gynoid obesity than in those with android obesity. At the same time, a similar (though varying in expression) decrease in insulin level and elevated levels of glucagon, growth hormone and thyroxine were revealed in women's blood in both groups. Blood cortisol level increased in women with gynoid obesity and remained unchanged in those with android obesity. More pronounced activation of hormonal mechanisms for maintaining blood glucose levels at gynoid obesity as compared to android one suggests that glucose is the preferable substrate for energy metabolism at gynoid obesity in women.

Liraglutide protects against glucolipotoxicity-induced RIN-m5F β-cell apoptosis through restoration of PDX1 expression.

Prolonged exposure to high levels of glucose and fatty acid (FFA) can induce tissue damage commonly referred to as glucolipotoxicity and is particularly harmful to pancreatic β‐cells. Glucolipotoxicity‐mediated β‐cell failure is a critical causal factor in the late stages of diabetes, which suggests that mechanisms that prevent or reverse β‐cell death may play a critical role in the treatment of the disease. Transcription factor PDX1 was recently reported to play a key role in maintaining β‐cell function and survival, and glucolipotoxicity can activate mammalian sterile 20‐like kinase 1 (Mst1), which, in turn, stimulates PDX1 degradation and causes dysfunction and apoptosis of β‐cells. Interestingly, previous research has demonstrated that increased glucagon‐like peptide‐1 (GLP‐1) signalling effectively protects β cells from glucolipotoxicity‐induced apoptosis. Unfortunately, few studies have examined the related mechanism in detail, especially the role in Mst1 and PDX1 regulation. In the present study, we investigate the toxic effect of high glucose and FFA levels on rat pancreatic RINm5F β‐cells and demonstrate that the GLP‐1 analogue liraglutide restores the expression of PDX1 by inactivating Mst1, thus ameliorating β‐cell impairments. In addition, liraglutide also upregulates mitophagy, which may help restore mitochondrial function and protect β‐cells from oxidative stress damage. Our study suggests that liraglutide may serve as a potential agent for developing new therapies to reduce glucolipotoxicity.

Dapagliflozin Improves Insulin Sensitivity in the Obese Prediabetic Canine

SGLT2 inhibition has positive effects on glucose balance, reducing fasting and postprandial glucose levels, however little is known about the effects of SGLT2 inhibitors on lipid levels. PKPD simulation for this canine model was applied for dose selection of dapagliflozin (dapa). Seven dogs were fed a high fat diet for 6 weeks, then received a single low dose of streptozotocin (18.5mg/kg) to induce mild type 2 diabetes. Animals were exposed to dapa (n=4, 1.25mg/kg) or placebo (n=3) once per day for 6 weeks, while remaining on the high fat diet. Animals were then subjected to the intravenous glucose tolerance test (IVGTT) to assess glucose tolerance and insulin response to glucose, and the euglycemic hyperinsulinemic clamp protocol in conjunction with tracer infusions to evaluate adipose tissue, skeletal muscle and hepatic insulin sensitivity. In the IVGTT, modeling techniques are used to estimate the acute insulin response to a glucose bolus, which was not altered with dapa treatment, but insulin sensitivity was significantly improved compared to placebo-treated animals (dapa 0.54±0.22, control -0.95±0.51mU/l-1.minute-1, p=0.05). The glucose infusion required for euglycemia during steady state in the clamp was decreased with dapa (dapa -3.0±1.05, control 1.53±1.28 mg/minute/kg, change from pre-drug timepoint, P=0.038), supporting the IVGTT results. Urinary glucose disposal rate during the clamp was inconsistent. There is a trend towards higher FFA levels in dapa-treated animals under noninsulin stimulated conditions (P=0.054). These may be a regulator of hepatic glucose production, or reflect a switch towards lipid utilization. We conclude that 6 weeks of dapa treatment improves insulin sensitivity in a canine model of mild type 2 diabetes. Further studies on lipid metabolism, body fat deposition and insulin clearance are on-going. Disclosure R.L. Paszkiewicz: None. R.N. Bergman: Advisory Panel; Self; Ingredion, Inc.. Research Support; Self; AstraZeneca. Consultant; Self; GI Dynamics Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Self; Novo Nordisk A/S. I. Asare Bediako: None. H.J. Mkrtchyan: None. V. Gopaul: Employee; Self; AstraZeneca. H. Yang: Employee; Self; AstraZeneca. E. Lundborg: Employee; Self; AstraZeneca. S. Kim: None. I. Formentini: Employee; Self; AstraZeneca. C.M. Kolka: Research Support; Self; AstraZeneca.

Effective synthesis of biodiesel from Jatropha curcas oil using betaine assisted nanoparticle heterogeneous catalyst from eggshell of Gallus domesticus

The recovery of waste as feedstock away from organizational limitations corresponds to a prospective supplementary revenue stream for the organization. A novel waste eggshell of Gallus domesticus derived superbasic nanocatalyst was synthesized through betaine amphoteric surfactant-assisted decomposition, adsorption and precipitation processes. By varied the duration synthesis of gel mixture, the morphology transformation from liquid-solid interconnected macro-size particles to regular spheroidal nanoassemblies particles is detected. The surfactant at the liquid-solid interface facilitates the mono dispersion of nanoparticles by hindering growth of crystals. The average particle diameter of the produced superbasic nanocatalyst was in the range of 27–16 nm. The synthesized nanoparticle formation mechanism in the presence surfactant has also been addressed in this study. The catalytic activity of superbasic nanocatalyst was investigated for biodiesel production from crude Jatropha curcas oil (JCO) via glycerolysis and transesterification with methanol at atmospheric pressure. Artificial neural network (ANN) based on the genetic algorithm (GA) was applied for optimization of varied reaction parameters. It was observed that the reduction of acidity varied with varying reaction conditions. The highest fatty acid methyl ester (FAME) yield (97%) was obtained when the reaction was allowed to run at 60 °C for 300 min, while at 90 °C the maximal FAME yield of 98% was achieved after 120 min. The kinetic parameters of nanocatalyst were determined, and the reaction system followed pseudo first order kinetics. The results suggest that this two steps process using superbasic nanocatalyst affords a promising method to convert oils with high FFA level to biodiesel.

Leptin signal transduction underlies the differential metabolic response of LEW and WKY rats to cafeteria diet.

Although the effect of genetic background on obesity-related phenotypes is well established, the main objective of this study is to determine the phenotypic responses to cafeteria diet (CAF) of two genetically distinct inbred rat strains and give insight into the molecular mechanisms that might be underlying. Lewis (LEW) and Wistar-Kyoto (WKY) rats were fed with either a standard or a CAF diet. The effects of the diet and the strain in the body weight gain, food intake, respiratory quotient, biochemical parameters in plasma as well as in the expression of genes that regulate leptin signalling were determined. Whereas CAF diet promoted weight gain in LEW and WKY rats, as consequence of increased energy intake, metabolic management of this energy surplus was significantly affected by genetic background. LEW and WKY showed a different metabolic profile, LEW rats showed hyperglycaemia, hypertriglyceridemia and high FFA levels, ketogenesis, high adiposity index and inflammation, but WKY did not. Leptin signalling, and specifically the LepRb-mediated regulation of STAT3 activation and Socs3 gene expression in the hypothalamus were inversely modulated by the CAF diet in LEW (upregulated) and WKY rats (downregulated). In the present study, we show evidence of gene-environment interactions in obesity exerted by differential phenotypic responses to CAF diet between LEW and WKY rats. Specifically, we found the leptin-signalling pathway as a divergent point between the strain-specific adaptations to diet.

Chemical and microbiological characteristics of traditional homemade fresh goat cheeses from Northern Morocco

A chemical and microbiological survey was performed on 28 fresh raw goat's milk cheeses from Northern Morocco. Cheeses were characterized by their low pH values (3.81–4) and low dry matter contents (24.9–31.2g/100g). Fat, protein and ash contents were 14. 4–17.1, 8.3–10.3, and 1.12–1.75g/100g, respectively. High levels of FFA were determined (3260–3507mg/kg), the most abundant being oleic, stearic, palmitic, myristic and capric acid. Lactic acid bacteria (LAB) were the dominant microbiota (7.9–9.7logcfu/g), and yeasts and total coliforms were also present in high numbers (5–7logcfu/g). Salmonella spp. was not detected in any of the cheese samples. Listeria monocytogenes was detected in four cheeses. A total of 294 LAB isolates were identified by PCR as Enterococcus spp. (249 isolates), Lactococcus lactis (36), Lactobacillus plantarum (7) and L. paracasei (2).

Lipid, adipokine and ghrelin levels in myocardial infarction patients with insulin resistance

BackgroundInsulin resistance (IR) is a risk factor for ischaemic heart disease and myocardial infarction (MI). IR often manifests in MI and is regarded as an independent predictor of in-hospital mortality, which can provide early risk stratification for recurrent acute coronary events.MethodsThe study enrolled 200 patients (130 males and 70 females aged 61.4 ± 1.12 years) diagnosed with ST elevation MI. At days 1 and 12 from the MI onset, IR levels and lipid profiles, as well as serum glucose, insulin, adipokine and ghrelin levels, were measured.ResultsFree fatty acid (FFA) levels had the most pronounced changes: IR patients had a 9-fold increase in FFA levels at day 1, and patients without IR had a 6-fold increase. Leptin levels at days 1 and 12, in IR patients were, on average, 1.5- and 2-fold higher compared to the controls and patients with no IR (р < 0.05). Leptin levels in IR patients were increased throughout the entire hospital stay. Resistin levels in IR patients were, on average, 1.4-fold higher throughout the entire hospital stay, while in non-IR patients, resistin levels were similar to the controls. Adiponectin levels in IR patients were decreased compared to the controls, while in patients with IR, they were similar to the controls. Both IR and non-IR MI patients had 3-fold and 3.7-fold lower ghrelin levels at day 1, respectively, compared to the controls. The correlation analysis showed a negative correlation between ghrelin and FFA (r = −0.48 р = 0.007), ghrelin and leptin (r = −0.4 р = 0.003), ghrelin and insulin (r = −0.54 р = 0.002), and ghrelin and glucose (r = −0.31 р = 0.002) in MI patients.ConclusionDyslipidaemia, along with insulinaemia and glycaemia, is one of the most significant IR risk factors in the acute and early recovery phases of MI. Dyslipidaemia is characterised by a high FFA level; an imbalance of leptin, resistin, and adiponectin; and a deficiency of ghrelin in the acute and early recovery periods of MI. FFA and ghrelin can be used as promising molecular markers to stratify the risk of recurrent acute coronary events and diabetes mellitus in MI patients.

Effects of dietary lipid sources on performance and apparent total tract digestibility of lipids and energy when fed to nursery pigs1

Acidulated fats and oils are by-products of the fat-refining industry. They contain high levels of FFA and are 10% to 20% less expensive than refined fats and oils. Two studies were designed to measure the effects of dietary lipid sources low or high in FFA on growth performance and apparent total tract digestibility (ATTD) of lipids and GE in nursery pigs. In Exp. 1, 189 pigs at 14 d postweaning (BW of 9.32 ± 0.11 kg) were used for 21 d with 9 replicate pens per treatment and 3 pigs per pen. Dietary treatments consisted of a control diet without added lipids and 6 diets with 6% inclusion of lipids. Four lipid sources were combined to create the dietary treatments with 2 levels of FFA (0.40% or 54.0%) and 3 degrees of fat saturation (iodine value [IV] = 77, 100, or 123) in a 2 × 3 factorial arrangement. Lipid sources were soybean oil (0.3% FFA and IV = 129.4), soybean-cottonseed acid oil blend (70.5% FFA and IV = 112.9), choice white grease (0.6% FFA and IV = 74.8), and choice white acid grease (56.0% FFA and IV = 79.0). Addition of lipid sources decreased ADFI (810 vs. 872 g/d; P = 0.018) and improved G:F (716 vs. 646 g/kg; P < 0.001). Diets high in FFA tended (P = 0.08) to improve final BW (21.35 vs. 21.01 kg) and ADG (576 vs. 560 g/d). Lipid-supplemented diets had greater ATTD of lipids than control diets (67.4% vs. 29.7%; P < 0.001). Apparent total tract digestibility of lipids was greater in diets with low FFA (69.9% vs. 64.9%; P < 0.001) and decreased linearly with increasing IV (73.2%, 69.1%, and 67.2%). For GE, ATTD was greater in diets with low FFA (83.1% vs. 80.9%; P = 0.001). In Exp. 2, 252 pigs at 7 d postweaning (BW of 7.0 ± 0.2 kg) were used for 28 d with 9 replicate pens per treatment and 4 pigs per pen. Diets included a control diet without added lipids and 6 treatments with 2.5%, 5.0%, or 7.5% of lipids from either poultry fat (1.9% FFA) or acidulated poultry fat (37.8% FFA) in a 2 × 3 factorial arrangement. Addition of lipids increased (P < 0.001) final BW (19.9 vs. 18.4 kg) and ADG (460 vs. 405 g/d) regardless of source. Fat increased (P < 0.001) ADFI when added at 2.5% and then decreased ADFI with each further increment (663, 740, 681, and 653 g for 0%, 2.5%, 5.0%, and 7.5% fat, respectively). Inclusion of lipids linearly (P < 0.001) improved G:F (615, 615, 688, and 692 g/kg for 0%, 2.5%, 5.0%, and 7.5% fat, respectively) and ATTD of lipids (17.8%, 50.2%, 71.0%, and 77.3% for 0, 2.5, 5.0, and 7.5% fat, respectively) and GE (76.1%, 76.4%, 83.3%, and 84.4% for 0%, 2.5%, 5.0%, and 7.5% fat, respectively). Acidulated lipids resulted in similar performance compared with refined lipids and could be economical alternatives to more expensive lipid sources.

Clinical characteristics and heterogeneity in patients with ketosis-prone diabetes

Objective To investigate the clinical characteristics,peripheral insulin sensitivity,and β-cell function in patients with ketosis-prone diabetes(KPD).Methods Thirty-one patients with newly diagnosed ketosisprone diabetes were admitted to West China Hospital from January 2004 to December 2009.They were divided into 2 groups according to their body mass index (BMI):OB-KPD (BMI ≥ 25 kg/m2,n =22) and Lean-KPD (BMI ＜ 23 kg/m2,n =9).10 patients with newly-onset type 2 diabetes free from ketosis (OB-DM:BMI ≥ 25 kg/m2,n =10) were enlisted as control.Detailed assessments of medical history and symptoms of hyperglycemia were performed.The islet cell antibody (ICA),insulin autoantibody (IAA),anti-glutamic acid decarboxylase antibody (GAD-Ab),fasting plasma glucose,serum insulin,C-peptide and free fat acids concentrations were measured.All of the subjects underwent oral and intravenous glucose tolerance tests,euglycemic-hyperinsulinemia and hyperglycemia clamp test,to evaluate the insulin secretion and insulin sensitivity respectively.Insulin sensitivity was determined by glucose disposal rate (GDR) of steady state during euglycemic clamp and acute insulin secretion was calculated by insulin area under curve(AUCins 0-10 min) during IVGTT.Maximal insulin secretion was determined by glucose infusion rate (GIR) and serum insulin concentration of steady state during hyperglycemic clamp test.Results Age,sex,duration of diabetes were matched among groups.A family history of diabetes was strongly associated with those patients with obesity,compared with lean ketosis prone diabetes(16/22 vs 1/9).GDR was (4.91 ± 1.82) mg · kg 1 · min-1 in subjects with OB-KPD,being lower than that in Lean-KPD patients[(6.26 ± 1.89) mg · kg 1 · min-1] and OB-DM group[(6.78-± 1.69) mg · kg 1 · min-1,P＜0.01].Serum insulin and C-peptide in OB-KPD patients were higher than Lean-KPD patients.Area under the insulin curve [AUCins0-10min (183.86 ± 31.1) mIU/L] and GIR[(2.65 ±1.53) mg · kg-1 · min-1] in OB-KPD patients were lower than those in OB-DM group[(697.06-± 231.9) mIU/L,(6.53 ± 2.21)mg · kg 1 · min-1,P＜0.0 1],but slightly higher than the Lean-KPD group [AUCins0 10min (92.1 ±29.8) mUU/L,GIR (2.55 ± 1.49) mg · kg 1 · min-1,P＜0.05].Glucose disposal rate (GDR) was strongly associated with casual plasma glucose (r =-0.502,P＜0.01),HbA1C(r =-0.553,P＜0.0 1) and FFA eoneentrations (r=-0.504,P＜0.01) on admission.Conclusions Insulin resistance and β-cell dysfunction coexist in all KPD patients.OB-KPD patients exhibit more severe insulin resistance,while Lean-KPD patients have lower insulin secretion.KPD patients had severe hyperglycemia,hypertriglyceridemia,and high plasma FFA levels on admission,suggesting that hyperglycemia and elevated FFA levels could result in serious insulin resistance,β-cell dysfunction,and diabetic ketosis in patients with KPD. Key words: Diabetes mellitus ; Ketosis ; β-cell function

Effect of Paraxanthine on Body Fat Reduction and Insulin Sensitivity in Monosodiun Glutamate-Obese Rats

Purpose：To evaluate the effects of body fat reduction on insulin sensitivity, it was measured the glucose disappearance rate, glucose infusion rate, and hepatic glucose production rate after paraxanthine (1,7-dimethylxanthine, metabolite of caffeine) treatment in monosodium -L-glutamate (MSG)-obese rats. Materials and Methods：Obesity was induced by neonatal (2, 4, 6, 8, 10 days) injection of MSG(4 g/kg, subcutaneously) for 15 weeks. MSG-obese rats showed severe fat deposition in subcutaneous and intraabdominal cavity, shortened body length, normoglycemia, hyperinsulinemia, and high FFA level. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique under anesthesia with pentothal sodium. Plasma insulin concentration was clamped at 100　μU/ml by continuous insulin infusion (1.5 mU/kg/min). At steady state, the glucose disappearance rate and glucose infusion rate were decreased and the hepatic glucose production rate was increased in the MSG-obese rats compared to the normal rats. Results：At 15 weeks of age, paraxanthine (15 mg/kg) was administered with ephedrine (60 mg/kg) via per oral for 15 consecutive days. Body fat mass of the paraxanthine treated rats was decreased about 29.6% in the MSG-obese and 6.3% in the normal rats compared with the control rats during 15 days. In the paraxanthine treated MSG-obese rats, the fasting insulin level was significantly (p<0.05) decreased and the glucose infusion rate was significantly (p<0.05) increased compared to that of the MSG-control rats, however the glucose disappearance rate showed increasing tendency and the hepatic glucose production rate showed decreasing tendency compared to that of the MSG-control rats. Conclusion：These results suggest that paraxanthine exerts an anti-obesity effect and improve insulin sensitivity in rats with MSG-induced obesity.

Biodiesel production from crude Jatropha curcas L. seed oil with a high content of free fatty acids

A technique to produce biodiesel from crude Jatropha curcas seed oil (CJCO) having high free fatty acids (15%FFA) has been developed. The high FFA level of JCJO was reduced to less than 1% by a two-step pretreatment process. The first step was carried out with 0.60 w/w methanol-to-oil ratio in the presence of 1% w/w H 2SO 4 as an acid catalyst in 1-h reaction at 50 °C. After the reaction, the mixture was allowed to settle for 2 h and the methanol–water mixture separated at the top layer was removed. The second step was transesterified using 0.24 w/w methanol to oil and 1.4% w/w NaOH to oil as alkaline catalyst to produce biodiesel at 65 °C. The final yield for methyl esters of fatty acids was achieved ca. 90% in 2 h.

Relationship between lipoprotein lipase and peroxisome proliferator-activated receptor-α expression in rat liver during development

The present study was addressed to determine whether the high expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in rat liver during the perinatal stage plays a role in the induction of liver lipoprotein lipase (LPL) expression and activity. Parallel increases in liver mRNA PPAR-alpha and LPL activity were found in newborn rats, and after a slight decline, values remained elevated until weaning. Anticipated weaning for 3 days caused a decline in those two variables as well as in the mRNA LPL level, and a similar change was also found in liver triacylglycerol concentration. Force-feeding with Intralipid in 10-day-old rats or animals kept fasted for 5 h showed high mRNA-PPARalpha and -LPL levels as well as LPL activity with low plasma insulin and high FFA levels, whereas glucose and a combination of glucose and Intralipid produced low mRNA-PPARalpha and -LPL levels as well as LPL activity. Under these latter conditions, plasma insulin and FFA levels were high in those rats receiving the combination of glucose and Intralipid, whereas plasma FFA levels were low in those force-fed with glucose. It is proposed that the hormonal and nutritional induction of liver PPAR-alpha expression around birth and its maintained elevated level throughout suckling is responsible for the induction of liver LPL-expression and activity during suckling.

Biodiesel production from mahua (Madhuca indica) oil having high free fatty acids

Abstract A technique to produce biodiesel from mahua oil ( Madhuca indica ) having high free fatty acids (19% FFA) has been developed. The high FFA level of mahua oil was reduced to less than 1% by a two-step pretreatment process. Each step was carried out with 0.30–0.35 v/v methanol-to-oil ratio in the presence of 1% v/v H 2 SO 4 as an acid catalyst in 1-hour reaction at 60°C. After the reaction, the mixture was allowed to settle for an hour and methanol–water mixture that separated at the top was removed. The second step product at the bottom was transesterified using 0.25 v/v methanol and 0.7% w/v KOH as alkaline catalyst to produce biodiesel. The fuel properties of mahua biodiesel were found to be comparable to those of diesel and conforming to both the American and European standards.

Gestational diabetes exhibits lack of carnitine deficiency despite relatively low carnitine levels and alterations in ketogenesis

Objective: Previous studies have underlined the importance of the carnitine shuttle system and its dysfunction both in normal pregnancy and in type 1 and 2 diabetes. The objective of this paper was to delineate more systematically the role of the carnitine shuttle system in normal pregnancy and in gestational diabetes.Methods: A total of 119 women matched for age comprised three groups: 40 normal adult non-pregnant women (NNP), 46 normal pregnant women with uncomplicated pregnancy (NP) and 33 women with gestational diabetes (GDM). The latter group was further subdivided into those being managed either by diet alone (25 women, GDM-D) or by insulin (8 women, GDM-I). The following biochemical parameters were assayed: fasting plasma total, free and acyl-carnitine, FFA and β-OH-butyrate, together with several essential anthropometric parameters.Results: Women with GDM, in contrast to the control groups, displayed the biochemical features characteristic of insulin resistance: higher body weight, higher BMI, higher skinfold and higher HbA1c levels. No differences on any parameters were found between the two GDM subgroups. Both NP and GDM groups had low levels of total carnitine compared to NNP control group, but surprisingly, the GDM group did not exhibit any further decrease of carnitine levels, as would have been expected by the combination of pregnancy and diabetes. Both groups, despite these low carnitine levels, had no clinical symptoms of carnitine deficiency. Furthermore, the GDM group displayed higher levels of FFA and β-hydroxybutyrate, which were statistically significant compared to the other two control groups.Conclusions: The data corroborate the negative effect of normal gestation on the carnitine shuttle system, while they document for the first time that GDM does not further affect the efficiency of the carnitine system. The mild effect of GDM on carnitine status could be explained by the concurrent increased gluconeogenesis, a process which does not affect directly carnitine metabolism.