Lower Free Fatty Acid Levels Research Articles

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.

Effect of Subcritical Carbon Dioxide Extraction and Bran Stabilization Methods on Rice Bran Oil

AbstractThe extraction of rice bran oil using the conventional organic solvent‐based Soxhlet method involves hazardous chemicals, whereas supercritical fluid extraction is a costly high‐temperature operating system. The subcritical carbon dioxide Soxhlet (SCDS) system, which operates at a low temperature, was evaluated for the extraction of rice bran oil in this study. In addition, rice bran that had been subjected to steam or hot‐air stabilization were compared with unstabilized rice bran (control). The yields; contents of tocopherols, tocotrienols and oryzanol; fatty acid profiles; and the oxidative stabilities of the extracted rice bran oils were analyzed. The yields using hexane and SCDS extraction were approximately 22 and 13–14.5 %, respectively. However, oil extracted using the SCDS system contained approximately 10 times more oryzanol and tocol compounds and had lower free fatty acid levels and peroxide values compared with hexane‐extracted oil. Overall, SCDS extraction of steamed rice bran represents a promising method to produce premium‐quality rice bran oil.

Composition and Antiradical Power of Syzygium aromaticum Lipids

2) determine the total phenolic content and in vitro radical scavenging activity of CO. The results from the present study will be used to develop novel edible oil products rich in bioactive molecules with a desirable shelf life. The proportion of lipid classes present in CO as well as the R f values of the subclasses are shown in Table 1. The level of NL was the highest (ca. 94.7%), followed by GL (0.76%) and PL (0.39%). The data are in agreement with Suzuki et al. [13] who analyzed the lipid classes of clove lipidic extract. Subclasses of NL contained triacylglycerol (TG), free fatty acids (FFA), diacylglycerol (DG), esterified sterols (STE), and monoacylglycerol (MG) in decreasing order. A significant amount of TG was found (ca. 96.6% of total NL) followed by a relatively low level of FFA (ca. 1.4% of total NL), while DG and STE were recovered in lower levels. The subclasses of GL found in CO were sulfoquinovosyl diacylglycerol (SQD), digalactosyl diglycerides (DGD), cerebrosides (CER), steryl glycosides (SG), monogalactosyl diglycerides (MGD), and esterified steryl glycosides (ESG) as presented in Table 1. The proportion of each component was estimated by lipid-carbohydrate determination. CER, SG, and ESG were the prevalent components and made up about 92% of the total GL. The PL subclasses in CO were separated into four major fractions via TLC. The TLC fractions of PL revealed that the predominant PL subclasses were PC followed by PE, PI, and PS (Table 1). About half of the total PL was in PC and a quarter was in PE, while PI and PS were isolated in smaller quantities. The fatty acid profiles of CO and lipid classes (NL, GL, and PL) are presented in Table 2. According to the results, nine fatty acids were identified in CO. Linoleic and oleic acids were the main fatty acids in CO. Both fatty acids comprise together about 80% of the total FAME. The cold-pressed oil contained significant levels of monounsaturated fatty acids (MUFA, 39.7 g/100 g total fatty acids), which is comparable to cold pressed hemp, cranberry, blueberry, onion, and milk thistle seed oils but is much lower than the 81 and 82% in carrot and parsley cold pressed seed oils 14, 15.

Mid to Distal Small Bowel Resection with the Preservation of the Terminal Ileum Improves Glucose Homeostasis in Diabetic Rats by Activating the Hindgut-Dependent Mechanism

BackgroundThe aim of this study was to develop a novel surgical model to test the “hindgut hypothesis” and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery. MethodSprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile. ResultThe DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks. ConclusionsThis study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the “hindgut hypothesis” and focused study of biliary enterohepatic recycling in the context of bariatric operations.

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

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

Different postprandial acute response in healthy subjects to three strawberry jams varying in carbohydrate and antioxidant content: a randomized, crossover trial

Dietary food composition influences postprandial glucose homeostasis. Thus, the objective was to investigate the effects of an acute intake of three different types of strawberry jam, differing in carbohydrate and antioxidants content, on postprandial glucose metabolism, lipid profile, antioxidant status, and satiety. Sixteen healthy adults participated in a randomized, crossover, double-blind study with three arms, receiving 60 g of three different strawberry jams. Blood samples were collected at fasting and at 30, 60, 90, and 120 min after its intake. Blood analyses were performed with validated procedures and satiety was estimated with visual analogue scale (VAS). Blood glucose concentrations were maintained at normal values and without peaks within the 2 h after consumption of low-sugar jams. However, blood glucose and insulin were significantly higher at 30 and 60 min after high-sugar (HS) jam intake versus both low-sugar jams. Furthermore, HS jam produced more satisfaction at short time, but decreased as soon as blood glucose concentration began to decrease. Moreover, HS ingestion produced lower free fatty acid levels (p < 0.05) throughout the trial with respect both the low-sugar jams. However, no additional benefits on oxidative status (malondialdehyde, glutathione peroxidase, total antioxidant capacity, and uric acid), glucose, lipid, and satiety variables were observed due to the inclusion of an antioxidant to low-sugar jam. This study reinforces the idea that products without added sugars are appropriate for the management of glycemic alterations and provides further insight into the effect of natural antioxidants as a functional ingredient on oxidative status and related metabolic disturbances. Registered at www.clinicaltrials.gov as NCT01684332.

Effects of PNPLA3 on Liver Fat and Metabolic Profile in Hispanic Children and Adolescents

OBJECTIVEA genome-wide study of adults identified a variant of PNPLA3 (rs738409) associated with ∼twofold higher liver fat. The purpose of this study was to examine the influence of PNPLA3 genotype on liver fat and other related metabolic outcomes in obese Hispanic children and adolescents.RESEARCH DESIGN AND METHODSThree hundred and twenty-seven Hispanics aged 8–18 years were genotyped for rs738409. One hundred and eighty-eight subjects had measures of visceral (VAT) and subcutaneous (SAT) adipose tissue volume and hepatic (HFF) and pancreatic (PFF) fat fraction by magnetic resonance imaging. One hundred and thirty-nine subjects did not have HFF measures but had extensive measures of insulin sensitivity and fasting lipids.RESULTSLiver fat in GG subjects was 1.7 and 2.4 times higher than GC and CC (11.1 ± 0.8% in GG vs. 6.6 ± 0.7% in GC and 4.7 ± 0.9% in CC; P < 0.0001), and this effect was observed even in the youngest children (8–10 years of age). The variant was not associated with VAT, SAT, PFF, or insulin sensitivity or other glucose/insulin indexes. However, Hispanic children carrying the GG genotype had significantly lower HDL cholesterol (40.9 ± 10.9 in CC vs. 37.0 ± 8.3 in CG vs. 35.7 ± 7.4 in GG; P = 0.03) and a tendency toward lower free fatty acid levels (P = 0.06).CONCLUSIONSThese results provide new evidence that the effect of the PNPLA3 variant is apparent in Hispanic children and adolescents, is unique to fat deposition in liver as compared with other ectopic depots examined, and is associated with lower HDL cholesterol.

Genetic variants in adipose triglyceride lipase influence lipid levels in familial combined hyperlipidemia

Objective Familial combined hyperlipidemia (FCHL) has been associated with abnormalities in fatty acid metabolism. The adipose triglyceride lipase (PNPLA2) plays a pivotal role in the turnover of fatty acids in adipose tissue and liver. This study was designed to evaluate whether selected PNPLA2 variants may influence the susceptibility to FCHL or its lipid-related traits. Methods Four SNPs within the PNPLA2 gene (rs7925131, rs7942159, rs66460720 and the nonsynonymous P481L) were selected based on previous association with decreased plasma levels of free fatty acids (FFA) and total triglycerides (TG) and their high frequency (MAF > 0.25). These SNPs were genotyped in 214 FCHL individuals from 83 families and in 103 controls and the corresponding haplotypes were reconstructed. Results No association between individual SNPs and the FCHL trait was observed. However, two PNPLA2 haplotypes were associated with lower risk of FCHL ( P < 0.004 after Bonferroni's correction). Compared to the others, these haplotypes were related to lower TG (118.9 ± 66.8 vs. 197.1 ± 114.7 mg/dl; P = 0.001) and higher HDL-C (62.3 ± 15.8 vs. 51.0 ± 15.0 mg/dl; P < 0.005). In a subgroup of studied subjects ( n = 63) protective haplotypes were also associated with lower FFA levels (0.33 ± 0.11 vs. 0.46 ± 0.18 mEq/L; P < 0.05). These effects were independent from age, BMI and HOMA IR. Conclusion These data demonstrate that variants within PNPLA2 may modulate the TG component of FCHL trait, thus implicating PNPLA2 as modifier gene in this lipid disorder. They also suggest a potential role of PNPLA2 in the metabolism of TG-rich lipoproteins.

Distinct gene expression profiles characterize cellular responses to palmitate and oleate

Obese individuals are both insulin resistant and have high levels of circulating free fatty acids (FFAs). In cell culture, saturated but not unsaturated fatty acids induce endoplasmic reticulum (ER) stress. We hypothesized that chronic exposure to low dose fatty acids would significantly attenuate the acute stress response to a saturated fatty acid challenge and that unsaturated fatty acids (oleate) would be more protective than saturated fatty acids (palmitate). The ER stress response to palmitate was reduced after low dose fatty acid exposure in human hepatoma cells. Palmitate and oleate gave distinctive transcript responses, both acutely and after chronic low dose exposure. Differentially regulated pathways included lipid, cholesterol, fatty acid, and triglyceride metabolism, and IkappaB kinase and nuclear factor kappaB kinase inflammatory cascades. Oleate reduced palmitate-induced changes significantly more than low dose palmitate and completely blocked palmitate-induced phosphoinositide 3 kinase inhibitor (PIK3IP1) as well as induction of GADD45A and B. These changes are predicted to alter the PI3 kinase pathway and the pro-apoptotic p38 MAPK pathway. We recapitulated the oleate response by small interfering RNA-mediated block of PIK3IP1 stimulation with palmitate and significantly protected cells from palmitate-mediated ER stress. We show that transcriptional responses to oleate and palmitate are distinct, broad, and often discordant. We identified several potential candidates that may direct the transcriptional networks and demonstrate that PIK3IP1 partially accounts for the protective effects of oleate.

Circulating Free Fatty Acids do not Contribute to the Acute Systemic Inflammatory Response. An Experimental Study in Porcine Endotoxaemia

Intensive insulin therapy, aiming for strict normoglycaemia, is associated with increased survival in critically ill patients. Insulin therapy concomitantly reduces plasma-free fatty acids. Recent studies indicate that free fatty acids mediate inflammation. In addition to plasma glucose and free fatty acid-lowering effects, insulin also has anti-inflammatory properties. This study was designed to study the pro-inflammatory effects of two free fatty acid concentrations during acute endotoxaemia and controlled comparable levels of plasma glucose and insulin. Twenty pigs were anaesthetized and mechanically ventilated. Pigs were randomized to two different, constant Intralipid infusion rates, throughout observation. All pigs were administered continuous intravenous infusion of endotoxin and subjected to controlled levels of p-glucose (4.5 mmol/l) and insulin by use of a hyperinsulinaemic euglycaemic clamp. Changes in circulating tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, leucocytes, insulin, glucose, free fatty acids, triglycerides, albumin, blood gases, temperature, and, haemodynamic function were monitored. Immediately following killing, biopsies were taken from heart and kidney. Biopsies were analysed for protein content of TNF-alpha, IL-6, IL-8 and IL-10. Sustained elevated and significantly different plasma levels of free fatty acids were demonstrated between groups (mean free fatty acid concentrations, 1.62 mM versus 0.58 mM, p < 0.0002). Endotoxaemia induced a steep increase in plasma TNF-alpha, IL-6 and leucocytes, however, without differences between the low- and high-free fatty acid groups. Cytokine content in heart and kidney tissue was not modified by free fatty acids. Compared with the response obtained at lower free fatty acid levels, high free fatty acid levels did not exacerbate the inflammatory response to acute endotoxaemia. Our results do not support the role of free fatty acids as a significant pro-inflammatory mediator.

Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects.

Normal beta-cells adjust their function to compensate for any decrease in insulin sensitivity. Our aim was to explore whether a prolonged fast would allow a study of the effects of changes in circulating free fatty acid (FFA) levels on insulin secretion and insulin sensitivity and whether any potential effects could be reversed by the antilipolytic agent acipimox. Fourteen (8 female, 6 male) healthy young adults (aged 22.8-26.9 yr) without a family history of diabetes and a body mass index of 22.6 +/- 3.2 kg/m(2) were studied on three occasions in random order. Growth hormone and FFA levels were regularly measured overnight (2200-0759), and subjects underwent an intravenous glucose tolerance test in the morning (0800-1100) on each visit. Treatment A was an overnight fast, treatment B was a 24-h fast with regular administrations of a placebo, and treatment C was a 24-h fast with regular ingestions of 250 mg of acipimox. The 24-h fast increased overnight FFA levels (as measured by the area under the curve) 2.8-fold [51.3 (45.6-56.9) vs. 18.4 (14.4-22.5) *10(4) micromol/l*min, P < 0.0001], and it led to decreases in insulin sensitivity [5.7 (3.6-8.9) vs. 2.6 (1.3-4.7) *10(-4) min(-1) per mU/l, P < 0.0001] and the acute insulin response [16.3 (10.9-21.6) vs. 12.7 (8.7-16.6) *10(2) pmol/l*min, P = 0.02], and therefore a reduction in the disposition index [93.1 (64.8-121.4) vs. 35.5 (21.6-49.4) *10(2) pmol/mU, P < 0.0001]. Administration of acipimox during the 24-h fast lowered FFA levels by an average of 20% (range: -62 to +49%; P = 0.03), resulting in a mean increase in the disposition index of 31% (P = 0.03). In conclusion, the 24-h fast was accompanied by substantial increases in fasting FFA levels and induced reductions in the acute glucose-simulated insulin response and insulin sensitivity. The use of acipimox during the prolonged fast increased the disposition index, suggesting a partial reversal of the effects of fasting on the acute insulin response and insulin sensitivity.

Evaluation of a colorimetric method for measuring the content of FFA in marine and vegetable oils

Free fatty acids (FFA) are produced from triacylglycerides (TAG) through chemical or enzymatic hydrolysis. They are usually associated with undesirable flavour and textural changes when they are present in fats and oils. In the oil processing industry, FFA’s are determined to give an indication of the amount of alkali required to remove them as soaps during the refining stage. This is a titration method requiring considerable time and large amounts of sample for oils containing low levels of FFA. Oils containing low levels of FFA, especially marine oils, showed poor repeatability. When the amount of oil required for the analysis (56 g) was used, an emulsion was formed making difficult to obtain a stable change in colour. FASafe is a rapid colorimetric method requiring less than 1 g of oil. Good agreement between the two methods was obtained at lower levels of FFA (<1.0%). For fish oil samples higher results were obtained by FASafe than the AOCS titration method and results for samples with high levels of FFA tended to be lower by FASafe than by the AOCS method.

Are Patients after Kawasaki Disease at Increased Risk for Accelerated Atherosclerosis?

To assess whether patients after Kawasaki disease (KD) have increased risk factors and abnormalities suggestive of early atherosclerosis in systemic arteries. In a case-control study, we compared 52 patients after typical Kawasaki disease with varying coronary artery involvement (67% males; mean time from illness episode 11.2 +/- 3.7 years) studied between 10 and 20 years of age with 60 healthy control subjects (50% males). Brachial artery reactivity (BAR) was assessed using vascular ultrasonography, and atherosclerosis risk assessment was performed. Differences between cases and controls and factors associated with endothelial function in cases were determined. Case patients had lower resting systolic blood pressure (P < .001), lower apolipoprotein AI levels (P < .05), and higher levels of glycosylated hemoglobin (P = .007). There were no significant differences in BAR between case patients and control subjects in response to increased flow (P = .60) and nitroglycerine (P = .93). For case patients, significant factors in multivariable analysis for lower flow-mediated BAR included higher fasting triglyceride levels (P = .04) and lower free fatty acid levels (P < .001). No significant relationship was noted with past or current coronary artery involvement. Patients with KD have some abnormalities for risk factors for atherosclerosis, but systemic arterial endothelial dysfunction is not present in the long term.

Dose-Response Effects of Free Fatty Acids on Glucose and Lipid Metabolism during Somatostatin Blockade of Growth Hormone and Insulin in Humans

GH and other stress hormones stimulate lipolysis, which may result in free fatty acid (FFA)-mediated insulin resistance. However, there are also indications that FFAs in the very low physiological range have the same effect. The objective of the study was to address systematically the dose-response relations between FFAs and insulin sensitivity. We therefore examined eight healthy men for 8 h (6 h basal and 2 h glucose clamp) on four occasions. Intralipid was infused at varying rates (0, 3, 6, 12 microl.kg(-1).min(-1)); lipolysis was blocked by acipimox; and endogenous GH, insulin, and glucagon secretion was blocked by somatostatin and subsequently replaced at fixed rates. This resulted in four different FFA levels between 50 and 2000 micromol/liter, with comparable levels of insulin and counterregulatory hormones. Both in the basal state and during insulin stimulation, we saw progressively decreased glucose disposal, nonoxidative glucose disposal, and forearm muscle glucose uptake at FFA levels above 500 micromol/liter. Apart from forearm glucose uptake, the very same parameters were decreased at low FFA levels (approximately 50 micromol/liter). FFA rate of disposal was linearly related to the level of FFAs, whereas lipid oxidation reached a maximum at FFA levels approximately 1000 micromol/liter. In the presence of comparable levels of all major metabolic hormones, insulin sensitivity peaks at physiological levels of FFAs with a gradual decrease at elevated as well as suppressed FFA concentrations. These data constitute comprehensive dose-response curves for FFAs in the full physiological range from close to zero to above 2000 micromol/liter.

Pioglitazone Ameliorates Insulin Resistance and Diabetes by Both Adiponectin-dependent and -independent Pathways

Thiazolidinediones have been shown to up-regulate adiponectin expression in white adipose tissue and plasma adiponectin levels, and these up-regulations have been proposed to be a major mechanism of the thiazolidinedione-induced amelioration of insulin resistance linked to obesity. To test this hypothesis, we generated adiponectin knock-out (adipo-/-) ob/ob mice with a C57B/6 background. After 14 days of 10 mg/kg pioglitazone, the insulin resistance and diabetes of ob/ob mice were significantly improved in association with significant up-regulation of serum adiponectin levels. Amelioration of insulin resistance in ob/ob mice was attributed to decreased glucose production and increased AMP-activated protein kinase in the liver but not to increased glucose uptake in skeletal muscle. In contrast, insulin resistance and diabetes were not improved in adipo-/-ob/ob mice. After 14 days of 30 mg/kg pioglitazone, insulin resistance and diabetes of ob/ob mice were again significantly ameliorated, which was attributed not only to decreased glucose production in the liver but also to increased glucose uptake in skeletal muscle. Interestingly, adipo-/-ob/ob mice also displayed significant amelioration of insulin resistance and diabetes, which was attributed to increased glucose uptake in skeletal muscle but not to decreased glucose production in the liver. The serum-free fatty acid and triglyceride levels as well as adipocyte sizes in ob/ob and adipo-/-ob/ob mice were unchanged after 10 mg/kg pioglitazone but were significantly reduced to a similar degree after 30 mg/kg pioglitazone. Moreover, the expressions of TNFalpha and resistin in adipose tissues of ob/ob and adipo-/-ob/ob mice were unchanged after 10 mg/kg pioglitazone but were decreased after 30 mg/kg pioglitazone. Thus, pioglitazone-induced amelioration of insulin resistance and diabetes may occur adiponectin dependently in the liver and adiponectin independently in skeletal muscle.

A New FTIR Method for the Analysis of Low Levels of FFA in Refined Edible Oils

This paper summarizes the application of stoichiometric analytical approaches to quantitative IR analysis and describes the development of a rapid and sensitive Fourier transform infrared (FTIR) method using such an approach for the determination of low levels (<0.005%) of free fatty acids (FFA) in refined edible oils. The method simply involves mixing the sample with methanol containing 2 g /L sodium carbodiimide (NaHNCN) on a vortex mixer for 30 s to convert the FFA to their salts, centrifuging the sample to separate the methanol phase containing the FFA salts from the oil, recording the FTIR spectrum of the upper methanol layer in a 100‐µm CaF2 transmission flow cell, and ratioing this spectrum against that of the NaHNCN/methanol solution. The concentration of FFA salts is determined from the resulting differential spectrum by measurement of the v(COO−) absorbance at 1573 cm−1 relative to a reference wavelength of 1820 cm−1. A calibration spanning the range 0–0.1% FFA (expressed as oleic acid) was devised by gravimetric addition of a defined, pure fatty acid to an acid‐free oil. Validation of the method by standard addition of palmitic acid to a variety of oils yielded an overall standard error of <±0.001% FFA. Comparison of triplicate FTIR and IUPAC titrimetric analyses of oils spiked with palmitic acid demonstrated that this FTIR method was more sensitive, accurate, and reproducible than the titration procedure, the latter having a significant positive bias of ∼0.02%. Solvent/oil consumption in the FTIR method is 2 mL/10 g versus 150 mL/20 g for the titrimetric procedure. The FTIR method developed is particularly well suited for the determination of the low levels of FFA in refined oils but can readily be adapted with a simple adjustment of the oil/methanol ratio to cover FFA levels of up to 4.0%.

Role of premature leptin surge in obesity resulting from intrauterine undernutrition

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."

CONTENT AND STABILITY OF HEXANE EXTRACTABLE LIPID AT VARIOUS STEPS OF PRODUCING MACARONI CONTAINING GROUND FLAXSEED

Research was conducted to determine changes in content and stability of hexane extractable lipid during processing of macaroni containing 15% (w/w) ground whole flaxseed and ground flaxseed hull. Dry mixture, hydrated mixture, extruded macaroni, dried macaroni and cooked macaroni were evaluated. Results were similar for macaroni containing ground whole flaxseed or ground flaxseed hull. Hydration decreased extractable lipid. Hydration decreased the amount of α-linolenic acid (ALA) and free fatty acid (FFA) and increased the amount of conjugated diene in the extracted lipid. Little or no conjugated triene was detected in lipid extracted from samples containing flaxseed, regardless of the processing step. Extruding, drying and cooking had little or no effect on the stability of lipids in macaroni containing flaxseed. The low levels of FFA, conjugated diene and conjugated triene indicate that lipid remained relatively stable during processing and cooking of macaroni containing ground flaxseed.

Impact of different wort boiling temperatures on the beer foam stabilizing properties of lipid transfer protein 1.

Beer consumers demand satisfactory and consistent foam stability; thus, it is a high priority for brewers. Beer foam is stabilized by the interaction between certain beer proteins, including lipid transfer protein 1 (LTP1), and isomerized hop alpha-acids, but destabilized by lipids. In this study it was shown that the wort boiling temperature during the brewing process was critical in determining the final beer LTP1 content and conformation. LTP1 levels during brewing were measured by an LTP1 ELISA, using antinative barley LTP1 polyclonal antibodies. It was observed that the higher wort boiling temperatures ( approximately 102 degrees C), resulting from low altitude at sea level, reduced the final beer LTP1 level to 2-3 microg/mL, whereas the lower wort boiling temperatures ( approximately 96 degrees C), resulting from higher altitudes (1800 m), produced LTP1 levels between 17 and 35 microg/mL. Low levels of LTP1 in combination with elevated levels of free fatty acids (FFA) resulted in poor foam stability, whereas beer produced with low levels of LTP1 and FFA had satisfactory foam stability. Previous studies indicated the need for LTP1 denaturing to improve its foam stabilizing properties. However, the results presented here show that LTP1 denaturation reduces its ability to act as a binding protein for foam-damaging FFA. These investigations suggest that wort boiling temperature is an important factor in determining the level and conformation of LTP1, thereby favoring satisfactory beer foam stability.

Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder

Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. Methods: Patients with a primary DSM-IV diagnosis of ADHD ( N=400; 72 girls, 328 boys, mean age=9.61±1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate ( n=202) (150 mg/day) or placebo ( n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. Results: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. Conclusions: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.