Lipid Oxidation Capacity Research Articles

Fibre type-dependent response of broiler muscles to dietary antioxidant supplementation for oxidative stability enhancement

ABSTRACTThe influence of dietary antioxidants and quality of oil on the oxidative and physico-chemical properties of chicken broiler breast and thigh meat stored was studied in either an oxygen-enriched (HiOx: 80% O2/20% CO2) or an air-permeable polyvinylchloride (PVC) packaging system during retail display at 2–4°C for up to 14 and 7 d, respectively.Broilers were fed on a diet with either a low-oxidised (peroxide value (POV) 23 meq O2/kg) or a high-oxidised (POV 121 meq O2/kg) oil, supplemented with or without an algae/selenium-based antioxidant with organic minerals, for 42 d.Lipid and protein oxidation, myofibrillar protein profile and purge loss were analysed. In both packaging systems, lipid oxidation (thiobarbituric acid-reactive substances [TBARS]) was inhibited by up to 65% and 57% in chicken breast and thigh, respectively, with an antioxidant-supplemented diet compared to those without. In both breast and thigh samples, protein sulfhydryls and water-holding capacity (purge loss) were better protected by the antioxidant dietary treatment, regardless of oil quality.Thigh muscles had up to sevenfold greater TBARS formation and more myosin heavy chain losses compared to breast samples. Antioxidant supplementation was more protective against lipid oxidation and water-holding capacity in the group fed on high-oxidised oil compared to those fed on low-oxidised oil.The results suggest that dietary antioxidants can minimise the negative impact of oxidised oil on broiler meat quality, and this protection was more pronounced for thigh than breast muscle, indicating inherent variations between muscle fibre types.

EndoG Knockout Mice Show Increased Brown Adipocyte Recruitment in White Adipose Tissue and Improved Glucose Homeostasis

Brown adipose tissue (BAT) plays a central role in the regulation of whole-body energy and glucose homeostasis owing to its elevated capacity for lipid and glucose oxidation. The BAT thermogenic function, which is essential for the defense of body temperature against exposure to low environmental temperatures, relies on the expression in the inner membrane of brown adipocyte's mitochondria of uncoupling protein-1, a protein that uncouples substrate oxidation from oxidative phosphorylation and leads to the production of heat instead of ATP. BAT thermogenesis depends on proper mitochondrial biogenesis during the differentiation of brown adipocytes. Despite the data that support a role for Endonuclease G (EndoG) in the process of mitochondrial biogenesis, its function in BAT has not been explored. Here, using an EndoG knockout mouse model, we demonstrate that EndoG is not essential for the expression of mitochondrial genes involved in substrate oxidation or for the induction of thermogenic genes in BAT in response to cold exposure. We also show that a lack of EndoG is associated with an increased expression of thermogenic genes (ie, uncoupling protein-1, peroxisome proliferator-activated receptor-γ coactivator-1α) in white adipose tissue (WAT) that correlates with the appearance of brown adipocyte-like cells interspersed among white adipocytes. Interestingly, the increased browning of WAT elicited by the lack of EndoG was associated with a better glucose tolerance and reduced fat mass. Our results suggest that the induction of browning in WAT by means of inhibiting EndoG activity appears as a potential therapeutic strategy to prevent obesity and ameliorate glucose intolerance.

Quality of deli-style turkey enriched with plant sterols.

Low-fat meat products could be excellent carriers for plant sterols, known for their cholesterol-lowering properties. In this study, we developed a protocol for the manufacture of a deli-style turkey enriched with plant sterols (S) at a level sufficient to deliver the maximum plant sterols amount recommended for cholesterol reduction by the European Food Safety Authority (3 g of plant sterols per day) in a 70 g portion. We investigated the stability of the plant sterols and the effects of their addition on the product quality. Plant sterols remained stable during the seven-day storage period. The addition of plant sterols significantly affected some texture parameters, shear force, lipid oxidation, L values and water-holding capacity compared with control (C). Sensory analysis was carried out by an untrained panel (32) using the difference-from-control test between C and S samples to evaluate first the extent of the overall sensory difference and then the extent of sensory difference on colour, texture and flavour. Results indicated that panellists considered the intensity of the difference between C and S samples to be 'small'. Plant sterols could be used as a potential health-promoting meat ingredient with no effect on plant sterol stability but with some effects on texture and sensory characteristics.

Effect of turmeric powder (Curcuma longa L.) and ascorbic acid on antioxidant capacity and oxidative status in rabbit burgers after cooking

<p>The aim of this study was to evaluate the effects of turmeric powder and ascorbic acid on lipid oxidation and antioxidant capacity in cooked rabbit burgers. The burgers were derived from 3 different formulations (C, control, with no additives; Tu with 3.5% of turmeric powder and AA with 0.1% of ascorbic acid) and were stored at 4°C for 0 and 7 d and cooked. The lipid oxidation (thiobarbituric acid reactive substances [TBARS]) and antioxidant capacity (2,2-azinobis-[3 ethylbenzothiazoline-6-sulfonic acid] {ABTS}, 1,1-diphenyl-2-pircydrazyl [DPPH] and ferric reducing ability [FRAP]) were evaluated. A significant interaction between storage time and formulation (P<0.001) was observed for DPPH, FRAP and TBARS in cooked burgers. At day 0 and day 7, the DPPH value was higher in Tu and AA compared to C burgers. At day 0, C showed a lower level of FRAP than the Tu and AA burgers. At day 7, the FRAP values tended to decrease but remained significantly higher in Tu and AA compared to C burgers. Lipid oxidation at day 0 in Tu and AA showed lower TBARS values compared to C burgers. The addition of 3.5% turmeric powder in rabbit burgers exerts an antioxidant effect during storage and it seems more effective in controlling lipid oxidation than ascorbic acid after cooking.</p>

Effect of Turmeric (Curcuma longaL.) Powder as Dietary Antioxidant Supplementation on Pig Meat Quality

The aim of this study was to evaluate the effect of dietary Curcuma longa powder on pig meat quality and shelf-life. Eighteen pigs (Cinta Senese breed) were fed with two different diets: basal diet (control, C) and basal diet supplemented with 4.5 g/pig/day of turmeric powder (Tu). After slaughter meat quality was assessed during 7 days of storage at 4C. pH, color, drip loss, cooking loss, tenderness, lipid oxidation and antioxidant capacity were determined at day 0 and 7 on raw samples. Dietary turmeric powder induced reductions in a* and b* indexes and in Chroma. Lipid oxidation was lower in meat from Tu diet than C diet (P < 0.05). The C. longa powder supplementation did not affect pH, drip loss, cook loss, tenderness, L* and antioxidant capacity (P > 0.05). Turmeric powder could thus be a potential supplementation in diet of pigs for increasing meat quality. Practical Applications Recently, purchasers and producers pay much attention on meat quality. Autochthonous pig breeds, like Cinta Senese, are known for their high meat quality and are sought after by consumers. Natural feed supplementation appears to be a viable management operation to improve the quality and stability of the meat. Turmeric is one of the most popular spice used around the world and it is studied for its antioxidant power. The dietary supplementation of turmeric in pigs can increase meat quality and extend shelf-life.

P46Shc Inhibits Thiolase and Lipid Oxidation in Mitochondria

Although the p46Shc isoform has been known to be mitochondrially localized for 11 years, its function in mitochondria has been a mystery. We confirmed p46Shc to be mitochondrially localized and showed that the major mitochondrial partner of p46Shc is the lipid oxidation enzyme 3-ketoacylCoA thiolase ACAA2, to which p46Shc binds directly and with a strong affinity. Increasing p46Shc expression inhibits, and decreasing p46Shc stimulates enzymatic activity of thiolase in vitro Thus, we suggest p46Shc to be a negative mitochondrial thiolase activity regulator, and reduction of p46Shc expression activates thiolase. This is the first demonstration of a protein that directly binds and controls thiolase activity. Thiolase was thought previously only to be regulated by metabolite balance and steady-state flux control. Thiolase is the last enzyme of the mitochondrial fatty acid beta-oxidation spiral, and thus is important for energy metabolism. Mice with reduction of p46Shc are lean, resist obesity, have higher lipid oxidation capacity, and increased thiolase activity. The thiolase-p46Shc connection shown here in vitro and in organello may be an important underlying mechanism explaining the metabolic phenotype of Shc-depleted mice in vivo.

AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1) specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice. AAV1-Sirt1-treated mice showed up-regulated expression of key genes related to β-oxidation together with increased levels of phosphorylated AMP protein kinase. Moreover, SIRT1 overexpression in skeletal muscle also increased basal phosphorylated levels of AKT. However, AAV1-Sirt1 treatment was not enough to prevent high fat diet-induced obesity and insulin resistance. Although Sirt1 gene transfer to skeletal muscle induced changes at the muscular level related with lipid and glucose homeostasis, our data indicate that overexpression of SIRT1 in skeletal muscle is not enough to improve whole-body insulin resistance and that suggests that SIRT1 has to be increased in other metabolic tissues to prevent insulin resistance.

The relationship between Fibroblast Growth Factor-21 and characteristic parameters related to energy balance in dairy cows.

BackgroundNegative energy balance (NEB) is a common pathological foundation of ketosis and fatty liver. Liver and fat tissue are the major organs of lipid metabolism and take part in modulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB develop during perinatal period. Fibroblast growth factor-21 (FGF-21) is a recently discovered protein hormone that plays an important and specific regulating role in adipose lipid metabolism and liver gluconeogenesis for human and mouse. Our aim is to investigate the variation and relationship between serum FGF-21 concentration and characteristic parameters related to negative energy balance in different energy metabolism state.MethodsIn this research, five non-pregnant, non-lactating Holstein–Friesian dairy cows were randomly allocated into two groups. The interventions were a controlled-energy diet (30 % of maintenance energy requirements) and a moderate-energy diet (120 % of predicted energy requirements) that lasted for the duration of the experiment. We measured biochemical parameters, serum FGF-21, leptin and insulin levels by commercial ELISA kits.ResultsThe results showed that serum FGF-21 levels were significantly higher in both groups treated with a controlled-energy diet, while FGF-21 levels in both groups treated with moderate-energy diet were low. FGF-21 levels exhibited a significant positive correlation with serum leptin levels, while an inverse relationship was found between FGF-21 and blood glucose and β-hydroxybutyrate acid (BHBA) levels.ConclusionAn increase in FGF-21 levels after a controlled-energy diet treatment may contribute to a positive metabolic effect which could result in a new theoretical and practical basis for the preventive strategy of dairy cows with NEB.

Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes.

Circulating natriuretic peptide (NP) levels are reduced in obesity and predict the risk of type 2 diabetes (T2D). Since skeletal muscle was recently shown as a key target tissue of NP, we aimed to investigate muscle NP receptor (NPR) expression in the context of obesity and T2D. Muscle NPRA correlated positively with whole-body insulin sensitivity in humans and was strikingly downregulated in obese subjects and recovered in response to diet-induced weight loss. In addition, muscle NP clearance receptor (NPRC) increased in individuals with impaired glucose tolerance and T2D. Similar results were found in obese diabetic mice. Although no acute effect of brain NP (BNP) on insulin sensitivity was observed in lean mice, chronic BNP infusion improved blood glucose control and insulin sensitivity in skeletal muscle of obese and diabetic mice. This occurred in parallel with a reduced lipotoxic pressure in skeletal muscle due to an upregulation of lipid oxidative capacity. In addition, chronic NP treatment in human primary myotubes increased lipid oxidation in a PGC1α-dependent manner and reduced palmitate-induced lipotoxicity. Collectively, our data show that activation of NPRA signaling in skeletal muscle is important for the maintenance of long-term insulin sensitivity and has the potential to treat obesity-related metabolic disorders.

Glycemic Control, Skeletal Muscle Glucose Uptake And Lipid Metabolism In Mice With Skeletal Muscle Foxo1 Overexpression

Previous research has indicated a possible role for Forkhead Box protein O1 (FoxO1) in the pathogenesis of type 2 diabetes through its purported role in affecting whole body glycemic control and lipid metabolism. However, the literature indicating such a relationship is limited and has primarily relied on in vitro models. PURPOSE: The purpose of the present study was to use in vivo and ex vivo methodology to examine the role of FoxO1 on whole body glycemic control, skeletal muscle glucose metabolism and lipid metabolism. METHODS: Transgenic mice with skeletal muscle-specific overexpression of FoxO1 were subjected to intraperitoneal glucose tolerance testing (IPGTT) with concomitant plasma insulin analysis followed by ex vivo examination of skeletal muscle insulin stimulated glucose uptake, intramyocellular triglyceride (IMTG) storage and fatty acid oxidation. RESULTS: IPGTT and plasma insulin analysis revealed no differences between FoxO1 transgenic and wildtype (WT) mice. Likewise, basal level skeletal muscle protein expression levels of phosphoinositide kinase-3 (PI3K) and serine473 phosphorylated Akt (pAkt473) were not different between mouse strains. Additionally, FoxO1 did not exhibit any impairment in insulin stimulated glucose uptake. However, IMTG and fatty acid oxidation capacity was significantly (p<0.05) reduced in FoxO1 transgenic mice. CONCLUSION: These findings indicate that in vivo skeletal muscle FoxO1 overexpression does not impede whole body glycemic control or skeletal muscle insulin action. However, it does appear to reduce IMTG while impairing skeletal muscle lipid oxidation capacity.

Endurance Training Modulates Intramyocellular Lipid Compartmentalization and Morphology in Skeletal Muscle of Lean and Obese Women

The accumulation of intramyocellular lipids (IMCLs) and mitochondrial dysfunction in skeletal muscle have been associated with insulin resistance in obesity. Endurance training (ET) increases mitochondrial content/activity and IMCL content in young, active men and women. We have previously shown that ET alters the size, number, and physical juxtaposition of IMCLs and mitochondria. The purpose of this study was to determine the effects of obesity and ET on mitochondrial function, IMCL content, and IMCL-mitochondria juxtaposition in sedentary lean and obese women. DESIGN, SETTING, SUBJECTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Obese (n = 11) and lean (n = 12), sedentary women were recruited using local advertisements and underwent 12 weeks of ET in our training facility at McMaster University. Blood and muscle biopsy samples (vastus lateralis) were collected before and after ET to measure IMCL and mitochondrial ultrastructure, mitochondrial oxidative capacity, lipid oxidation capacity, and lipid metabolism by-products. Obese women were insulin resistant (homeostasis model assessment of insulin resistance) compared with lean women. ET did not change body weight but increased mitochondrial oxidative and β-oxidation capacity in both groups. ET mediated reorganization of the muscle architecture, whereby IMCL content in the subsarcolemmal region was reduced with a concomitant increase in intermyofibrillar IMCLs. ET increased the percentage of IMCLs in direct contact with mitochondria and did not alter diacylglycerol and ceramide content in either group. ET mediated positive changes in mitochondrial function and lipid oxidation and induced intracellular IMCL reorganization, which is reflective of greater IMCL turnover capacity in both lean and obese women.

Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents

Obesity is associated with poor fitness and adverse metabolic consequences in children. To investigate how exercise and lifestyle modification may improve fitness and insulin sensitivity in this population. Randomized controlled trial, 21 obese (body mass index ≥ 95% percentile) subjects, ages 10 to 17 years. Subjects were given standardized healthful lifestyle advice for 8 weeks. In addition, they were randomized to an in-home supervised exercise intervention (n = 10) or control group (n = 11). Fasting laboratory studies (insulin, glucose, lipid profile) and assessments of fitness, body composition, skeletal muscle oxidative phosphorylation and intramyocellular lipid content (IMCL), were performed at baseline and study completion. Subjects were 13.0 ± 1.9 (standard deviation) years old, 72% female and 44% non-white. Exercise improved fitness (P = 0.03) and power (P = 0.01), and increased IMCL (P = 0.02). HOMA-IR decreased among all subjects in response to lifestyle modification advice (P = 0.01), regardless of exercise training assignment. In univariate analysis in all subjects, change in cardiovascular fitness was associated with change in HOMA-IR. In exploratory analyses, increased IMCL was associated with greater resting energy expenditure (r = 0.78, P = 0.005) and a decrease in fasting respiratory quotient (r = -0.70, P = 0.02) (n = 11). Change in fitness was found to be related to change in insulin resistance in response to lifestyle modification and exercise in obese children. IMCL increased with exercise in these obese children, which may reflect greater muscle lipid oxidative capacity.

Metabolic flexibility and carnitine flux: The role of carnitine acyltransferase in glucose homeostasis

Metabolic flexibility and carnitine flux: The role of carnitine acyltransferase in glucose homeostasis

Enhanced Skeletal Muscle Lipid Oxidative Efficiency in Insulin-Resistant vs Insulin-Sensitive Nondiabetic, Nonobese Humans

Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals. The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals. In 13 insulin-sensitive [by Matsuda index (MI) (22.6 ± 0.6 [SE] kg/m(2)); 23 ± 1 years; MI 5.9 ± 0.1] and 13 insulin-resistant (23.2 ± 0.6 kg/m(2); 23 ± 3 years; MI 2.2 ± 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed. Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and β-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((14)CO2 and (14)C-acid soluble metabolites production) at 4 [1-(14)C]palmitate concentrations (45-520 μM) were also measured. None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 ± 0.4 vs 2.2 ± 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to (14)C-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 ± 0.04 vs 0.12 ± 0.02; P = .02). We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin resistance could be a potential mechanism to prevent further lipotoxicity.

Cardiac Molecular-Acclimation Mechanisms in Response to Swimming-Induced Exercise in Atlantic Salmon

Cardiac muscle is a principal target organ for exercise-induced acclimation mechanisms in fish and mammals, given that sustained aerobic exercise training improves cardiac output. Yet, the molecular mechanisms underlying such cardiac acclimation have been scarcely investigated in teleosts. Consequently, we studied mechanisms related to cardiac growth, contractility, vascularization, energy metabolism and myokine production in Atlantic salmon pre-smolts resulting from 10 weeks exercise-training at three different swimming intensities: 0.32 (control), 0.65 (medium intensity) and 1.31 (high intensity) body lengths s−1. Cardiac responses were characterized using growth, immunofluorescence and qPCR analysis of a large number of target genes encoding proteins with significant and well-characterized function. The overall stimulatory effect of exercise on cardiac muscle was dependent on training intensity, with changes elicited by high intensity training being of greater magnitude than either medium intensity or control. Higher protein levels of PCNA were indicative of cardiac growth being driven by cardiomyocyte hyperplasia, while elevated cardiac mRNA levels of MEF2C, GATA4 and ACTA1 suggested cardiomyocyte hypertrophy. In addition, up-regulation of EC coupling-related genes suggested that exercised hearts may have improved contractile function, while higher mRNA levels of EPO and VEGF were suggestive of a more efficient oxygen supply network. Furthermore, higher mRNA levels of PPARα, PGC1α and CPT1 all suggested a higher capacity for lipid oxidation, which along with a significant enlargement of mitochondrial size in cardiac myocytes of the compact layer of fish exercised at high intensity, suggested an enhanced energetic support system. Training also elevated transcription of a set of myokines and other gene products related to the inflammatory process, such as TNFα, NFκB, COX2, IL1RA and TNF decoy receptor. This study provides the first characterization of the underlying molecular acclimation mechanisms in the heart of exercise-trained fish, which resemble those reported for mammalian physiological cardiac growth.

Acute exercise reverses starvation-mediated insulin resistance in humans

Within 2-3 days of starvation, pronounced insulin resistance develops, possibly mediated by increased lipid load. Here, we show that one exercise bout increases mitochondrial fatty acid (FA) oxidation and reverses starvation-induced insulin resistance. Nine healthy subjects underwent 75-h starvation on two occasions: with no exercise (NE) or with one exercise session at the end of the starvation period (EX). Muscle biopsies were analyzed for mitochondrial function, contents of glycogen, and phosphorylation of regulatory proteins. Glucose tolerance and insulin sensitivity, measured with an intravenous glucose tolerance test (IVGTT), were impaired after starvation, but in EX the response was attenuated or abolished. Glycogen stores were reduced, and plasma FA was increased in both conditions, with a more pronounced effect in EX. After starvation, mitochondrial respiration decreased with complex I substrate (NE and EX), but in EX there was an increased respiration with complex I + II substrate. EX altered regulatory proteins associated with increases in glucose disposal (decreased phosphorylation of glycogen synthase), glucose transport (increased phosphorylation of Akt substrate of 160 kDa), and FA oxidation (increased phosphorylation of acetyl-CoA carboxylase). In conclusion, exercise reversed starvation-induced insulin resistance and was accompanied by reduced glycogen stores, increased lipid oxidation capacity, and activation of signaling proteins involved in glucose transport and FA metabolism.

Aerobic physical training after weaning improves liver histological and metabolic characteristics of diet-induced obese rats

Summary Objectives To evaluate liver mitochondrial function and its impacts on fat liver accumulation and the effects of the physical training in cafeteria diet feeding rats. Methods Control (C), sedentary cafeteria diet rats (DIO), and trained cafeteria diet rats (TDIO) accompanied from 21 days old to 120 days old were submitted to body weight and adiposity analysis, glycemic and lipid profile, liver histology, liver mitochondrial analysis (lipid oxidation and phosphorylation capacity). Results DIO presented elevated body weight and adiposity, and aerobic training (TDIO) improved these parameters. TDIO showed reduced triglycerides and LDL-cholesterol and elevated HDL-cholesterol. DIO presented higher fat liver accumulation that was reversed in TDIO. Liver mitochondria from DIO exhibited a higher β-oxidation capacity and an increase in the capacity of oxidizing succinate, with little effects of physical exercise. Our results demonstrated that in DIO, the development of steatosis preceded the establishment of body insulin resistance, which, in turn, has been considered the “first hit” in hepatic steatosis development. These suggest that some intrahepatic events could arise very early in conditions of poor nutrition and probably contribute to the development of NAFLD. Then, our results suggest that starting physical activity just after weaning decreased adverse effects of cafeteria diet on body composition, lipid profile, and liver fat deposition.

Site E14 in Hemoglobins and Myoglobins: A Key Residue That Affects Hemin Loss and Lipid Oxidation Capacity

Fish hemoglobins (Hbs) frequently contain glycine at site E14 while mammalian Hbs contain larger residues (e.g., alanine and serine). These differences were examined by creating structural variants at E14 using recombinant bovine myoglobin (Mb) as a model heme protein that contains alanine at E14. The Ala(E14)Gly mutation increased k(ox) and hemin loss 3-fold and 45-fold, respectively. Glycine at E14 creates a channel for solvent to enter the heme crevice, which enhances autoxidation and hemin loss rates. Hydration of the proximal heme pocket facilitates hemin loss because protonation of the proximal histidine weakens the linkage of the imidazole group to the iron atom of the hemin moiety. Ala(E14)Gly promoted lipid oxidation in washed fish muscle more rapidly during iced storage compared to wild type Mb at pH 5.7. This suggested that the rapid hemin loss from Ala(E14)Gly accelerated lipid oxidation. Ala(E14)Ser and Ala(E14)Val had little effect on k(ox) but somewhat accelerated net hemin loss. These studies suggest that enhanced access of solvent to the heme crevice of many fish Hbs at site E14 facilitates rapid hemin loss and moderately accelerates autoxidation. This likely is part of the reason fish Hbs promote lipid oxidation much more effectively compared to mammalian Hbs.

Impact of food matrix on isoflavone metabolism and cardiovascular biomarkers in adults with hypercholesterolemia

The role of food matrix and gender on soy isoflavone metabolism and biomarkers of activity were examined in twenty free-living adults (34.7 ± 11.5 years old) with hypercholesterolemia (221.9 ± 18.7mg dL(-1)). In a randomized crossover design study, participants consumed soy bread (3 wk) or a soy beverage (3 wk) containing 20 g soy protein with 99 and 93 mg isoflavones aglycone equivalents per day, respectively. During soy bread intervention, women had significantly greater microbial metabolite excretion (P = 0.05) of isoflavonoids than men. In men, isoflavone metabolite excretion was not discernibly different between the two matrices. Significant reductions (P≤ 0.05) in triglycerides (24.8%), LDL cholesterol (6.0%), apolipoprotein A-I (12.3%), and lipid oxidative stress capacity (25.5%), were observed after soy food intervention. Our findings suggest that the food matrix significantly impacts soy isoflavone metabolism, particularly microbial metabolites in women.

The Metabolically Benign and Malignant Fatty Liver

The epidemics of the major metabolic diseases type 2 diabetes and cardiovascular disease are increasing worldwide and much effort is being undertaken to understand the pathogenesis of these conditions. Both type 2 diabetes and cardiovascular disease share insulin resistance as a common and important risk factor in their natural history. It is now widely accepted that organ cross talk harbors many critical clues that help to better understand the pathogenesis of insulin resistance. In this respect, several studies recently showed that not the increase in body fat mass per se, but the accumulation of fat in the visceral cavity and particularly in the liver, which are conditions commonly accompanied by inflammatory processes, are responsible for the genesis of insulin resistance (1–4). ### Prevalence, pathogenesis, and progression. The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide, affecting more than 25% of adults. In obese people and in patients with type 2 diabetes, the prevalence has increased to more than 70%. In obese children, NAFLD is found in 23–53% (5). Several mechanisms lead to fatty liver. First, expansion and inflammation of adipose tissue results in adipose insulin resistance and increased lipolysis and thereby in an elevated flux of free fatty acids into the liver. Second, an impaired hepatic fatty acid oxidation and a decrease in proteins inducing lipid oxidation, e.g., adiponectin, results in further accumulation of fat within the liver. Third, increased hepatic de novo lipogenesis driven by hyperinsulinemia and increased carbohydrate intake elevate the hepatic fat content. Fourth, impaired VLDL secretion exacerbates this process. This stage is often referred to as benign steatosis. The overwhelming of lipid oxidation capacity eventually occurs resulting in the generation of reactive oxidative species (ROS), gut-derived signals (e.g., bacterial endotoxins, short-chain fatty acids), inflammatory cytokines, and an imbalanced release of adipokines that then may result …