Levels Of Fatty Acid Synthesis Research Articles

Coated sodium butyrate ameliorates high-energy and low-protein diet induced hepatic dysfunction via modulating mitochondrial dynamics, autophagy and apoptosis in laying hens

BackgroundFatty liver hemorrhagic syndrome (FLHS), a fatty liver disease in laying hens, poses a grave threat to the layer industry, stemming from its ability to trigger an alarming plummet in egg production and usher in acute mortality among laying hens. Increasing evidence suggests that the onset and progression of fatty liver was closely related to mitochondria dysfunction. Sodium butyrate was demonstrated to modulate hepatic lipid metabolism, alleviate oxidative stress and improve mitochondrial dysfunction in vitro and mice models. Nevertheless, there is limited existing research on coated sodium butyrate (CSB) to prevent FLHS in laying hens, and whether and how CSB exerts the anti-FLHS effect still needs to be explored. In this experiment, the FLHS model was induced by administering a high-energy low-protein (HELP) diet in laying hens. The objective was to investigate the effects of CSB on alleviating FLHS with a focus on the role of CSB in modulating mitochondrial function.MethodsA total of 288 healthy 28-week-old Huafeng laying hens were arbitrarily allocated into 4 groups with 6 replicates each, namely, the CON group (normal diet), HELP group (HELP diet), CH500 group (500 mg/kg CSB added to HELP diet) and CH750 group (750 mg/kg CSB added to HELP diet). The duration of the trial encompassed a period of 10 weeks.ResultsThe result revealed that CSB ameliorated the HELP-induced FLHS by improving hepatic steatosis and pathological damage, reducing the gene levels of fatty acid synthesis, and promoting the mRNA levels of key enzymes of fatty acid catabolism. CSB reduced oxidative stress induced by the HELP diet, upregulated the activity of GSH-Px and SOD, and decreased the content of MDA and ROS. CSB also mitigated the HELP diet-induced inflammatory response by blocking TNF-α, IL-1β, and F4/80. In addition, dietary CSB supplementation attenuated HELP-induced activation of the mitochondrial unfolded protein response (UPRmt), mitochondrial damage, and decline of ATPase activity. HELP diet decreased the autophagosome formation, and downregulated LC3B but upregulated p62 protein expression, which CSB administration reversed. CSB reduced HELP-induced apoptosis, as indicated by decreases in the Bax/Bcl-2, Caspase-9, Caspase-3, and Cyt C expression levels.ConclusionsDietary CSB could ameliorate HELP diet-induced hepatic dysfunction via modulating mitochondrial dynamics, autophagy, and apoptosis in laying hens. Consequently, CSB, as a feed additive, exhibited the capacity to prevent FLHS by modulating autophagy and lipid metabolism.Graphical

Inhibition of lipid synthesis by the HIV integrase strand transfer inhibitor elvitegravir in primary rat oligodendrocyte cultures.

Combined antiretroviral therapy (cART) has greatly decreased mortality and morbidity among persons with HIV; however, neurologic impairments remain prevalent, in particular HIV-associated neurocognitive disorders (HANDs). White matter damage persists in cART-treated persons with HIV and may contribute to neurocognitive dysfunction as the lipid-rich myelin membrane of oligodendrocytes is essential for efficient nerve conduction. Because of the importance of lipids to proper myelination, we examined the regulation of lipid synthesis in oligodendrocyte cultures exposed to the integrase strand transfer inhibitor elvitegravir (EVG), which is administered to persons with HIV as part of their initial regimen. We show that protein levels of genes involved in the fatty acid pathway were reduced, which correlated with greatly diminished de novo levels of fatty acid synthesis. In addition, major regulators of cellular lipid metabolism, the sterol regulatory element-binding proteins (SREBP) 1 and 2, were strikingly altered following exposure to EVG. Impaired oligodendrocyte differentiation manifested as a marked reduction in mature oligodendrocytes. Interestingly, most of these deleterious effects could be prevented by adding serum albumin, a clinically approved neuroprotectant. These new findings, together with our previous study, strengthen the possibility that antiretroviral therapy, at least partially through lipid dysregulation, may contribute to the persistence of white matter changes observed in persons with HIV and that some antiretrovirals may be preferable as life-long therapy.

P-543 Higher maternal age alters the insulin/IGF system and intracellular lipid metabolism of the endometrium and in the preimplantation embryo – insights from the rabbit model.

Abstract Study question Our aim was to analyse the embryo-maternal-interaction, focusing on the insulin/IGF-system and lipid metabolism on day 6 of pregnancy in reproductive young and old rabbits. Summary answer Advanced maternal age has a decisive effect on maternal and embryonic insulin/IGF-signalling and lipid metabolism, leading to higher embryo loss already during preimplantation period. What is known already The reproductive potential in women declines with age. Molecular and biochemical mechanisms involved in age-related infertility and their impact on embryo-maternal-interaction during early pregnancy are still not completely understood. However, establishment of a successful pregnancy depends on the physiological condition of the mother and a continuous dialogue with the developing embryo. The insulin/IGF-system plays a pivotal role in this embryo-maternal crosstalk, connecting maternal insulin/IGF with embryonic metabolism, cell proliferation and differentiation. Study design, size, duration We used the rabbit as reproductive model to investigate maternal age-related alterations in embryo-maternal-interaction during preimplantation period. Compared to humans, the rabbit shares high similarities in early embryo development, gastrulation and lipid metabolism (DOI: 10.1530/REP-12-0091 and DOI: 10.1093/ajcn/62.2.458S). A total of 50 young (16-20 weeks) and 31 old (<108 weeks) sexually mature, female rabbits were used for analysis at day 6 post coitum. Participants/materials, setting, methods We measured mRNA and protein levels of target genes of the insulin/IGF system and lipid metabolism by quantitative PCR, Western Blot and ELISA. Therefore, maternal blood, endometrium and blastocysts were analysed from reproductive young (16 to 20 weeks) and old (over 108 weeks) rabbits on day 6 of pregnancy. Blastocysts and ovulation points were counted and only blastocysts at the pre-gastrulating stage 1, separated in embryoblast (EB) and trophoblast (TB), were used for further analyses. Main results and the role of chance At day 6 of pregnancy, reproductive old rabbits had a lower amount of embryos. Maternal serum insulin and IGF levels were reduced in reproductive old rabbits, accompanied by a paracrine upregulation of IGF1 and its receptors in the endometrium. Preimplantation blastocysts adapted to hormonal changes by reducing IGF1 and IGF2 levels in both embryonic compartments, EB and TB, while the expression of embryonic IGF receptors was unchanged. Furthermore, an increase of fatty acids metabolism was observed in the ageing endometrium, indicated by the higher level of carnitine palmitoyltransferase I B (CPT1B) and elevated expression of fatty acid binding and transport proteins. These results are in line with lower level of fatty acid synthesis (FASN) in the endometrium from old, gravid rabbits, the key enzyme of fatty acid synthesis. Embryonic fatty acid uptake and b-oxidation were increased in EB and TB, too. The observed changes in embryonic and maternal lipid metabolism are caused by the alterations of the transcription factors cAMP-responsive element binding protein (CREB) and peroxisome proliferator-activated receptor (PPAR) α and γ in endometrium and embryos from reproductive old rabbits. Limitations, reasons for caution Rabbit embryogenesis reflects human development only during blastocysts formation. Therefore, statements are limited to the embryogenesis stages investigated. Wider implications of the findings The results of the current study are in accordance with the common literature, showing that advanced maternal age affects developmental competence of embryos. Our study points out that advanced maternal age alters lipid metabolism and insulin/IGF-signalling, which are two crucial components in embryo-maternal-interaction. Trial registration number not applicable

Dietary Coated Sodium Butyrate Ameliorates Hepatic Lipid Accumulation and Inflammation via Enhancing Antioxidative Function in Post-Peaking Laying Hens.

During the aging process of laying hens, hepatic oxidative stress damage and lipid accumulation are prone to occur, leading to the deterioration of egg quality and a decline in production properties. This research was designed to explore the effects of different levels of coated sodium butyrate (CSB) addition on oxidation resistance, inflammatory reaction, lipid metabolism and hepatic oxidative damage-related gene expression in aged laying hens. A total of 720 healthy 52 weeks old Huafeng laying hens were arbitrarily divided into 5 groups of 6 replicates with 24 birds each and fed a basal diet supplemented with 0, 250, 500, 750 and 1000 mg/kg CSB for 8 weeks, respectively. The CSB quadratically upgraded GSH-Px activities and downgraded MDA content in the liver and serum. The LDL-C, NEFA and TG contents decreased quadratically in CSB groups and significantly reduced the fatty vacuoles as well as the formation of fat granules in the liver (p < 0.05). Meanwhile, the CSB quadratically upregulated the gene expression of IL-10, Nrf2 and HO1, but downregulated the gene expression of IFN-γ, TNF-α and Keap1 in a quadratic manner (p < 0.05). Moreover, the CSB quadratically degraded the mRNA level of fatty acid synthesis but increased the gene level of key enzymes of fatty acid catabolism (p < 0.05). In conclusion, dietary CSB supplementation has a favorable effect in protecting against liver injury and alleviating lipid accumulation and inflammation by enhancing hepatic antioxidative function in aged laying hens.

Diospyros kaki and Citrus unshiu Mixture Improves Disorders of Lipid Metabolism in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) has been a major cause of a chronic liver disease over recent decades and increasing worldwide in parallel with the remarkable growth of obesity. In the present study, we investigate the ameliorative effects of PCM, a combination of Diospyros kaki fruit and Citrus unshiu peel mixture, on high-fat diet- (HFD-) induced NAFLD and clarify the potential mechanisms. PCM in HFD-fed mice was orally administered at a dose of 50 or 100 mg/kg subsequently for 2 months. Thereafter, lipid metabolism parameters and fat synthesis-related genes in the mouse liver were evaluated. Subsequently, body weight changes, liver weight, serum liver function and lipid profiles, and liver pathology were examined, and the relative levels of fatty acid synthesis and β-oxidation gene expression were evaluated by western blot. Serum AST, ALT, and TG levels in the HFD control mice were significantly higher than those of normal mice. Compared with HFD control mice, PCM supplementation increased phosphorylation of AMP-activated protein kinase (AMPK). Peroxisome proliferator-activated receptor (PPAR) α was significantly increased by PCM administration. Continuously, the activation of PPARα significantly elevated carnitine palmitoyltransferase 1 (CPT-1), a key enzyme in fatty acid β-oxidation, and mitochondrial uncoupling protein 2 (UCP-2), thermogenic regulatory genes, in PCM-treated mice compared with those of HFD control mice. Moreover, PCM inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 and its target genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Taken together, these effects were mediated through activation of AMPK. In the conclusion, PCM improved liver damage in HFD-fed mice and attenuated NAFLD by the activation of PPARα and the inhibition of SREBPs expression via AMPK-dependent pathways.

Dissimilar regulation of glucose and lipid metabolism by leptin in two strains of gibel carp (Carassius gibelio).

Previous nutritional studies have shown that insulin regulation is different between DT and A strains of gibel carp. As leptin plays a pivotal role in the effects of insulin, we hypothesised that leptin regulation of glucose and lipid metabolism would differ between the two strains. To test our hypothesis, recombinant human leptin was injected into two strains. The results showed that leptin activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), AMP-activated protein kinase-acetyl coenzyme A carboxylase and Janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) signalling pathways in both strains. Hypoglycaemia induced by leptin might be due to higher glucose uptake by the liver and muscles together with enhanced glycolytic potential and reduced gluconeogenic potential. Decreased lipogenesis and up-regulated fatty acid oxidation were induced by leptin. In terms of genotype, the PI3K-AKT signalling pathway was more strongly activated by leptin in the muscle tissue of the A strain, as reflected by the heightened phosphorylation of AKT. Furthermore, glycogen content, glycolytic enzyme activity and gluconeogenic capability were higher in the A strain than the DT strain. Strain A had higher levels of fatty acid synthesis and lipolytic capacity in the liver than the DT strain, but the opposite was true in white muscle. Regarding leptin-genotype interactions, the DT strain displayed stronger regulation of glucose metabolism in the liver by leptin as compared with the A strain. Moreover, a more active JAK2-STAT signalling pathway accompanied by enhanced inhibition of fatty acid synthesis by leptin was observed in the DT strain. Overall, the regulation of glucose and lipid metabolism by leptin differed between the two strains, as expected.

Dietary Lycium barbarum extract administration improved growth, meat quality and lipid metabolism in hybrid grouper (Epinephelus lanceolatus ♂ × E. fuscoguttatus ♀) fed high lipid diets

Growth, plasma biochemical parameters, meat quality, and expressions of lipid metabolism related genes were investigated in hybrid grouper fed high lipid diets supplemented with five levels (0, 0.5, 1, 2 and 10 g kg−1) of Lycium barbarum extract (LBE) for 8 weeks. Results showed that dietary LBE significantly improved growth and protein deposition, but reduced hepatic lipid content and abdominal fat percentage. Meanwhile, dietary LBE decreased plasma cholesterol, triglyceride and low density lipoprotein cholesterol contents, but improved the meat composition, amino acids and fatty acids profile in the muscle. Moreover, dietary LBE supplementation significantly increased the expression levels of hepatic fatty acid catabolism related genes, but reduced the expression levels of fatty acid synthesis and uptake related genes except for fish fed diets containing 4 g kg−1 LBE. In conclusion, dietary supplementation of LBE at 0.5–10 g kg−1 improved growth, protein deposition, meat quality and lipid metabolism in fish fed high lipid diets.

THE SEASONAL EFFECTS ON IMF CONTENT OF FAS mRNA EXPRESION IN MUSCLES OF MONGOLIAN SHEEP

This survey’s aim was to investigate the seasonal effect of Fatty acid synthesis (FAS) expression on intramuscular fat (IMF) content in grazing Mongolian, Ujumqin and grain-fed Ujumqin sheep. Different skeletal muscles of sheep (biceps femoris, longissimus dorsi and triceps brachii) were sampled to measure IMF content and total RNA was extracted to determine FAS mRNA expression levels by real-time PCR. The result revealed that: (1) The difference in IMF content in the muscles of Mongolian sheep grazed in summer was observed to be much higher than sheep grazed in winter (p&lt;0.01). Also there was significant difference in IMF content in the muscles of Ujumqin sheep grazed in summer than winter (p&lt;0.05). The mRNA expression level of FAS in muscles of winter grazing Mongolian sheep was significantly higher than summer (p&lt;0.05). The seasonal effects on IMF content in the muscles and it’s FAS mRNA gene expression was all negative correlated between the sheep breeds. Accordingly, grazing Mongolian sheep’s FAS gene expression level was very high negatively correlated (r=-0.964). This study suggested that grazing Mongolian and Ujumqin sheep able to store large amount of IMF under depends on seasonal effects.

Formaldehyde alters triglyceride synthesis and very low-density lipoprotein secretion in a time-dependent manner

Formaldehyde is a common indoor air pollutant that is toxic to the liver. This study aimed to investigate the effects of formaldehyde on triglyceride metabolism in human hepatocellular carcinoma cells (HepG2). Cell viability was detected using a MTT (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide) assay. Following treatment with different concentrations of formaldehyde for 24 and 48h, the intra and extra-hepatocellular triglyceride (TG) content was determined using a chemical-enzymatic method; Western blotting was used to detect the levels of fatty acid synthesis and VLDL-related proteins. Our results showed that cell viability significantly decreased after formaldehyde treatment (0.5–12.5mM, 24/48h). Extracellular TG levels in the hepatocytes increased after formaldehyde treatment at 0.004mM–0.1mM for 24h. SREBP-1c, ACC, FASN, and MTP, CES3 and DGAT1 proteins increased significantly after 24h of formaldehyde treatment. Intracellular TG levels decreased for 48h treatment of formaldehyde. AMPKα increased significantly in all tested groups and p-AMPK increased significantly after 0.1mM formaldehyde treatment for 48h. Our results indicated that short–term formaldehyde exposure balances triglyceride metabolism by promoting hepatocellular TG synthesis and VLDL secretion; Long-term formaldehyde disturbs the TG metabolism balance in the hepatocytes.

High-Intensity Aerobic Exercise Improves Both Hepatic Fat Content and Stiffness in Sedentary Obese Men with Nonalcoholic Fatty Liver Disease

We compared the effects of 12-week programs of resistance training (RT), high-intensity interval aerobic training (HIAT), and moderate-intensity continuous aerobic training (MICT). The primary goal was to evaluate the therapeutic effects of the exercise modalities for the management of nonalcoholic fatty liver disease (NAFLD). A total of 61 sedentary obese men with NAFLD were randomized into one of the following exercise regimens (RT, HIAT, or MICT). Hepatic fat content was decreased to a similar extent in the RT, HIAT, and MICT groups (−14.3% vs. −13.7% vs. −14.3%) without significant changes in weight and visceral fat. The gene expression levels of fatty acid synthesis were significantly decreased in the subjects’ monocytes. Hepatic stiffness was decreased only in the HIAT group (−16.8%). The stiffness change was associated with restored Kupffer cell phagocytic function (+17.8%) and decreased levels of inflammation such as leptin (−13.2%) and ferritin (−14.1%). RT, HIAT, and MICT were equally effective in reducing hepatic fat content, but only HIAT was effective in improving hepatic stiffness and restoring Kupffer cell function. These benefits appeared to be independent of detectable weight and visceral fat reductions; the benefits were acquired through the modulation of in vivo fatty acid metabolism and obesity-related inflammatory conditions.

Prevention and treatment effect of total flavonoids in Stellera chamaejasme L. on nonalcoholic fatty liver in rats.

BackgroundThe incidence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide in parallel with the obesity epidemic. This study aims to investigate the effects of the total flavonoids in Stellera chamaejasme L. (TFSC) on the experimental NAFLD in high fat diet fed (HFD) rats.MethodsNAFLD model was induced in male Wistar rats by high-fat diet, and the rats in NAFLD group were randomized into NAFLD group (n = 20) and TFSC-treated group (n = 60). Both groups were given high-fat diet, and the normal group (n = 20) was given normal diet. In addition, the TFSC treated group was administered TFSC orally once a day at a low dose of 100 mg/kg (n = 20), medium dose of 200 mg/kg (n = 20), and high dose of 400 mg/kg (n = 20) for 6 weeks. Subsequently, the rats were sacrificed and body weight changes, lipid profiles in plasma and liver pathology were examined. The relative levels of fatty acid synthesis and β-oxidation gene expression in hepatic tissues were measured by quantitative real-time polymerase chain reaction (RT-PCR).ResultsAfter the HFD administration for 4 weeks, the body weight,serum TC and TG levels in the rat of model group were significantly higher than in normal group (P < 0.05), and which Showed that the experimental NAFLD model was successfully established. While continual feeding with HFD deteriorated NAFLD and hyperlipidemia, and treatment with the different doses of TFSC effectively improved serum and liver lipid metabolism and liver function. A linear relationship between the dose of TFSC and blood lipid level was observed. The mRNA expression of hepatic acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), Leptin (LEP) and sterol regulatory element binding protein (SREBP)-1c as well as peroxisome proliferator-activated receptor (PPAR) –γ were significantly lower in high-dose group compared to the positive control group (P < 0.05). The hepatic mRNA expression of Cholesterol 7α-hydroxylase1 (CYP7A1), Carnitine palmitoyltransferase-1 (CPT1) and peroxisome proliferator-activated receptor (PPAR) –α were significantly higher in the high-dose group compared to the positive control group (P < 0.05). However, no difference was detected in the middle-dose group or the low-dose group compared to the positive control group (P > 0.05).ConclusionTFSC treatment effectively improved NAFLD-related hyperlipidemia and inhibited liver steatosis in rats, and accompanied by modulating the expression of genes for regulating lipid metabolism.

The effect of calving in the summer on the hepatic transcriptome of Holstein cows during the peripartal period

The liver is the main metabolic organ coordinating the adaptations that take place during the peripartal period of dairy cows. A successful transition into lactation, rather than management practices alone, depends on environmental factors such as temperature, season of parturition, and photoperiod. Therefore, we analyzed the effect of calving season on the hepatic transcriptome of dairy cows during the transition period. A total of 12 Holstein dairy cows were assigned into 2 groups based on calving season (6 cows March–April, spring; 6 cows June–July, summer, SU). The RNA was extracted from liver samples obtained at −30, 3, and 35 DIM via percutaneous biopsy and hybridized to the Agilent 44K Bovine (V2) Gene Expression Microarray (Agilent Technologies Inc., Santa Clara, CA). A quantitative PCR on 22 target genes was performed to verify and expand the analyses. A total of 4,307 differentially expressed genes were detected (false discovery rate ≤0.05) in SU compared with spring. Furthermore, 73 unique differentially expressed genes were detected in SU compared with spring cows after applying a fold-change threshold ≥3 and ≤−3. For Kyoto Encyclopedia of Genes and Genomes pathways analysis of differentially expressed genes, we used the dynamic impact approach. Ingenuity Pathway Analysis software was used to analyze upstream transcription regulators and perform gene network analysis. Among metabolic pathways, energy metabolism from lipids, carbohydrates, and amino acids was strongly affected by calving in SU, with a reduced level of fatty acid synthesis, oxidation, re-esterification, and synthesis of lipoproteins, leading to hepatic lipidosis. Glycan-synthesis was downregulated in SU cows probably as a mechanism to counteract the progression of this lipidosis. In contrast, calving in the SU resulted in upregulation of gluconeogenesis but also greater use of glucose as an energy source. Among nonmetabolic pathways, the heat-shock response was obviously activated in SU cows but was also associated with inflammatory and intracellular stress response. Furthermore, data support a recent finding that cows experience endoplasmic reticulum stress around parturition. Transcription regulator analysis revealed how metabolic changes are related to important regulatory mechanisms, including epigenetic modification. The holistic analyses of the liver transcriptome response to calving in the summer at high environmental temperatures underscore how transition cows should be carefully managed during this period, as they experience alterations in liver energy metabolism and inflammatory state increasing susceptibility to health disorders in early postpartum.

분화된 3T3-L1 세포에서 잣송이 초임계 추출물의 지방분해 효과

Seeds of Korean pine cone (Pinus koraiensis) have long been consumed as an edible food in countries located in North-East Asia, On the other hand, Korean pine cone, containing various polyphenols, is discarded as a useless garbage after removing seeds. This study investigated the lipolytic effects of pine cone extract in differentiated 3T3-L1 adipocytes. Intracellular lipid accumulation was measured by Oil red O staining, free glycerol release by colorimetric reaction, and expression of genes related to lipid metabolism by real-time PCR. Compared to control, pine cone extract reduced intracellular lipid accumulation by 8.8% and increased free glycerol release by 8.2% a concentration of 5 μg/mL in differentiated 3T3-L1 adipocytes. mRNA levels of fatty acid synthesis were not significantly different between control and pine cone extract, but mRNA levels of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) significantly increased by 38.7% and 94.1% at a concentration of 5 μg/mL, respectively. Thus, pine cone extract is suggested to have lipolytic effects through induction of LPL and HSL gene expression.

Expression of genes associated with fatty acid metabolism during maturation in diploid and triploid female rainbow trout

Abstract To study the effects of sexual maturation on fatty acid metabolism in fish fed to satiation daily, expression of thirty-five genes involved in fatty acid metabolism was determined in sexually maturing diploid (2N; fertile) and triploid (3N; sterile) female rainbow trout. Gene expression was assessed in liver, white muscle, and visceral adipose tissues for fish that were 16 to 24 M of age. Previously, we reported minimal differences in most growth measurements between maturing 2N and 3N fish, but there were disparate changes in muscle proximate composition, visceral fat stores, and fatty acid contents of energy stores at 21 M with 3N females having greater lipid stores. Here, we report that gene expression profiles of liver and white muscle corresponded to the phenotypes with significant differences in expression at 20 M. Triploid females had increased expression of genes involved in fatty acid synthesis; including gpat , srebp1 , acyl , acc , fas , and scd1 in liver and fas in muscle. Conversely, 2N muscle had increased expression of β-oxidation genes cpt1b , cpt2 , ehhadh , and acat2 and TORC1 inhibitors redd1 , erk , mo25 , and pras40 . Diploid muscle also had increased expression of pparβ along with increased expression of the fatty acid transporter gene cd36 , and β-oxidation genes cpt1a , cpt1c , aco , and acdhvl at 20 M. Additionally, 2N visceral adipose tissue had increased cpt1a expression at 21 M. Overall, data suggest that 3N females are undergoing higher levels of fatty acid synthesis while 2N females have higher levels of β-oxidation during sexual maturation. Phenotypic data supports these findings with decreasing fatty acid stores in 2N females during this time period. Additionally, changes in gene expression are associated with altered expression within the mTOR and PPARβ signaling pathways.

Can Behenic Acid (C22:0) Levels be a Prognostic Factor in Glial Tumors?

Inhibition of fatty acid synthase leads to apoptosis in cancers, which leads to high levels of fatty acid synthesis. This indicates that cancer cells depend on fatty acid in order to survive. In this study, we investigated whether or not there was a relationship between the glial tumor grade and free fatty acid level of tumor tissue. Twenty patients who had high grade glial tumors and 20 patients who had low grade glial tumors, were included in the study. Tumors samples were obtained intraoperatively in order to measure the fatty acid levels. The fatty acids were studied in three groups: saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. They were analyzed with gas chromatography. The oleic acid, linoleic acid, eicosadienoic acid, arachidonic acid, and docosadienoic acid levels were high in the tumor tissue of low grade tumors. The myristic acid, palmitic acid, stearic acid, alpha linoleic acid, eicosenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, and ceramide levels were high in the tumor tissue of high grade glial tumors. However, none of these high values were statistically significant. The high values of behenic acid, a saturated fatty acid, in low grade glial tumors were statistically significant. High levels of behenic acid in patients with low grade glial tumor is important as it indicates persistence of the tissue integrity and tissue resistance. behenic acid levels can be a prognostic factor in glial tumors.

Comparison of Dietary Control and Atorvastatin on High Fat Diet Induced Hepatic Steatosis and Hyperlipidemia in Rats

BackgroundTreatment with atorvastatin (ATO) or dietary control has been demonstrated to benefit patients with non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia. However, little is known on whether combination of dietary control and ATO treatment could enhance the therapeutic effect.MethodsWe employed a rat model of NAFLD to examine the therapeutic efficacy of dietary control and/or ATO treatment. Sprague-Dawley rats were fed with normal chow diet as normal controls or with high fat diet (HFD) for 12 weeks to establish NAFLD. The NAFLD rats were randomized and continually fed with HFD, with normal chow diet, with HFD and treated with 30 mg/kg of ATO or with normal chow diet and treated with the same dose of ATO for 8 weeks. Subsequently, the rats were sacrificed and the serum lipids, aminotranferase, hepatic lipids, and liver pathology were characterized. The relative levels of fatty acid synthesis and β-oxidation gene expression in hepatic tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hepatic expression of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was determined by Western blot assay.ResultsWhile continual feeding with HFD deteriorated NAFLD and hyperlipidemia, treatment with dietary control, ATO or ATO with dietary control effectively improved serum and liver lipid metabolism and liver function. In comparison with ATO treatment, dietary control or combined with ATO treatment significantly reduced the liver weight and attenuated the HFD-induced hyperlipidemia and liver steatosis in rats. Compared to ATO treatment or dietary control, combination of ATO and dietary control significantly reduced the levels of serum total cholesterol and low density lipoprotein cholesterol (LDL-C). However, the combination therapy did not significantly improve triglyceride and free fatty acid metabolism, hepatic steatosis, and liver function, as compared with dietary control alone.ConclusionsATO treatment effectively improved NAFLD-related hyperlipidemia and inhibited liver steatosis, accompanied by modulating the expression of genes for regulating lipid metabolism. ATO enhanced the effect of dietary control on reducing the levels of serum total cholesterol and LDL-C, but not triglyceride, free fatty acid and hepatic steatosis in HFD-induced fatty liver and hyperlipidemia in rats.

Sources of NADPH and Expression of Mammalian NADP+-specific Isocitrate Dehydrogenases in Saccharomyces cerevisiae

To compare roles of specific enzymes in supply of NADPH for cellular biosynthesis, collections of yeast mutants were constructed by gene disruptions and matings. These mutants include haploid strains containing all possible combinations of deletions in yeast genes encoding three differentially compartmentalized isozymes of NADP+-specific isocitrate dehydrogenase and in the gene encoding glucose-6-phosphate dehydrogenase (Zwf1p). Growth phenotype analyses of the mutants indicate that either cytosolic NADP+-specific isocitrate dehydrogenase (Idp2p) or the hexose monophosphate shunt is essential for growth with fatty acids as carbon sources and for sporulation of diploid strains, a condition associated with high levels of fatty acid synthesis. No new biosynthetic roles were identified for mitochondrial (Idp1p) or peroxisomal (Idp3p) NADP+-specific isocitrate dehydrogenase isozymes. These and other results suggest that several major presumed sources of biosynthetic reducing equivalents are non-essential in yeast cells grown under many cultivation conditions. To develop an in vivo system for analysis of metabolic function, mammalian mitochondrial and cytosolic isozymes of NADP+-specific isocitrate dehydrogenase were expressed in yeast using promoters from the cognate yeast genes. The mammalian mitochondrial isozyme was found to be imported efficiently into yeast mitochondria when fused to the Idp1p targeting sequence and to substitute functionally for Idp1p for production of alpha-ketoglutarate. The mammalian cytosolic isozyme was found to partition between cytosolic and organellar compartments and to replace functionally Idp2p for production of alpha-ketoglutarate or for growth on fatty acids in a mutant lacking Zwf1p. The mammalian cytosolic isozyme also functionally substitutes for Idp3p allowing growth on petroselinic acid as a carbon source, suggesting partial localization to peroxisomes and provision of NADPH for beta-oxidation of that fatty acid.

Methyl-branched fatty acids and their biosynthesis in the housefly, Musca domestica L. (Diptera: Muscidae)

Eighteen methyl-branched fatty acids from the housfly, Musca domestica were identified by gas chromatography-mass spectrometry after reduction to the corresponding hydrocarbons. A deuterium was inserted on what was the carboxyl carbon and the straight chain components were removed by molecular sieve. The deuterium allowed the mass spectral determination of the methyl branch position with respect to the carboxyl end of the parent fatty acid methyl-branched fatty acids were characterized as n-2, n-3, n-4, n-5, n-6, n-7, n-8, and n-9 monomethyl fatty acids of 15—19 carbons and a n-3, 7 dimethyl fatty acid of 18 total carbons. These methyl-branched fatty acids have similar branching patterns and are presumed to the precursors to the methyl-branched hydrocarbons, some of which function as an arrestant in the female sex pheromone. With increasing concentrations of methylmalonyl-CoA, its incorporation into methyl-branched fatty acids increased in both day 1 and day 4 males and females using both microsomal and soluble fatty acid synthases (FAS). Methylmalonyl-CoA inhibited both the soluble and microsomal FAS in a competitive manner. The data on the incorporation of methylmalonyl-CoA into methyl-branched fatty acids by day 1 and day 4 males and females indicate that the regulation of methyl-branched hydrocarbon synthesis does not reside at the level of fatty acid synthesis, but must occur during the process of the fatty acyl-CoA elongation or reductive conversion of very long chain fatty acyl-CoAs to hydrocarbons.

Modulation of the hypolipidemic effect of fish oil by inhibition of adipose tissue lipolysis with acipimox, a nicotinic acid analog.

To assess the possible benefits of combined hypolipidemic therapy (acipimox+marine fish oil) on lipid and lipoprotein metabolism, male Wistar rats were fed for 14 days a high sucrose diet (70 cal% sucrose) alone or a high sucrose diet supplemented with acipimox (0.2 g/100 g diet) and/or fish oil (1 ml orally daily; 30 wt% of n-3 PUFA). Feeding a high sucrose diet increased (control: 61 +/- 6 vs HS: 110 +/- 8 nmol.min-1.mg-1, p < 0.001) the activity of acetyl CoA carboxylase in the liver, this was normalized by fish oil but not acipimox alone (HS+FO: 68 +/- 4; HS+ACI: 95 +/- 4; HS+ACI+FO: 71 +/- 2 nmol.min-1.mg-1). Increased triglyceride concentration in serum and muscle tissue (m. soleus and heart) of high sucrose-fed animals was suppressed equally by fish oil, acipimox, and/or both. The cholesterol-lowering effect of fish oil was also present in the liver (p < 0.005). The cholesterol-lowering action of acipimox was accompanied by the accumulation of cholesterol in the liver (p < 0.005), whereas the combination of acipimox+fish oil did not change the liver cholesterol content. After fish oil the LDL binding capacity of liver plasma membranes was increased 1.6-fold (p < 0.001). LDL receptor activity was significantly decreased in HS+ACI group (p < 0.05), but remained unchanged in HS+FO+ACI-fed animals. In summary, (a) the hypotriglyceridemic effect of fish oil in high sucrose-induced HTG is due to its inhibitory effects at the level of fatty acid synthesis; (b) decreased triglyceride production and output from the liver prevent triglyceride accumulation in muscle tissue; (c) the cholesterol-lowering action of acipimox but not fish oil was accompanied by an accumulation of cholesterol in the liver; (d) the latter phenomenon may be due to the opposite effects of both drugs on cholesterol catabolism via hepatic LDL receptors.

A Nuclear Mutation in Nicotiana sylvestris Causing a Thiamine-Reversible Defect in Synthesis of Chloroplast Pigments

We report the recovery of a nuclear recessive mutation in Nicotiana sylvestris (Spegazzini and Comes) producing a conditional disruption in the pathway for synthesis of chlorophyll a and b and carotenoids which is fully reversible by exogenous thiamine (0.3 micromolar). In the absence of supplemental thiamine, chlorophyll levels declined by 50% after 5 days, and fell to undetectable levels by 11 days. Mitochondrial (KCN sensitive) respiration rates remained normal in albino leaves (80% loss of chlorophyll), suggesting that chlorosis results primarily from a deficiency of thiamine in the chloroplasts. After thiamine removal, mutant plants produced at least 10 albino leaves with a substantial capacity for growth (0-15 centimeters; 70-fold increase in area), demonstrating sustained operation of many cellular functions in spite of chloroplast disruption. Activities of the plastid isozymes of phosphoglucomutase and phosphoglucoisomerase in albino leaves indicated that the decline in pigment synthesis does not result from a general loss of metabolic activity in chloroplast. Plastid pyruvate dehydrogenase from mutant and wild-type plants displayed a similar affinity for thiamine pyrophosphate, showing that chlorosis does not result from an alteration in this enzyme. Growth of albino leaves and ultrastructural evidence for thylakoid membranes in the chloroplasts suggest that a certain level of fatty acid synthesis is maintained after the interruption of pigment synthesis. Since thiamine deprivation is expected to block production of acetyl-coenzyme A from pyruvate by pyruvate dehydrogenase, acetyl-coenzyme A supporting fatty acid synthesis in albino leaves may be derived solely from mitochondrial acetate.