Stearoyl-coenzyme A Desaturase Research Articles

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients.

PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase.

Stearoyl‐coenzyme A desaturase (SCD) catalyzes the Δ9‐cis desaturation of saturated fatty acids (SFA) to generate monounsaturated fatty acids (MUFA). This enzyme is highly up‐regulated by platelet‐derived growth factor (PDGF) in human fibroblasts. Accordingly, the analysis of cellular fatty acids by gas chromatography showed that PDGF significantly increased the proportion of MUFA, particularly palmitoleate, in cellular lipids. To further analyze the role of SCD in fibroblasts, we used small hairpin RNA targeting SCD (shSCD), which decreased the MUFA content. SCD down‐regulation blunted the proliferation of fibroblasts in response to PDGF. This was confirmed using a pharmacological inhibitor of SCD. In addition, proliferation was blocked by palmitate and stearate (two SCD substrates) but not by palmitoleate and oleate (two SCD products). In the presence of an equal amount of oleate, palmitate had no effect on cell proliferation. SCD inhibition or down‐regulation did not decrease PDGF receptor activity or signaling. However, by measuring plasma membrane lipid lateral diffusion by fluorescence recovery after photobleaching, we showed that the modulation of the MUFA/SFA ratio by PDGF and SCD inhibitor was related to modifications of membrane fluidity. Altogether, our data suggest that SCD is required for the response of normal fibroblasts to growth factors.

Loss of ULK1 increases RPS6KB1-NCOR1 repression of NR1H/LXR-mediated Scd1 transcription and augments lipotoxicity in hepatic cells

ABSTRACTLipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival. Surprisingly, ULK1/ATG1 (unc-51 like kinase) played a critical role in protecting hepatic cells from SFA-induced lipotoxicity via a novel mechanism that did not involve macroautophagy/autophagy. Specific loss of Ulk1 blocked the induction of Scd1 gene transcription by GW3965, decreased lipid droplet formation, and increased apoptosis in hepatic cells exposed to palmitate. Knockdown of ULK1 increased RPS6KB1 (ribosomal protein S6 kinase, polypeptide 1) signaling that, in turn, induced NCOR1 (nuclear receptor co-repressor 1) nuclear uptake, interaction with NR1H/LXR, and recruitment to the Scd1 promoter. These events abrogated the stimulation of Scd1 gene expression by GW3965, and increased lipotoxicity in hepatic cells. In summary, we have identified a novel autophagy-independent role of ULK1 that regulates NR1H/LXR signaling, Scd1 expression, and intracellular lipid homeostasis in hepatic cells exposed to a lipotoxic environment.

85 REGULATION OF STEAROYL-CoENZYME A DESATURASE BY FATTY ACIDS IS ESSENTIAL TO PORCINE EARLY EMBRYO DEVELOPMENT

Various fatty acids are found in large amounts in follicular fluid and the uterus. These fatty acids are known to regulate lipid metabolism in a mammal’s embryo. Lipid metabolism provides a source of energy, and its importance during embryogenesis is being increasingly recognised. Especially, the pig has larger amounts of intercellular lipid bilayers in the embryo than do other species, which indicates the porcine embryo is more dependent on fatty acid on their metabolic pathway. This study investigated the transcriptome analysis data of in vivo embryos and the effect of oleic acid (C18:1n-9) and stearic acid (C18:0) on in vitro-produced porcine embryos. In transcriptome analysis of in vivo embryos, we found several genes were increasing before and after maternal zygotic transition stage, and interactions were mapped and given a significance score. Among these genes, stearoyl-coenzyme A desaturase (SCD) gene was significantly increased during 8-cell to blastocyst stage. Stearoyl-coenzyme A desaturase is responsible for converting saturated fatty acid (stearic acid) to monounsaturated fatty acid (oleic acid). Furthermore, we treated with oleic acid (50, 100, 250, and 500 μM) and stearic acid (50, 75, and 100 μM) on 2 day and 4 day after parthenogenetic embryos. Both oleic acid and stearic acid concentration over 100 μM had a negative effect on blastocyst formation rate and cell numbers because of exogenous fatty acid toxicity. In addition, there was no significant difference among all stearic acid treated groups and total cell number of oleic acid treated blastocyst. However, the 2-day oleic acid treated group (45.92 ± 4.01, n = 8, 2 day, 100 μM) had a significant increase of blastocyst formation rate (P < 0.05) compared with the control group (34.88 ± 2.93, n = 8). These data could support that porcine embryos can use exogenous oleic acid as a metabolic energy source. The data also demonstrate the important role of SCD in porcine early embryo development. To confirm the transcriptome analysis, we are investigating mRNA level of SCD on in vitro-produced embryos at 1-cell to morula and blastocyst stage on the control group, oleic acid treated group, fetal bovine serum treated group, and nontreated group. Furthermore, we are investigating SCD inhibition assay by A939572 (SCD inhibitor) on parthenogenetic embryos in a fetal bovine serum treated group and nontreated group for identifying blastocyst formation rate and total cell numbers. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2055199) and Next BioGreen 21 program (PJ0113002016), Rural Development Administration, Republic of Korea.

Exploring the Lean Phenotype of Glutathione-Depleted Mice: Thiol, Amino Acid and Fatty Acid Profiles.

BackgroundAlthough reduced glutathione (rGSH) is decreased in obese mice and humans, block of GSH synthesis by buthionine sulfoximine (BSO) results in a lean, insulin-sensitive phenotype. Data is lacking about the effect of BSO on GSH precursors, cysteine and glutamate. Plasma total cysteine (tCys) is positively associated with stearoyl-coenzyme A desaturase (SCD) activity and adiposity in humans and animal models.ObjectiveTo explore the phenotype, amino acid and fatty acid profiles in BSO-treated mice.DesignMale C3H/HeH mice aged 11 weeks were fed a high-fat diet with or without BSO in drinking water (30 mmol/L) for 8 weeks. Amino acid and fatty acid changes were assessed, as well as food consumption, energy expenditure, locomotor activity, body composition and liver vacuolation (steatosis).ResultsDespite higher food intake, BSO decreased particularly fat mass but also lean mass (both P<0.001), and prevented fatty liver vacuolation. Physical activity increased during the dark phase. BSO decreased plasma free fatty acids and enhanced insulin sensitivity. BSO did not alter liver rGSH, but decreased plasma total GSH (tGSH) and rGSH (by ~70%), and liver tGSH (by 82%). Glutamate accumulated in plasma and liver. Urine excretion of cysteine and its precursors was increased by BSO. tCys, rCys and cystine decreased in plasma (by 23–45%, P<0.001 for all), but were maintained in liver, at the expense of decreased taurine. Free and total plasma concentrations of the SCD products, oleic and palmitoleic acids were decreased (by 27–38%, P <0.001 for all).ConclusionCounterintuitively, block of GSH synthesis decreases circulating tCys, raising the question of whether the BSO-induced obesity-resistance is linked to cysteine depletion. Cysteine-supplementation of BSO-treated mice is warranted to dissect the effects of cysteine and GSH depletion on energy metabolism.

Variations in genes involved in fat metabolism and their association with ultrasonic and carcass traits in Japanese Black steers.

Polymorphisms in genes involved in lipid metabolism have been reported to be associated with fatty acid composition of adipose tissue. However, the relationship of these polymorphisms with premortem ultrasonic traits is unknown. The objective of this study, therefore, was to assess the association between polymorphisms in fatty acid synthase, stearoyl-coenzyme A desaturase (SCD), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol acyltransferase 1, and nuclear receptor subfamily 1, group H, number 3 genes with ultrasonic and carcass traits in Japanese Black steers (n = 300) under progeny testing at the Livestock Improvement Association of Miyazaki. To have a comprehensive analysis of the association between the aforementioned genetic polymorphisms and ultrasonic traits, longitudinal measurements of ultrasonic traits were taken. Furthermore, the association of these genetic polymorphisms and carcass traits was evaluated. The polymorphisms in the SCD gene and SREBP1 were associated (P < 0.05) with some ultrasonic traits at multiple stages. To add to that, the polymorphisms were associated (P < 0.05) with some carcass traits. These findings suggest that the polymorphisms in SCD and SREBP1 are functional mutations or could be related to mutations that can aid in selection to improve some ultrasonic and carcass traits.

Effect of polymorphisms in the ABCG2, LEPR and SCD1 genes on milk production traits in Holstein cows

This study was performed to investigate the association between polymorphisms in the ABCG2 (ATP-binding cassette sub-family G member 2), LEPR (leptin receptor) and SCD1 (stearoyl-coenzyme A desaturase 1) genes and milk production traits in Holstein dairy cows in Iran. The analysis was conducted on 816 lactations from 408 Iranian Holstein cows. Genotyping was carried out using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique. The results of the association study revealed that cows with genotype AC of the ABCG2-Y581S single nucleotide polymorphism (SNP) had lower breeding value for milk yield compared with the AA genotype, but showed significantly higher fat and protein percentages. Cows that were homozygous for allele T at the LEPR-T945M locus had higher breeding value for fat yield than those that were homozygous for the C allele. Regarding the SCD1-A293V SNP, cows with genotype AV produced a higher 305-day milk yield in comparison with cows with the VV genotype. Furthermore, cows that were homozygous for allele V showed a significantly higher protein percentage compared with AA and AV genotypes. The results of this study suggest that these SNPs have the potential to be used in programmes based on genomic selection in Iranian dairy herds. ______________________________________________________________________________________ Keywords : Genetic polymorphism, Iranian Holstein, milk fat, milk protein, SNP

A novel selection signature in stearoyl-coenzyme A desaturase (SCD) gene for enhanced milk fat content in Bubalus bubalis

Modern molecular interventions are dynamic gears for breeding animals with superior genetic make-up. These scientific efforts lead us toward sustainable dairy herds with improved milk production in terms of yield and quality. Many of candidate genes have been dissected at molecular level, and suitable genetic markers have been identified in cattle, but this work has not been validated in buffaloes so far. Stearoyl-coenzyme A desaturase (SCD) has been a potential candidate gene for fat content of milk. Genomic analysis of SCD revealed a total of six variations that were identified through DNA sequencing of animals with lower and higher butter fat %age. After statistical analysis, genotype AB of p.K158I could be associated (P value <0.0001) with higher milk fat %age (10.5 ± 0.5464). This SNP was validated on larger data set by cleaved amplified polymorphic sequences (CAPS) by using DdeI. To scrutinize the functional consequences of p.K158I, 3D protein structure of SCD was predicted by homology modeling and this variation was found located in the vicinity of functional domain and a part of transmembrane helix of this membrane integrated protein. This is a first report toward genetic screening of SCD gene at molecular level in buffalo. This report illustrates the implication of SCD gene and in particular p.K158I variation, in imparting its effect on milk fat %age, which can be targeted in selection of superior dairy buffaloes.

Liver X receptor α promotes the synthesis of monounsaturated fatty acids in goat mammary epithelial cells via the control of stearoyl-coenzyme A desaturase 1 in an SREBP-1-dependent manner

Stearoyl-coenzyme A desaturase 1 (SCD1) is a pivotal enzyme in the biosynthesis of monounsaturated fatty acids (MUFA). It is tightly regulated by transcription factors that control lipogenesis. In nonruminants, liver X receptor α (LXRα) is a nuclear receptor and transcription factor that acts as a key sensor of cholesterol and lipid homeostasis. However, the mechanism whereby LXRα regulates the expression and transcriptional activity of SCD1 in ruminant mammary cells remains unknown. In this study with goat mammary epithelial cells (GMEC), the LXRα agonist T 4506585 (T09) markedly enhanced the mRNA expression of SCD1 and sterol regulatory element binding factor 1 (SREBF1). The concentrations of C16:1 and C18:1 and their desaturation indices also were increased by LXRα activation. However, knockdown of LXRα did not alter the mRNA expression of SCD1. Although SCD1 was repressed by SREBF1 knockdown, T09 significantly increased SCD1 expression. Further analysis revealed that the SCD1 promoter activity was activated by LXRα overexpression. The goat SCD1 promoter contains 2 LXR response elements (LXRE), 1 sterol response element (SRE), and 1 nuclear factor Y (NF-Y) binding site. Site-directed mutagenesis of LXRE1, LXRE2, or SRE alone did not eliminate the upregulation of SCD1 when LXRα was overexpressed. In contrast, when NF-Y alone or in combination with SRE was mutated simultaneously, the basal transcriptional activity of the SCD1 promoter was markedly decreased and did not respond to LXRα overexpression. Furthermore, when SREBF1 was knocked down, overexpression of LXRα did not affect the promoter activity of SCD1. Together, these data suggest that LXRα regulates the expression of SCD1 through increasing SREBP-1 abundance to promote interaction with SRE and NF-Y binding sites. The present study provides evidence that LXRα is involved in the synthesis of MUFA in the goat mammary gland through an indirect mechanism.

Characterization of the liver X receptor-dependent regulatory mechanism of goat stearoyl-coenzyme A desaturase 1 gene by linoleic acid

Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in the biosynthesis of palmitoleic and oleic acid. Although the transcriptional regulatory mechanism of SCD1 via polyunsaturated fatty acids (PUFA) has been extensively explored in nonruminants, the existence of such mechanism in ruminant mammary gland remains unknown. In this study, we used goat genomic DNA to clone and sequence a 1,713-bp fragment of the SCD1 5′ flanking region. Deletion assays revealed a core region of the promoter located between −415 and −109 bp upstream of the transcription start site, and contained the highly conserved PUFA response region. An intact PUFA response region was required for the basal transcriptional activity of SCD1. Linoleic acid reduced endogenous expression of SCD1 and sterol regulatory element binding factor-1 (SREBF1) in goat mammary epithelial cells. Further analysis indicated that both the sterol response element (SRE) and the nuclear factor Y (NF-Y) binding site in the SCD1 promoter were responsible for the inhibition effect by linoleic acid, whereas the effect was abrogated once NF-Y was deleted. In addition, SRE and NF-Y were partly responsible for the transcriptional activation induced via the liver X receptor agonist T 4506585 (Sigma-Aldrich, St. Louis, MO). When goat mammary epithelial cells were cultured with linoleic acid, addition of T 4506585 markedly increased SCD1 transcription in controls, but had no effect on cells with a deleted SRE promoter. These results demonstrated that linoleic acid can regulate SCD1 expression at the transcriptional level through SRE and NF-Y in a liver X receptor-dependent fashion in the goat mammary gland.

Polymorphism in the SCD gene is associated with meat quality and fatty acid composition in Iranian fat- and thin-tailed sheep breeds

The enzyme stearoyl-coenzyme A-desaturase (SCD) has been proposed as a key regulator for fat content and fatty acid composition of meat. In this study, a DNA sequence and single-strand confirmation polymorphism analysis were performed in an attempt to investigate the relationship between variation within the SCD gene and fatty acid profiles, physicochemical composition, and the quality characteristics of longissimus dorsi (LD) muscle in two traditional fat- (Chall) and thin- (Zel) tailed Iranian sheep breeds. Only one previously reported SNP (g.379A>T) located in the 5′ untranslated region of the SCD gene was observed. Two previously reported allelic variants, SCD-1 and SCD-2, constituted two previously reported genotypes, “A” and “B”. Based on t-test, no allelic and genotypic frequency differences were observed between Chall and Zel breeds. Lambs with genotype “B” significantly had lower total saturated fatty acid (SFA) level (p<0.05) and more linoleic (p<0.02), arachidonic (p<0.002), and eicosapentaenoic (EPA) (p<0.001) acids and total poly-unsaturated fatty acid (PUFA) (p=0.002) contents and PUFA: SFA ratio (p<0.004) than those with genotype “A”. Meat color of the genotype “B” lambs was lower for a* (p<0.05) and higher for L* (p<0.08) compared to the genotype “A” ones. There were some interactions between breed and SCD gene in terms of palmitic acid (p<0.04), cooking loss (p<0.05), and protein content (p<0.03) of LD muscle. SCD locus explained 17.3%, 15.3%, 13%, and 12% of the phenotypic variation in terms of EPA and arachidonic acid, and PUFA contents and PUFA: SFA ratio, respectively. Interestingly, the results of the correlation analyses showed the significant negative correlations between healthy fatty acid indices (PUFA and PUFA: SFA) and meat color measures of a* and b* (r=−0.26 to r=−0.40, p<0.05) and the significant positive correlations between n–6: n–3 PUFA, one of the main harmful fatty acid indices, and a* (r=0.41, p<0.01) and b* (r=0.27, p<0.05) values which are coordinated with the effect of SCD genotypes on fatty acid composition and color of meat. So, both fatty acid composition and meat color traits should be considered in marker-assisted selection based on SCD gene. Overall, it seems that the genotype “B” of SCD gene is a more desirable genotype when selecting lambs in terms of both fatty acid composition and color of meat, because selecting this genotype would result in higher proportion of healthy fatty acids, lower proportion of harmful fatty acids, and better meat color.

Thyroid hormone responsive (THRSP) promotes the synthesis of medium-chain fatty acids in goat mammary epithelial cells

In nonruminants, thyroid hormone responsive (THRSP) is a crucial protein for cellular de novo lipogenesis. However, the role of THRSP in regulating the synthesis of milk fatty acid composition in goat mammary gland remains unknown. In the present study, we compared gene expression of THRSP among different goat tissues. Results revealed that THRSP had the highest expression in subcutaneous fat, and expression was higher during lactation compared with the dry period. Overexpression of THRSP upregulated the expression of fatty acid synthase (FASN), stearoyl-coenzyme A desaturase 1 (SCD1), diacylglycerol acyltransferase 2 (DGAT2), and glycerol-3-phosphate acyltransferase (GPAM) in goat mammary epithelial cells. In contrast, overexpression of THRSP led to downregulation of thrombospondin receptor (CD36) and had no effect on the expression of acetyl-coenzyme A carboxylase α (ACACA) and sterol regulatory element binding transcription factor1 (SREBF1). In addition, overexpressing THRSP in vitro resulted in a significant increase in triacylglycerol (TAG) concentration and the concentrations of C12:0 and C14:0. Taken together, these results highlight an important role of THRSP in regulating lipogenesis in goat mammary epithelial cells.

Patatin-like phospholipase domain-containing protein 3 is involved in hepatic fatty acid and triglyceride metabolism through X-box binding protein 1 and modulation of endoplasmic reticulum stress in mice.

Non-alcoholic steatohepatitis (NASH) is the major cause of chronic liver disease worldwide. Endoplasmic reticulum (ER) stress is considered to be an important pathological characteristic in NASH. A sequence variation (I148M) in the patatin-like phospholipase domain-containing protein 3/adiponutrin (PNPLA3) gene is known to be associated with the development of NASH. However, PNPLA3 deficiency has been considered to not be associated with fatty liver disease. To clarify, therefore, the role of PNPLA3 in liver, we established PNPLA3 knockout (KO) mice and investigated the phenotypes and involved factors under ER stress. ER stress was induced by i.p. injection with tunicamycin or with saline at 0 and 24h in KO and C57BL/6 (wild-type [WT]) mice. At 48h after the starting of treatment, blood and liver samples were studied. Hepatic steatosis and triglyceride content were remarkably increased in WT mice than in KO mice under ER stress. The hepatic palmitate/oleate ratio was significantly higher originally in KO mice than in WT mice. Moreover, the expression of stearoyl-coenzyme A desaturase-1 (SCD1) in KO mice under ER stress was decreased further than that in WT mice. Expression of ER stress markers X-box binding protein 1 (XBP1) and ERdj4 was increased in WT mice but not in KO mice under ER stress. We first demonstrated the hepatic phenotype of PNPLA3 deficiency under ER stress. Our observations would indicate that PNPLA3 has an important role in hepatic fatty acid metabolism and triglyceride accumulation through XBP1 under ER stress.

Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes.

Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. Previously we found that cocoa tea demonstrated a beneficial effect against high-fat diet induced obesity, hepatic steatosis, and hyperlipidemia in mice. The present study aimed to investigate the anti-adipogenic effect of cocoa tea in vitro using preadipocytes 3T3-L1. Adipogenic differentiation was confirmed by Oil Red O stain, qPCR and Western blot. Our results demonstrated that cocoa tea significantly inhibited triglyceride accumulation in mature adipocytes in a dose-dependent manner. Cocoa tea was shown to suppress the expressions of key adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPAR γ) and CCAAT/enhancer binding protein (C/EBP α). The tea extract was subsequently found to reduce the expressions of adipocyte-specific genes such as sterol regulatory element binding transcription factor 1c (SREBP-1c), fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC), fatty acid translocase (FAT) and stearoylcoenzyme A desaturase-1 (SCD-1). In addition, JNK, ERK and p38 phosphorylation were inhibited during cocoa tea inhibition of 3T3-L1 adipogenic differentiation. Taken together, this is the first study that demonstrates cocoa tea has the capacity to suppress adipogenesis in pre-adipocyte 3T3-L1 similar to traditional green tea

가미한다열소탕(加味寒多熱少湯)이 고지방식이 비만생쥐의 체지방감소에 미치는 영향

Objectives In this study, it was investigated whether Gami-Handayeolso-Tang (HDYST) medication has anti-obesity effects in high fat diet (HFD)-fed obese mice. Methods The experimental animals were divided into five groups-normal diet-fed (ND), high fat diet-fed control (HFD), HFD+HDYST 150, HFD+HDYST 300, and HFD+orlistat as a positive drug. The obese markers such as body weight, diet efficiency ratio, serum levels of total cholesterol, triglyceride, lipid contents, leptin, adiponectin, and GOT/GPT were measured. Also, white adipose tissue, liver weight, abdominal fat mass, hepatic lipid contents, and mRNA expression of obese-associating genes were examined in obese mice. Results In high fat diet-fed mice, HDYST administration significantly decreased body weight, diet efficiency ratio, serum levels of total cholesterol, triglyceride, LDL-cholesterol, as well as leptin and GOT/GPT, compared to the HFD group in a dose-dependent manner. HDYST increased significantly the serum levels of HDL-cholesterol and adiponectin. It also reduced the accumulation of lipids, such as total lipid and triglycerides, in organs such as liver and abdominal adipose tissue. Moreover, HDYST administration significantly decreased the expression levels of fatty acid synthetic genes, such as sterol regulatory element-binding protein-1c (SREBP-1c), FAS and Stearoyl-Coenzyme A desaturase 1 (SCD-1), in the liver tissues, while it increased the messenger RAN (mRNA) levels of fatty acid catalytic genes, such as Peroxisome proliferator activated receptor alpha (PPAR-), acyl-COA oxidase (ACO), and Carnitine palmitoyltransferase-1a (CPT-1a). Conclusions Based on the results above, HDYST reveals anti-obesity effects declining body fat accumulation through the regulation of fatty acid metabolism and leptin/adiponectin serum levels. It therefore suggests that HDYST can be clinically useful for the treatment of obesity.

Novel single nucleotide polymorphisms in the 5' regulatory region of the duck SCD1 gene and their associations with serum biochemical levels and fatty acid composition.

Stearoyl-coenzyme A desaturase 1 (SCD1) is the key limiting enzyme in the synthesis of monounsaturated fatty acids, and plays a crucial role in the regulation of oleic acid. In this study, 165 ten-week-old Cherry Valley ducks were used to investigate single nucleotide polymorphisms (SNPs) in the 5' regulatory region of the SCD1 gene, and their associations with duck serum biochemical levels and fatty acid composition. Two novel SNPs, g.936516 C > G and g.936551 T > C, were found by polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing methods, exhibiting six genotypes (AA, BB, CC, AB, AC, and BC). The frequency of the dominant genotype BB and allele B was 0.321 and 0.403, respectively. The polymorphism information content value was 0.617, indicating high polymorphism. The chi-square test indicated that the genotype distribution deviated markedly from Hardy-Weinberg equilibrium (P < 0.01). The linkage of the two mutant sites in the duck SCD1 gene had significant effects on the serum albumin, total protein, globulin, triglyceride, total cholesterol, and cholinesterase levels, as well as on 16 kinds of fatty acids except for C14:1 and C20:0 (P < 0.05). These results indicated that the C allele might have a positive effect on polyunsaturated fatty acids with potential health benefits. Therefore, the SCD1-gene-specific SNPs in the 5' regulatory region may be a useful marker for serum lipid, serum protein, and fatty acid composition in future marker-assisted selection for duck breeding.

MicroRNA-192* impairs adipocyte triglyceride storage

We investigated the expression of miR-192* (miR-192-3p) in the visceral adipose tissue (VAT) of obese subjects and its function in cultured human adipocytes. This miRNA is a 3′ arm derived from the same pre-miRNA as miR-192 (miR-192-5p) implicated in type 2 diabetes, liver disease and cancers, and is predicted to target key genes in lipid metabolism. In morbidly obese subjects undergoing bariatric surgery preceded by a very low calorie diet, miR-192* in VAT correlated negatively (r=−0.387; p=0.046) with serum triglyceride (TG) and positively with high-density lipoprotein (HDL) concentration (r=0.396; p=0.041). In a less obese patient cohort, the miRNA correlated negatively with the body mass index (r=−0.537; p=0.026). To characterize the function of miR-192*, we overexpressed it in cultured adipocytes and analyzed the expression of adipogenic differentiation markers as well as cellular TG content. Reduced TG and expression of the adipocyte marker proteins aP2 (adipocyte protein 2) and perilipin 1 were observed. The function of miR-192* was further investigated by transcriptomic profiling of adipocytes expressing this miRNA, revealing impacts on key lipogenic genes. A number of the mRNA alterations were validated by qPCR. Western analysis confirmed a marked reduction of the lipogenic enzyme SCD (stearoyl coenzyme A desaturase-1), the fatty aldehyde dehydrogenase ALDH3A2 (aldehyde dehydrogenase 3 family member A2) and the high-density lipoprotein receptor SCARB1 (scavenger receptor B, type I). SCD and ALDH3A2 were demonstrated to be direct targets of miR-192*. To conclude, the present data identify miR-192* as a novel controller of adipocyte differentiation and lipid homeostasis.

Dietary conjugated linoleic acids increase intramuscular fat deposition and decrease subcutaneous fat deposition in Yellow Breed × Simmental cattle.

This study was conducted to estimate the effect of dietary conjugated linoleic acids (CLA) on intramuscular and subcutaneous fat deposition in Yellow Breed × Simmental cattle. The experiment was conducted for 60 days. The results showed that the average backfat thickness, (testicles + kidney + pelvic) fat percentage and subcutaneous fat percentage in dietary CLA were significantly lower than in the control group, while intramuscular the fat percentage was significantly higher. Compared to the control group, the Longissimus muscle enzyme activities of lipoprotein lipase (LPL), fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase (ACC) in dietary CLA and the subcutaneous fat enzyme activities of LPL, hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) were significantly increased. Similarly, compared to the control group, the Longissimus muscle sterol regulatory element binding protein 1 (SREBP-1), FAS, stearoyl-coenzyme A desaturase (SCD), ACC, peroxisome proliferator-activated receptor γ (PPARγ), heart fatty-acid binding protein (H-FABP) and LPL gene expression in dietary CLA were significant increased, as were the subcutaneous fat of PPARγ, H-FABP, LPL, CPT-1 and HSL in dietary CLA. These results indicated that dietary CLA increases IMF deposition mainly by the up-regulation of lipogenic gene expression, while decreasing subcutaneous fat deposition mainly by the up-regulation of lipolytic gene expression.

Relationship of Circulating Fatty Acid Profile to Metabolic Disorders Associated with Insulin Resistance

Relationship of Circulating Fatty Acid Profile to Metabolic Disorders Associated with Insulin Resistance

Anti-adipogenic activity of a new cyclic diarylheptanoid isolated from Alnus japonica on 3T3-L1 cells via modulation of PPARγ, C/EBPα and SREBP1c signaling

Total methanolic extract of Alnus japonica fruits exhibited significant anti-adipogenic activities in 3T3-L1 cells. A new cyclic diarylheptanoid (1) along with ten known compounds (2-11) were isolated by activity-guided fractionation. Compound 1, determined to be 4-hydroxy-alnus-3,5-dione, showed the most potent anti-adipogenic effect. Compound 1 significantly down-regulated expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and sterol regulatory element binding protein 1 (SREBP1c) in 3T3-L1 cells, as determined by quantitative real-time PCR and Western blot analysis. Furthermore, compound 1 suppressed mRNA expression of C/EBPβ and C/EBPδ during the early stage of adipogenesis as well as stearoyl coenzyme A desaturase 1 (SCD-1) and fatty acid synthase (FAS), target genes of SREBP1c. Upon investigating the mechanism of natural products, we propose that cyclic diarylheptanoid (1), the most potent constituent of A. japonica, can be a potent therapeutic agent against obesity through anti-adipogenesis via down-regulation of PPARγ, C/EBPα, and SREBP1c signaling.