Expression Of LPL Research Articles

5-Hydroxyferulic acid methyl ester isolated from wasabi leaves inhibits 3T3-L1 adipocyte differentiation.

To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα. Furthermore, 1 downregulated the expression of adipogenesis-related genes, GLUT4, LPL, SREBP-1c, ACC, and FAS. Protein expression analysis revealed that 1 suppressed PPARγ protein expression. Moreover, to investigate the relationship between the structure and activity of inhibiting the adipocyte differentiation, we synthesized 12 kinds of phenylpropanoid analog. Comparison of the activity among 1 and its analogs suggested that the compound containing the substructure that possess a common functional group at the ortho position such as a catechol group exhibits the activity of inhibiting the adipocyte differentiation. Taken together, our findings suggest that 1 from wasabi leaves inhibits adipocyte differentiation via the downregulation of PPARγ.

Panaxadiol saponins treatment caused the subtle variations in the global transcriptional state of Asiatic corn borer, Ostrinia furnacalis

BackgroundThe lepidopteran Asiatic corn borer (ACB), Ostriniafurnacalis (Guenee), has caused huge economic losses throughout the Asian-Western Pacific region. Usually, chemical pesticides are used for the control, but excessive use of pesticides has caused great harm. Therefore, the inartificial ecotypic pesticides to ACB are extremely essential. In our previous study, we found that panaxadiol saponins (PDS) can effectively reduce the harm of ACB by causing antifeedant activity. Therefore, it is necessary to reveal the biological molecular changes in ACB and the functionary mechanism of PDS. MethodsWe analyzed the global transcription of ACB with different PDS concentration treatment (5 mg/mL, 10 mg/mL, and 25 mg/mL) by high-throughput sequencing and de novo transcriptome assembly method. ResultsPDS treatment could cause the changes of many gene expressions which regulate its signal pathways. The genes in peroxisome proliferator–activated receptor (PPAR) signaling pathway were significantly downregulated, and then, the downstream fatty acid degradation pathway had also been greatly affected. ConclusionThrough this experiment, we hypothesized that the occurrence of antifeedant action of ACB is because the PDS brought about the downregulation of FATP and FABP, the key regulators in the PPAR, and the downregulation of FATP and FABP exerts further effects on the expression of SCD-1, ACBP, LPL, SCP-X, and ACO, which leads to the disorder of PPAR signaling pathway and the fatty acid degradation pathway. Not only that, PDS treatment leads to enzyme activity decrease by inhibiting the expression of genes associated with catalytic activity, such as cytochrome P450 and other similar genes.

Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells

Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.01–25 μM) of DiNP (Di-iso-nonyl-phthalate), DiDP (Di-iso-decyl-phthalate), DEGDB (Diethylene glycol dibenzoate), or TMCP (Tri-m-cresyl phosphate). Rosiglitazone, a well-known pro-adipogenic peroxisome proliferator activated receptor gamma (PPARγ) agonist, and the plasticizer BPA were included as reference compounds. All concentrations of plasticizers were able to enhance lipid accumulation, with TMCP being the most effective one. Accordingly, when comparing in silico the ligand binding efficiencies to the nuclear receptors PPARγ and retinoid-X-receptor-alpha (RXRα), TMPC displayed the highest affinity to both receptors. Differently from BPA, the four plasticizers were most effective in enhancing lipid accumulation when added in the mid-late phase of differentiation, thus suggesting the involvement of different intracellular signalling pathways. In line with this, TMCP, DiDP, DiNP and DEGDB were able to activate PPARγ in transient transfection assays, while previous studies demonstrated that BPA acts mainly through other nuclear receptors. qRT-PCR studies showed that all plasticizers were able to increase the expression of CCAAT/enhancer binding protein β (Cebpβ) in the early steps of adipogenesis, and the adipogenesis master gene Pparγ2 in the middle phase, with very similar efficacy to that of Rosiglitazone. In addition, TMCP was able to modulate the expression of both Fatty Acid Binding Protein 4/Adipocyte Protein 2 (Fabp4/Ap2) and Lipoprotein Lipase (Lpl) transcripts in the late phase of adipogenesis. DEGDB increased the expression of Lpl only, while the phthalate DiDP did not change the expression of either late-phase marker genes Fabp4 and Lpl. Taken together, our results suggest that exposure to low, environmentally relevant doses of the plasticizers DiNP, DiDP, DEGDB and TMCP increase lipid accumulation in 3T3-L1 adipocytes, an effect likely mediated through activation of PPARγ and interference at different levels with the transcriptional cascade driving adipogenesis.

Cholecystokinin is involved in triglyceride fatty acid uptake by rat adipose tissue.

The incorporation of plasma triglyceride (TG) fatty acids to white adipose tissue (WAT) depends on lipoprotein lipase (LPL), which is regulated by angiopoietin-like protein-4 (ANGPTL-4), an unfolding molecular chaperone that converts active LPL dimers into inactive monomers. The production of ANGPTL-4 is promoted by fasting and repressed by feeding. We hypothesized that the postprandial hormone cholecystokinin (CCK) facilitates the storage of dietary TG fatty acids in WAT by regulating the activity of the LPL/ANGPTL-4 axis and that it does so by acting directly on CCK receptors in adipocytes. We report that administration of CCK-8 (a bioactive fragment of CCK) to rats: (i) reduces plasma ANGTPL-4 levels; (ii) represses Angptl-4 expression in WAT and (iii) simultaneously enhances LPL activity in this tissue without inducing Lpl expression. In vivo CCK-8 effects are specifically antagonized by the CCK-2 receptor (CCK-2R) antagonist, L-365,260. Moreover, CCK-8 downregulates Angptl-4 expression in wild-type pre-adipocytes, an effect that is not observed in engineered pre-adipocytes lacking CCK-2R. These effects have functional consequences as CCK-8 was found to promote the uptake of dietary fatty acids by WAT, as demonstrated by means of proton nuclear magnetic resonance (1H-NMR). The efficacy of acute CCK-8 administration was not reduced after chronic CCK-8 treatment. Moreover, the effects of CCK-8 on WAT were not associated to the increase of circulating insulin. Our results show that cholecystokinin promotes lipid storage in WAT by acting on adipocyte CCK-2R, suggesting a pivotal role for CCK in TG homeostasis.

Bergenin, Acting as an Agonist of PPARγ, Ameliorates Experimental Colitis in Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-κB-Mediated Macrophage Activation.

Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao), has anti-inflammatory, antitussive and wound healing activities. The aim of the present study was to identify the effect of bergenin on experimental colitis, and explored the related mechanisms. Our results showed that oral administration of bergenin remarkably alleviated disease symptoms of mice with dextran sulfate sodium (DSS)-induced colitis, evidenced by reduced DAI scores, shortening of colon length, MPO activity and pathologic abnormalities in colons. Bergenin obviously inhibited the mRNA and protein expressions of IL-6 and TNF-α in colon tissues, but not that of mucosal barrier-associated proteins occludin, E-cadherin and MUC-2. In vitro, bergenin significantly inhibited the expressions of IL-6 and TNF-α as well as nuclear translocation and DNA binding activity of NF-κB-p65 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and RAW264.7 cells, which was almost reversed by addition of PPARγ antagonist GW9662 and siPPARγ. Subsequently, bergenin was identified as a PPARγ agonist. It could enter into macrophages, bind with PPARγ, promote nuclear translocation and transcriptional activity of PPARγ, and increase mRNA expressions of CD36, LPL and ap2. In addition, bergenin significantly up-regulated expression of SIRT1, inhibited acetylation of NF-κB-p65 and increased association NF-κB-p65 and IκBα. Finally, the correlation between activation of PPARγ and attenuation of colitis, inhibition of IL-6 and TNF-α expressions, NF-κB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could ameliorate colitis in mice through inhibiting the activation of macrophages via regulating PPARγ/SIRT1/NF-κB-p65 pathway. The findings can provide evidence for the further development of bergenin as an anti-UC drug, and offer a paradigm for the recognization of anti-UC mechanisms of compound with similar structure occurring in traditional Chinese medicines.

Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD.

People are frequently and unintentionally exposed to many chemical compounds, such as environmental pollutants and endocrine-disrupting chemicals (EDCs), in food and from the atmosphere. In particular, endocrine-disrupting TBBPA and dioxins are found in human breast milk and in the body. Conventional studies evaluate toxicity by administering a single substance to cells or animals, but evaluation of the toxicity of mixtures of these ingested compounds is essential for “true” toxicological assessment. We evaluated toxic effects in vitro using human mesenchymal stem cells (hMSCs). TBBPA increased the number of lipid droplets, and upregulated the expression of adipocyte-related mRNA, aP2 and LPL, through a PPARγ-dependent mechanism. TCDD suppressed lipid droplets and adipocyte-related mRNA levels. Adipocyte differentiation was stimulated by TBBPA and inhibited by TCDD in a dose-dependent manner. TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances.

SOST Gene Inhibits Osteogenesis from Adipose-Derived Mesenchymal Stem Cells by Inducing Th17 Cell Differentiation

Background/Aims: Postmenopausal osteoporosis is considered to be an autoimmune and inflammatory process, and IL-17 plays important roles in the loss of bone mass. Sclerostin (SOST) acts as a negative regulator of bone formation by inhibiting the Wnt signaling pathway. It also is a mediator of the crosstalk between the skeletal and immune systems. However, few studies have examined the role of SOST gene in the differentiation of T helper 17 (Th17) cells. Methods: Adipose-derived stem cells (ADSCs) were isolated and transfected with pcDNA3-SOST or shSOST, and then co-cultured with CD4+ T cells isolated from peripheral blood mononuclear cells. The differentiation, adipogenesis, and osteogenesis of Th17 and regulatory T (Treg) cells were examined by western blot, intracellular and intranuclear staining, ELISA, and real-time quantitative PCR in this co-culture model. Results: The SOST gene promoted the secretion of IL-6 and TGF-β in ADSCs. After co-culture of ADSCs with CD4+ T cells, the SOST gene increased the number of CD4+IL-17+ cells and the levels of IL-17 and RORγ. However, the number of CD4+CD25+Foxp3+ cells was decreased, which was accompanied with a reduction of IL-10 and Foxp3 expression. In the meantime, the SOST gene inhibited the expression of COL1, OCN, and OPN, reduced the activity of alkaline phosphatase, and increased the expression of LPL and PPARγ. Furthermore, IL-17 promoted SOST gene-induced adipogenesis and increased the inhibition of osteogenesis. Conclusions: SOST promoted the differentiation of Th17 cells and reduced the differentiation of Treg cells, which exacerbated the SOST gene-induced inhibition of osteogenesis from ADSCs.

Over-expression of PPAR-γ2 gene enhances the adipogenic differentiation of hemangioma-derived mesenchymal stem cells in vitro and in vivo.

BackgroundMost of infantile hemangiomas involute into fibrofatty tissue in childhood, which indicates adipogenesis during this period. Mesenchymal stem cells (MSCs) contribute to the adipogenesis in IH. In this study, we investigated the effects of overexpression of PPAR-γ2 gene on the adipogenic differentiation of Hemangioma-derived MSCs (Hem-MSCs), and discussed the possibility of targeted therapy via PPAR-γ pathway.MethodsMSCs were isolated from proliferating hemangioma by their selective adhesion to plastic culture dishes. Recombinant lentivirus with PPAR-γ2 gene were prepared, and used to transfect Hem-MSCs. Transfected cells were cultured in adipogenic medium to observe the differentiation in vitro. And the cells were mixed with Matrigel, then subcutaneously injected into the back of nude mice to observe the differentiation in vivo.ResultsIn the in vitro tests, Hem-MSCs with overexpression of PPAR-γ2 gene showed enhanced adipogenic differentiation with increased expression of adipogenic-related genes, including PPAR-γ2, ADD1, LPL, and CEBPA genes. In the in vivo tests, Hem-MSCs/Matrigel plugs with overexpression of PPAR-γ2 gene also showed accelerated adipogenesis and time-phased changes of above genes.ConclusionsOverexpression of PPAR-γ2 gene enhances and accelerates the adipogenic differentiation of Hem-MSCs in vitro and in vivo. The results may provide the preliminary evidences for the targeted therapy of IH via PPAR-γ signal pathway.

Replacement of oat grass with highland barley straw: effects on lipid profiles, FA composition and lipogenetic genes expression in Tibetan sheep

Studies associated with regional roughage utilisation in Tibetan sheep have been limited. This study focussed on the mechanism of lipid metabolism and deposition in Tibetan sheep fed local roughage sources. Twenty-four Tibetan sheep weighing 16.1 ± 1.76 kg were randomly assigned to two mixed diets containing the same concentrate mixed with oat grass (OG) or highland barley straw (HBS). The ME and CP of OG diet were 7.16 MJ/kg DM and 5.94%, respectively, while in HBS diet were 7.13 MJ/kg DM and 7.39%. Lipid profiles in the plasma and liver, fatty acid (FA) composition and lipogenetic genes expression in the muscle and adipose tissue were determined. No difference was observed in DMI, total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein levels in the plasma and liver of sheep between two groups (p>.05). Plasma leptin and liver non-esterified fatty acid (NEFA) content in HBS group tended to be greater than that in OG group (p < .01). Sheep in HBS group had greater C18:2, C20:4, PUFA and PUFA/SFA ratio in the longissimus dorsi muscle (p < .05) and lower C17:0 (p = .05) and C20:1 (p < .01) in the perirenal adipose fat. Perirenal C18:0, C20:3 and C20:4 contents in HBS group tended to increase (p < .01). HBS stimulated the mRNA expression of SCD, C/EBPγ and SREBF1 in the muscle and FASN in the perirenal adipose fat (p < .01), but inhibited HSL, LPL, C/EBPγ and PPARγ expression in the perirenal adipose fat. These results indicated that replacement of OG by HBS promotes PUFA deposition in the muscle and long-chain FAs in the adipose fat of Tibetan sheep. Lipid deposition-related genes (SCD, FASN, HSL and LPL) and lipid metabolism regulators (C/EBPγ, SREBF1 and PPARγ) are involved in the transcriptional regulation.

Inhibitory activity of chokeberry, bilberry, raspberry and cranberry polyphenol-rich extract towards adipogenesis and oxidative stress in differentiated 3T3-L1 adipose cells.

Berries are a rich source of antioxidants and phytochemicals that have received considerable interest for their possible relations to human health. In this study, the anti-adipogenic effect of polyphenol-rich extract obtained from chokeberry Aronia melanocarpa (Michx.) Elliot, raspberry Rubus idaeus L., bilberry Vaccinium myrtillus L. and cranberry Vaccinium macrocarpon Aiton fruits and its underlying molecular mechanisms were investigated in differentiated 3T3-L1 adipose cells. Treatment with the extract (25–100 μg/mL) significantly decreased lipid accumulation and reactive oxygen species generation in adipocytes without showing cytotoxicity. Real-time PCR analysis revealed that the extract at a concentration of 100 μg/mL suppressed adipogenesis and lipogenesis via the down-regulation of PPARγ (67%), C/EBPα (72%), SREBP1 (62%), aP2 (24%), FAS (32%), LPL (40%), HSL (39%), and PLIN1 (32%) gene expression. Moreover, the extract significantly increased the expression of adiponectin (4.4-fold) and decreased leptin expression (90%) and respectively regulated the production of these adipokines in 3T3-L1 adipocytes. The obtained results suggest that the analyzed extract may be a promising source of bioactive compounds that support long-term weight maintenance and promote the effective management of obesity.

Maternal consumption of fish oil programs reduced adiposity in broiler chicks

Maternal intake of eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (22:6 n-3) has been associated with reduced adiposity in children, suggesting the possibility to program adipose development through dietary fatty acids before birth. This study determined if enriching the maternal diet in fish oil, the primary source of EPA and DHA, affected adipose development in offspring. Broiler chickens were used because they are obesity-prone, and because fatty acids provided to the embryo can be manipulated through the hen diet. Hens were fed diets supplemented (2.8% wt:wt) with corn oil (CO; n-6) or fish oil (FO; n-3) for 28 d. Chicks from both maternal diet groups were fed the same diet after hatch. Maternal FO consumption enriched chick adipose tissue in EPA and DHA and reduced adiposity by promoting more, but smaller, adipocytes. This adipocyte profile was paralleled by lower expression of the adipogenic regulator PPARG and its co-activator PPARGC1B, and elevated expression of LPL. Proteomics identified 95 differentially abundant proteins between FO and CO adipose tissue, including components of glucose metabolism, lipid droplet trafficking, and cytoskeletal organization. These results demonstrate that the maternal dietary fatty acid profile programs offspring adipose development.

Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (−1, −2 and −4) and FABPs (−1 and −3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR.

Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic \u03b2 cell proliferation after the withdrawal of OSI-906

Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28). On day 7, the visceral white fat mass was significantly reduced in mice treated with OSI-906 accompanied by a reduced expression of leptin and an increased expression of the lipolysis-related genes Lpl and Atgl. Interestingly, the lipoatrophy and the observed changes in gene expression were completely reversed on day 14. Similarly, liver steatosis and β cell proliferation were transiently observed on day 7 but had disappeared by day 14. Taken together, these results suggest that this model for the acute inhibition of systemic IR/IGF1R signaling may be useful for investigating the recovery from metabolic disorders induced by impaired growth factor signaling.

Effect of dietary fatty acid composition on growth, fatty acids composition and hepatic lipid metabolism in juvenile turbot (Scophthalmus maximus L.) fed diets with required n3 LC-PUFAs

A 12-week feeding experiment was conducted to investigate the effects of dietary fatty acids composition on growth performance, lipid deposition and some genes expression of hepatic lipid metabolism in juvenile turbot (Scophthalmus maximus L.) (mean initial body weight, 9.49±0.03g) fed diets with required n3 LC-PUFA. Juvenile turbot were fed diets with palm oil (PO), rapeseed oil (RO), soybean oil (SO) or linseed oil (LO) replacing the same levels of fish oil (FO), respectively. Each diet was randomly fed to triplicate tanks, and each tank was stocked with 35 fish. The results showed that growth performance and feed utilization of turbot fed diets with required n3 LC-PUFA were independent of dietary fatty acids composition. As expected, C16:0, C18:1n, C18:2n-6, C18:3n-3 and n3 LC-PUFAs level in liver were up to the maximum in the PO, RO, SO, LO and FO group, respectively, and significantly higher than that in the other groups (P<0.05). Fish fed the diet with RO had the lowest plasma triglyceride and the highest HDL-c/LDL-c, although no significant difference of plasma triglyceride had been found between the RO group and the LO group. Hepatic lipid content in fish fed diets with SO, RO, and LO was significantly higher compared with PO and FO groups. The higher activities of hepatic G6PD and ME were found in fish fed diets with PO or FO compared to LO. The relative expression of LPL, LXR, and ApoB-100 gene in the RO group and the LO group, MTP gene in the LO group, PPARα and FAS genes in the PO group, and PPARγ gene in the SO group were significantly higher than those in the FO group. These results indicated that the increase in hepatic lipid deposition of turbot induced by the SO, RO, and LO diets are associated with up-regulation of some genes involved in lipids biosynthesis metabolism.

Molecular aspects of lipid metabolism, digestibility and antioxidant status of Atlantic bluefin tuna (T. thynnus L.) larvae during first feeding

Atlantic bluefin tuna (Thunnus thynnus L.; ABT) larvae were fed on enriched rotifers Brachionus rotundiformis and copepod nauplii Acartia tonsa from first feeding to 15days post hatching. Rotifers were enriched with five different commercial products: OG, MG, AG and RA plus selenium and vitamin E. Copepods (COP) were cultured with the algae Rhodomonas baltica. Metabolic processes were studied by determining the expression of 30 genes related to lipid metabolism (transcription factors, fatty acid metabolism and lipid homeostasis), antioxidant enzymes, myogenesis and digestive enzymes. Growth and development parameters and high expression of myogenesis genes myhc2 and tropo indicated that COP were better than enriched rotifers as live prey for first feeding ABT. COP and AG-fed larvae showed the lowest values for the transcription factors pparγ and srebp2. The expression of fas showed differences among treatments, with highest relative expression in COP-fed larvae and those fed with RA rotifers. In relation to fatty acid catabolism, larvae fed RA had the highest aco expression levels, with the lowest observed in those fed COP. The expression profiles of lipid homeostasis genes showed that larvae fed COP had higher fabp2 and 4 expressions. Larvae fed AG showed the lowest lpl expression levels, with highest values observed in larvae fed OG. Regarding antioxidant enzyme gene expression, sod showed highest values in larvae fed COP and RA, with larvae fed MG rotifers showing lowest expression levels. A similar pattern was observed for the expression of cat and gpx1 and 4. The expression of genes for digestive enzymes showed that tryp expression levels were highest in COP-fed larvae but, in contrast, COP-fed larvae showed the lowest anpep and alp levels. ABT larvae fed AG displayed the lowest expression level of pla2. bal1 and bal2 presented similar expression patterns, with highest values in COP-fed ABT and lowest expression in larvae fed AG rotifers. Copepods were a superior live prey for first feeding ABT larvae compared to enriched rotifers, as indicated by the higher growth and flexion index achieved by COP-fed larvae, possibly reflecting the higher protein content of the copepods.

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.

Although the mechanisms linking obesity to insulin resistance (IR) and type 2 diabetes (T2D) are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR) or sensitive (OIS) adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT) in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in adipocytes in women independently of obesity. KFL15 and SLC25A10 are inhibitors of insulin-stimulated lipogenesis under conditions when glucose transport is the rate limiting step.

Irisin in goldfish (Carassius auratus): Effects of irisin injections on feeding behavior and expression of appetite regulators, uncoupling proteins and lipoprotein lipase, and fasting-induced changes in FNDC5 expression

Irisin is a peptide cleaved from the fibronectin type III domain containing protein 5 (FNDC5) gene that is secreted predominantly by muscle cells but also by other tissues including brain and intestine. In mammals, irisin has been shown to have thermogenic actions via the modulation of uncoupling proteins (UCPs) and to affect feeding and energy homeostasis via actions in brain, adipose tissue, liver, muscle and gastrointestinal tract. To examine the role of irisin on feeding and metabolism in fish, the effects of peripheral (intraperitoneal) injections of irisin on feeding behavior, glucose levels and the mRNA expressions of appetite regulators (cocaine and amphetamine regulated transcript CART, agouti related protein AgRP, orexin), UCPs and lipoprotein lipase LPL and brain factors (brain-derived neurotrophic factor , BDNF and tyrosine hydroxylase TH) were assessed in brain, white muscle and intestine. Irisin injections (100ng/g) induced a decrease in food intake and increases in brain orexin, CART1 and CART2, UCP2, BDNF, muscle UCP2 and intestine LPL mRNA expressions but did not affect blood glucose levels, brain AgRP, TH, UCP1, UCP3 and LPL or muscle UCP1, UCP3 and LPL expressions. A partial goldfish FNDC5 cDNA was isolated and the expressions of FDNC5, UCPs, LPL and BDNF were also compared between fed and fasted fish. Fasting induced decreases FNDC5 mRNA expression in the brain and intestine, but not in muscle. Fasting also induced increases in brain BDNF and LPL expressions and increases in UCP1, UCP2, UCP3 and LPL expressions in muscle. Our result suggest that irisin is an anorexigenic factor in fish and its actions might be in part mediated by appetite-regulating factors such as CART and orexins as well as UCP2 and brain factors such as BDNF.

Adipose tissue is influenced by hypoxia of obstructive sleep apnea syndrome independent of obesity

AimsObstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular risk and diabetes independent of obesity. We investigated whether adipose tissue dysfunction is exacerbated due to increased tissue hypoxia. MethodsAdipose tissue (AT) oxygenation was measured with a Clarke-type electrode (pATO2) in 16 men with OSAS before and after 4 months of continuous positive airway pressure therapy (CPAP) and in BMI-matched controls. Oxygenation was simultaneously monitored in arterial blood by pulse oximetry (SaO2); mixed blood in AT microcirculation by reflectance spectroscopy (SATO2) along with blood flow. Markers of hypoxia, adipo- and angiogenesis, inflammation and fibrosis were analysed in AT and serum. ResultsOSAS subjects were more insulin resistant. Despite lower arterial SaO2 (95.4±1.3% vs. 97.1±1.6%, P=0.013) in subjects with OSAS, there was no difference in the oxygen content of AT microcirculation (61.6±18.4 vs. 72.2±7.0%, P=0.07) or pATO2 (49.2±7.5 vs. 50.4±14.7mmHg, P=0.83) between groups. Resting AT blood flow was higher in OSAS compared to controls (108.5±22.7 vs. 78.9±24.9au, P<0.005) and strongly associated with inflammation markers IL-6 and MCP-1. AT of OSAS subjects showed increased inflammation (TNFA P=0.049) and fibrosis (COL3A1 P=0.02), a trend of higher HIF1A expression (P=0.06) and reduced adipogenesis (PPARG P=0.006). After CPAP, only expression of the lipid deposition marker LPL increased (30%, P=0.047). ConclusionsAdipose tissue of awake OSAS subjects appears no more hypoxic than adipose tissue of BMI-matched controls despite daytime hypoxaemia. Increased adipose tissue blood flow may be explained by an increased inflammatory response. We observe features of adipose dysfunction in subjects with OSAS, which attribute to increased cardiometabolic risk associated with this condition.

Response of genes involved in lipid metabolism in rat epididymal white adipose tissue to different fasting conditions after long-term fructose consumption

There has been much concern regarding the dietary fructose contributes to the development of metabolic syndrome. High-fructose diet changes the expression of genes involved in lipid metabolism. Levels of a number of hepatic lipogenic enzymes are increased by a high-carbohydrate diet in fasted-refed model rats/mice. Both the white adipose tissue (WAT) and the liver play a key role in the maintenance of nutrient homeostasis. Here, the aim of this study was to analyze the expression of key genes related to lipid metabolism in epididymal WAT (eWAT) in response to different fasting condition after long-term chronic fructose consumption. Rats were fed standard chow supplemented with 10% w/v fructose solution for 5 weeks, and killed after chow-fasting and fructose withdrawal (fasting) or chow-fasting and continued fructose (fructose alone) for 14 h. Blood parameters and the expression of genes involved in fatty acid synthesis (ChREBP, SREBP-1c, FAS, SCD1), triglyceride biosynthesis (DGAT-1, DGAT-2) and lipid mobilization (ATGL, HSL) in eWAT were analyzed. In addition, mRNA levels of PPAR-γ, CD36 and LPL were also detected. As expected, fructose alone increased the mRNA expression of FAS, SCD1, and correspondingly decreased ATGL and HSL mRNA levels. However, ChREBP, DGAT-2, ATGL and HSL mRNA levels restored near to normal while FAS and SCD1 tend to basic level under fasting condition. The mRNA expression of SREBP-1c, PPAR-γ and LPL did not changed at any situations but CD36 mRNA decreased remarkably in fructose alone group. In conclusion, these findings demonstrate that genes involved in lipid metabolism in rat eWAT are varied in response to different fasting conditions after long-term fructose consumption.

Effect of sex on the acute skeletal muscle response to sprint interval exercise.

What is the central question of this study? Are there sex-based differences in the acute skeletal muscle response to sprint interval training (SIT)? What is the main finding and its importance? In response to a SIT protocol that involved three 20s bouts of 'all-out' cycling, the expression of multiple genes associated with mitochondrial biogenesis, metabolic control and structural remodelling was largely similar between men and women matched for fitness. Our findings cannot explain previous reports of sex-based differences in the adaptive response to SIT and suggest that the mechanistic basis for these differences remains to be elucidated. A few studies have reported sex-based differences in response to several weeks of sprint interval training (SIT). These findings may relate to sex-specific responses to an acute session of SIT. We tested the hypothesis that the acute skeletal muscle response to SIT differs between sexes. Sedentary but healthy men (n = 10) and women (n = 9) were matched for age (22±3 versus 22±3years old) and cardiorespiratory fitness [45±7versus 43±10ml O2 (kg fat-free mass)-1 min-1 ], with women tested in the mid-follicular phase of their menstrual cycles. Subjects performed three 20s 'all-out' cycling efforts against a resistance of 5% of body mass, interspersed with 2min of recovery. Relative mean power outputs [7.6±0.5 versus 7.5±0.9W(kg fat-free mass)-1 ] were similar between men and women (P>0.05). Furthermore, there were no differences in the exercise-induced changes in mRNA expression of PGC-1α, PRC, PPARD, SIRT1, RIP140, HSL, HKII, PDK4, PDP1, FOXO3, MURF-1, Myf5, MyoD and VEGFA at 3h of recovery versus rest (P<0.05, main effect of time). The only sex-specific responses to exercise were an increase in the mRNA expression of GLUT4 and LPL in women only and Atrogin-1 in men only (P<0.05). Women also had higher expression of HKII and lower expression of FOXO3 compared with men (P<0.05, main effect of sex). We conclude that the acute skeletal muscle response to SIT is largely similar in young men and women. The mechanistic basis for sex-based differences in response to several weeks of SIT that has been previously reported remains to be elucidated.