Expression Of acetyl-CoA Carboxylase Research Articles

Hepatic Energy Metabolism Underlying Differential Lipidomic Responses to High-Carbohydrate and High-Fat Diets in Male Wistar Rats

BackgroundLow-carbohydrate diets are suggested to exert metabolic benefits by reducing circulating triacylglycerol (TG) concentrations, possibly by enhancing mitochondrial activity. ObjectiveWe aimed to elucidate mechanisms by which dietary carbohydrate and fat differentially affect hepatic and circulating TG, and how these mechanisms relate to fatty acid composition. MethodsSix-week-old, ∼300 g male Wistar rats were fed a high-carbohydrate, low-fat [HC; 61.3% of energy (E%) carbohydrate] or a low-carbohydrate, high-fat (HF; 63.5 E% fat) diet for 4 wk. Parameters of lipid metabolism and mitochondrial function were measured in plasma and liver, with fatty acid composition (GC), high-energy phosphates (HPLC), carnitine metabolites (HPLC-MS/MS), and hepatic gene expression (qPCR) as main outcomes. ResultsIn HC-fed rats, plasma TG was double and hepatic TG 27% of that in HF-fed rats. The proportion of oleic acid (18:1n–9) was 60% higher after HF vs. HC feeding while the proportion of palmitoleic acid (16:1n–7) and vaccenic acid (18:1n–7), and estimated activities of stearoyl-CoA desaturase, SCD-16 (16:1n–7/16:0), and de novo lipogenesis (16:0/18:2n–6) were 1.5–7.5-fold in HC vs. HF-fed rats. Accordingly, hepatic expression of fatty acid synthase (Fasn) and acetyl-CoA carboxylase (Acaca/Acc) was strongly upregulated after HC feeding, accompanied with 8-fold higher FAS activity and doubled ACC activity. There were no differences in expression of liver-specific biomarkers of mitochondrial biogenesis and activity (Cytc, Tfam, Cpt1, Cpt2, Ucp2, Hmgcs2); concentrations of ATP, AMP, and energy charge; plasma carnitine/acylcarnitine metabolites; or peroxisomal fatty acid oxidation. ConclusionsIn male Wistar rats, dietary carbohydrate was converted into specific fatty acids via hepatic lipogenesis, contributing to higher plasma TG and total fatty acids compared with high-fat feeding. In contrast, the high-fat, low-carbohydrate feeding increased hepatic fatty acid content, without affecting hepatic mitochondrial fatty acid oxidation.

THE SIMVASTATIN EFFECT ON ACETYL COA CARBOXYLASE1 AND FATTY ACID SYNTHASE GENE EXPRESSION IN RAT FED WITH HIGH FAT DIETS AND ITS ASSOCIATION WITH FATTY ACID PROPORTION AND CONCENTRATION

The aim of study was to determine the effect of different dosages of simvastatin on gene expression of Acetyl CoA Carboxylase 1 (ACC1) and Fatty Acid Synthase (FAS) in Wister rat hepatic tissues fed with high fat diets (HFD) and its association with serum fatty acid proportion and concentration. Four groups of rats (G1 to G4) were included. ACC1 and FAS expressions were analyzed by Real time quantitative polymerase chain reaction. Fatty acid concentration was measured by gas chromatography. There were significant differences when G4 versus G3, G4 and G3 versus G1 and G4 and G3 versus G2 was compared for total fatty acid concentration. The proportion of oleic acid to stearic acid showed significant decrease when G4 versus G3, G4 versus G2 and G4 versus G1 groups were compared, but the proportion of stearic acid to palmitic acid, linoleic acid to oleic acid (G3 versus G4) and oleic acid to palmitic acid in G4 increased when compared to G1, G2 and G3 groups. Treatment with simvastatin significantly increases or decreases some fatty acid ratio, serum fatty acid and total fatty acid concentrations. We also found that HFD led to no significant differences in ACC1 and FAS mRNA expression. Simvastatin increases proportion of linoleic acid to oleic acid, oleic acid to palmitic acid and oleic acid to stearic acid. Thus, statin therapy may be considered in prevention of cardiovascular and myocardial risk.

Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer.

Abnormal metabolism, including abnormal fatty acid metabolism, is an emerging hallmark of cancer. The current study sought to investigate the potential prognostic value of fatty acid metabolism-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). To this end, we obtained the gene expression data and clinical data of patients with CRC from The Cancer Genome Atlas (TCGA) database. Through gene set variation analysis (GSVA), we found that the fatty acid metabolism pathway was related to the clinical stage and prognosis of patients with CRC. After screening differentially expressed RNAs, we constructed a fatty acid metabolism-related competing endogenous RNA (ceRNA) network based on the miRTarBase, miRDB, TargetScan, and StarBase databases. Next, eight fatty acid metabolism-related lncRNAs included in the ceRNA network were identified to build a prognostic signature with Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, and a nomogram was established based on the lncRNA signature and clinical variables. The signature and nomogram were further validated by Kaplan–Meier survival analysis, Cox regression analysis, calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA). Besides, the TCGA internal and the quantitative real-time polymerase chain reaction (qRT-PCR) external cohorts were applied to successfully validate the robustness of the signature and nomogram. Finally, in vitro assays showed that knockdown of prognostic lncRNA TSPEAR-AS2 decreased the triglyceride (TG) content and the expressions of fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) in CRC cells, which indicated the important role of lncRNA TSPEAR-AS2 in modulating fatty acid metabolism of CRC. The result of Oil Red O staining showed that the lipid content in lncRNA TSPEAR-AS2 high expression group was higher than that in lncRNA TSPEAR-AS2 low expression group. Our study may provide helpful information for fatty acid metabolism targeting therapies in CRC.

Mentha cordifolia Leaf Extract Improves Hepatic Glucose and Lipid Metabolism in Obese Mice Fed with High-Fat Diet.

Mentha cordifolia (MC) is a popular herb used to flavor food in Thailand that exhibits several biological effects. The present study aimed to determine the role of MC in regulating glucose and lipid metabolism in mice fed a high-fat diet (HFD). ICR obese mice were fed an HFD (45 kcal% lard fat) for 12 weeks, with MC (100 and 200 mg/kg/d) treatment from Week 7. After treatment with MC for 6 weeks, mice showed significantly lower rates of hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increased amounts of serum adiponectin. Furthermore, in mice treated with MC, serum interleukin-6 and tumor necrosis factor alpha were significantly inhibited and liver histology results showed decreased lipid accumulation and liver triglyceride content vs. untreated mice. In addition, MC treatment was associated with smaller fat cells and lower gene expression of liver sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, and fatty acid synthase. However, MC treatment was associated with higher carnitine palmitoyltransferase 1a gene expression and significantly higher rates of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in liver, but lower levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. These results indicate MC regulates glucose and lipid metabolism in a HFD-induced obese mouse model, possibly via activation of AMPK signaling pathway.

Hormone-Sensitive Gene Signatures in the Mammary Epithelial Cells of Lactating Women With Persistent Low Milk Production

ObjectivesInsulin resistance may contribute to the association between maternal obesity and lactation difficulties. Our objective was to examine differential expression of genes involved in insulin-sensitive and prolactin-sensitive signaling in the mammary glands of women with very low, versus sufficient, milk production. MethodsAmong a subset of mothers in a study of low milk supply, extracellular mammary epithelial cell mRNA was isolated from fresh milk fat and submitted for RNA-sequencing. Aligned and quantified reads were examined for differentially expressed genes by t-test (DEG, p < 0.05 after false discovery rate adjustment). Insulin signaling and prolactin signaling KEGG pathways, in addition to a hand-curated gene list developed from relevant literature, were used for targeted DEG analysis. Sample size (milk volume range) for the sampled breast was n = 5 for the lowest milk production group [LMP] (0–53 mL/24 h), versus n = 4 for the highest milk production group [HMP] (422–463 mL/24 h). Clinical measures of metabolic health included BMI and fasting insulin and glucose. ResultsAll LMP samples were from mothers with obesity and with significantly elevated markers of insulin resistance versus the HMP group (e.g., HOMA-IR 1.7 versus 1.1, p < 0.05). DEG in the LMP group revealed significantly lower insulin-sensitive signaling, including a 2.3-fold decrease in insulin receptor substrate 2 (IRS2), versus HMP. There was no differential expression for genes involved in prolactin signaling, such as the prolactin receptor or JAK2. In LMP versus HMP groups, synthesis of beta-casein (CSN2) was 2.1-fold lower; expression of acetyl-CoA carboxylase 2 (ACACB), a gene downstream of insulin signaling that inhibits fatty acid oxidation, was 3.1-fold lower; and expression of UDP-glucose pyrophosphorylase 2 (UGP2), a rate-limiting gene in lactose synthesis and thus a determinant of milk volume, was 2.7-fold lower. ConclusionsSuppressed milk production by obese, LMP mothers is associated with downregulation of insulin-signaling genes but not hallmark prolactin-signaling genes. Overall, gene expression in the LMP group portrays an insulin-resistant signature in the mammary gland, with downregulation of insulin-sensitive anabolic processes and upregulation of catabolic gene expression. Funding SourcesNIH.

Use of 25-hydroxyvitamin D3 in diets for sows: A review.

Dietary supplementation with 25-hydroxyvitamin D3 (25OHD3), as an alternative source of vitamin D, is becoming increasingly popular due to its commercialization and more efficient absorbability. The addition of 25OHD3 rather than its precursor vitamin D3 can circumvent the 25-hydroxylation reaction in the liver, indicating that supplementation of 25OHD3 can rapidly improve the circulating vitamin D status of animals. Emerging experiments have reported that maternal 25OHD3 supplementation could increase sow performances and birth outcomes and promote circulating vitamin D status of sows and their offspring. Increased milk fat content was observed in many experiments; however, others demonstrated that adding 25OHD3 to lactating sow diets increased the contents of milk protein and lactose. Although an inconsistency between the results of different experiments exists, these studies suggested that maternal 25OHD3 supplementation could alter milk composition via its effects on the mammary gland. Previous studies have demonstrated that adding 25OHD3 to sow diets could improve the mRNA expressions of insulin-induced gene 1 (INSIG1) and sterol regulatory element-binding protein 1 (SREBP1) in the mammary gland cells from milk and increase the mRNA expressions of acetyl-CoA carboxylase α (ACCα) and fatty acid synthase (FAS) in the mammary gland tissue. Maternal 25OHD3 supplementation promotes skeletal muscle development of piglets before and after parturition, and improves bone properties including bone density and bone breaking force in lactating sows and their piglets. Interestingly, 25OHD3 supplementation in sow diets could improve neonatal bone development via regulation of milk fatty acid composition related to bone metabolism and mineralization. In this review, we also discuss the effects of adding 25OHD3 to sow diets on the gut bacterial metabolites of suckling piglets, and propose that butyrate production may be associated with bone health. Therefore, to better understand the nutritional functions of maternal 25OHD3 supplementation, this paper reviews advances in the studies of 25OHD3 for sow nutrition and provides references for practical application.

Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress.

Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). In this study, we found that blueberry-derived exosomes-like nanoparticles (BELNs) could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6 mice. Preincubation with BELNs decreased the level of reactive oxygen species (ROS), increased the mitochondrial membrane potential, and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1 (HO-1) and decreasing the content of Bax in rotenone-treated HepG2 cells. We also found that preincubation with BELNs accelerated the translocation of Nrf2, an important transcription factor of antioxidative proteins, from the cytoplasm to the nucleus in rotenone-treated HepG2 cells. Moreover, administration of BELNs improved insulin resistance, ameliorated the dysfunction of hepatocytes, and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice. Furthermore, BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice. These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.

The response of Trypanosoma brucei to Exogenous Fatty Acids in Low Lipid Conditions

Trypanosoma brucei is an extracellular parasite that causes African Sleeping Sickness and is endemic to the sub-Saharan African region. The parasite's extracellular nature forces the parasite to adapt to its host's environment. One of the regulatory mechanisms is to regulate fatty acid synthesis enzymes in response to exogenous fatty acids. Our previous study showed that the insect-host procyclic form (PF) T. brucei regulates the activity and expression level of acetyl-CoA carboxylase (ACC) when grown in media containing different lipid levels. PF in low lipid media has an elevated ACC activity but lower ACC protein level than in high lipid media. We also observed that the addition of C18:0 to PF in low lipid media reduced ACC activity and increased growth rate, which showed an environmental response to the exogenous fatty acid level. Here, we observe the growth and the ACC level of low lipid-adapted PF T. brucei after treatment with fatty acids of different chain lengths. We did not observe a significant change in the ACC protein level. However, we observed significant growth differences with the addition of different fatty acids, and some of these effects were cell density-dependent. These data suggested that the addition of fatty acids changes ACC's activity and PF growth pattern in low lipid, but does not change PF's ACC expression level. Future studies will investigate whether different fatty acids regulate ACC activity by phosphorylation, allosteric regulation, or a combination of both mechanisms.

Reduction of litter size during lactation in rats greatly influences fatty acid profiles in dams.

This study aimed to determine in lactating rats how fatty acid profiles are affected by litter size. On day 2 after parturition, litters of lactating rats were adjusted to a normal litter size of 9 pups/dam (NL) or to a small litter of 4 pups/dam (SL), and dams were studied at day 21 of lactation. Plasma glucose, insulin, and docosahexaenoic acid (DHA) concentrations were higher in SL than in NL dams, whereas the concentrations of most other fatty acids, triacylglycerols (TAG), and non-esterified fatty acids were lower in the SL dams. In the liver, the concentration of TAG was lower in SL than in NL dams as was the concentration of most fatty acids, with the exception of stearic acid (STA), arachidonic acid (ARA), and DHA concentrations that were higher in SL. Both plasma and liver Δ9 desaturase indices were lower in SL than in NL dams, whereas both Δ5 and Δ6 desaturase indices were higher in SL dams. In the liver, the expression of acetyl CoA carboxylase was lower in SL than in NL dams, and among the different adipose tissue depots, only mesenteric adipose tissue showed a higher concentration of most fatty acids in SL than in NL dams. It is proposed that reduction of litter size during lactation decreases liver lipogenesis de novo, although the synthesis of long-chain polyunsaturated fatty acids from their corresponding precursors increases, and lipolytic activity in mesenteric adipose tissue decreases probably as result of increased insulin responsiveness.

Galloyl Group in B-type Proanthocyanidin Dimers Was Responsible for Its Differential Inhibitory Activity on 3T3-L1 Preadipocytes due to the Strong Lipid Raft-Perturbing Potency.

The effects of three B-type proanthocyanidin (PA) dimers covering procyanidin B2 (B-0g), procyanidin B2 3'-O-gallate (B-1g), and procyanidin B2 3,3'-di-O-gallate (B-2g) on 3T3-L1 preadipocyte differentiation and the underlying mechanisms were investigated. The results showed that digalloylated B-type PA dimers (B-2g) strongly inhibited 3T3-L1 preadipocyte differentiation through disrupting the integrity of the lipid raft structure and inhibiting the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) and then downregulating the expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) factors, followed by B-1g, while B-0g had little effect. The different inhibitory effects were mainly due to the difference in the B-type PA dimer structure and the ability to interfere with lipid rafts. The greater the galloylation degree of B-type PA dimers, the stronger the ability to disrupt the lipid raft structure and oppose 3T3-L1 preadipocyte differentiation. In addition, galloylated B-type PA dimers had greater molecular hydrophobicity and topological polarity surface area and could penetrate into the lipid rafts to form multiple hydrogen bonds with the rafts by molecular dynamics simulation. These findings highlighted that the strong lipid raft-perturbing potency of galloylated B-type PA dimers was responsible for inhibition of 3T3-L1 preadipocyte differentiation.

Silibinin improves nonalcoholic fatty liver by regulating the expression of miR‑122: An invitro and invivo study.

Silibinin is a flavonoid that improves fatty liver and insulin resistance. To elucidate the effect of silibinin on lipid deposition and the potential molecular mechanism, the present study conducted in vivo and in vitro experiments. In the in vivo experiments, mice were randomly divided into control, high-fat and silibinin groups, while HepG2 cells were randomly divided into control, palmitic acid intervention and silibinin intervention groups. The mRNA, protein and miR-122 expression associated with hepatic lipid metabolism were detected in each group. The results demonstrated that silibinin reduced the triglyceride content, miR-122 expression and the mRNA and protein expressions of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). Silibinin increased the mRNA and protein expression of carnitine palmitoyl transferase 1A (CPT1A). In the present study, HepG2 cells cultured with palmitate were treated with silibinin following overexpression of micro RNA (miR) 122. The results demonstrated that the mRNA and protein expression of FAS and ACC was increased, while that of CPT1A was decreased. Therefore, it could be deduced that silibinin improved lipid metabolism by reducing the expression of miR-122 and inhibiting the expression of miR-122 may be a new therapeutic target to improve fatty liver disease.

Recombinant overexpression of the Escherichia coli acetyl-CoA carboxylase gene in Synechocystis sp. boosts lipid production.

Microalgae have received continued attention as a potential source for biofuel production. However, the lack of suitable strains that provide a lipid-rich biomass and tolerate harsh condition inhibits their industrial application. This report describes an effort to transform Synechocystis sp. with genes encoding acetyl-CoA carboxylase (ACC), a key regulatory enzyme in the lipogenesis pathway, from the white mustard plant (Sinapis alba) and the bacterium Escherichia coli DH5α using chitosan nanoparticles. Although a recombinant plasmid encoding S. alba ACC failed to express, successful transformation was achieved with a recombinant plasmid encoding E. coli DH5α ACC. The successful transformant, Synechocystis sp. PAK13, exhibited increased ACC expression compared with its wild-type parent (11.8 vs. 7.2 ng), which significantly increased its lipid content (by 3.6-fold). Synechocystis sp. PAK13 also exhibited a significant (20%) reduction in photosynthetic pigments, a 1.52-fold higher glucose content and a 3.5-fold lower sucrose content than the wild-type. In conclusion, this report introduces a useful strategy to overexpress the ACC gene in microalgae, creating strains with improved lipid production that are suited to industrial applications.

Triphenyl phosphate disturbs the lipidome and induces endoplasmic reticulum stress and apoptosis in JEG-3 cells

Triphenyl phosphate (TPP) is a frequently used aryl organophosphate flame retardant. Epidemiological studies have shown that TPP and its metabolite diphenyl phosphate (DPP) can accumulate in the placenta, and positively correlated with abnormal birth outcomes. TPP can disturb placental hormone secretion through the peroxisome proliferator-activated receptor γ (PPARγ) pathway. However, the extent and mechanism of placental toxicity mediation by TPP remains unknown. In this study, we used JEG-3 cells to investigate the role of PPARγ-regulated lipid metabolism in TPP-mediated placental toxicity. The results of lipidomic analysis showed that TPP increased the production of triglycerides (TG), fatty acids (FAs), and phosphatidic acid (PA), but decreased the levels of phosphatidylethanol (PE), phosphatidylserine (PS), and sphingomyelin (SM). TG accumulation was accompanied by increased levels of sterol regulatory element binding transcription factor 1 (SREBP1), acetyl-coA carboxylase (ACC), and fatty acid transport protein (CD36). Although PPARγ and its target CCAAT/enhancer binding proteins (C/EBPα) was decreased, the TG content and gene expression of SREBP1, ACC, and CD36 decreased when TPP was co-exposed to the PPARγ antagonist GW9662. TPP also induced inflammatory responses, endoplasmic reticulum stress (ERS), and cell apoptosis. Expression of genes related to ERS and apoptosis were attenuated by GW9662. Together, these results show that TPP can disturb lipid metabolism and cause lipid accumulation through PPARγ, induce ERS, and cell apoptosis. Our findings reveal that the developmental toxicity of TPP through placental toxicity should not be ignored.

Two promoters of biodiesel and biomass production induced by different concentrations of myo-inositol in Chlorella vulgaris

Microalgae are a large group of phototrophic microorganisms that convert CO2 into biomass, which can be used as an important source of biofuels. Biofuels have a lot of interesting applications in various industries. The main objective of the current study was to assess the biomass and lipid production, gene expression of acetyl-CoA carboxylase (accD) and ribulose bisphosphate carboxylase large-chain (rbcL), and the lipid content produced by myo-inositol treatment in the microalga Chlorella vulgaris. Three different myo-inositol concentrations (i.e., 50, 100, and 200 mg/L) were added to the algal growth media, and the algal cells were sampled on the day of entering the stationary phase of the growth cycle. Biomass production was increased by increasing the supplement. However, the 200 mg/L concentration of myo-inositol was critical for lipid production. To evaluate the effect of the vitamin on the expression of the accD and rbcL genes, real-time PCR was used. The rbcL gene expression increased in relation to biomass production, i.e., 224.08 times higher than the control. On the other hand, the accD expression at 200 mg/L myo-inositol concentration, as physiological stress, increased, i.e., 95.2 times higher than the control. Therefore, this growth complement can induce biomass and lipid production. Findings of the present study provide valuable insight into determining the biochemical modulation strategies of biomass and lipid production. In this study, two separate controlling systems and two independent promoters were proposed to regulate the transcription of rbcL and accD genes induced by various concentrations of myo-inositol.

UV-Induced Reduction of ACVR1C Decreases SREBP1 and ACC Expression by the Suppression of SMAD2 Phosphorylation in Normal Human Epidermal Keratinocytes.

Activin A receptor type 1C (ACVR1C), a type I transforming growth factor-β (TGF-β) receptor, has been implicated in sensitive skin and psoriasis and is involved in the regulation of metabolic homeostasis as well as cell proliferation and differentiation. In this study, we identified a novel role of ACVR1C in the ultraviolet (UV)-irradiation-induced reduction of epidermal lipogenesis in human skin. UV irradiation decreased ACVR1C expression and epidermal triglyceride (TG) synthesis in human skin in vivo and in primary normal human epidermal keratinocytes (NHEK) in vitro. Lipogenic genes, including genes encoding acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein-1 (SREBP1), were significantly downregulated in UV-irradiated NHEK. ACVR1C knockdown by shRNA resulted in greater decreases in SREBP1 and ACC in response to UV irradiation. Conversely, the overexpression of ACVR1C attenuated the UV-induced decreases in SREBP1 and ACC. Further mechanistic study revealed that SMAD2 phosphorylation mediated the ACVR1C-induced lipogenic gene modulation. Taken together, a decrease in ACVR1C may cause UV-induced reductions in SREBP1 and ACC as well as epidermal TG synthesis via the suppression of SMAD2 phosphorylation. ACVR1C may be a target for preventing or treating UV-induced disruptions in lipid metabolism and associated skin disorders.

Metabolic programming of adipose tissue in female C57Bl 6 mice offspring by maternal high fat feeding and obesity results in greater adaptability to dietary fat content and resistance to high fat diet-induced glucose intolerance compared to male mice

Maternal lifestyle influence may be a factor in the worldwide prevalence of obesity and its complications, including diabetes. Studies investigating the effect of the perinatal maternal environment have produced a range of results, sometimes diametrically opposite. The present study was designed to investigate how obesity and weight gain in pregnant mice affects energy balance, body composition and glucose homeostasis in their offspring, both at a young age on standard diet and when older and fed a high-fat diet. At six weeks of age both male and female offspring from mothers fed a high fat diet had a shorter body length than those from mothers fed standard chow. In contrast to males, female offspring also contained a higher proportion of fat and had elevated circulating leptin and adiponectin. Their gonadal fat pads were heavier and contained larger adipocytes, whereas male offspring had proportionally more smaller adipocytes. Six-week-old female, but not male, offspring had increased gonadal fat gene expression of acetyl CoA carboxylase 1, the rate-limiting step in lipid biosynthesis, and decreased gene expression of carnitine palmitoyl transferase 1, the rate-limiting step in fatty acid oxidation. Maternal high fat diet had no effect on glucose tolerance in six-week-old mice, but this was achieved with higher insulin levels in females. Contrastingly, when the offspring were fed a high fat diet for three months, female, but not male, offspring were leaner than those from mothers fed standard chow. Their gonadal fat depots were lighter and the adipocytes were smaller. Female, but not male, offspring fed high fat diet had decreased gonadal fat gene expression of acetyl CoA carboxylase 1, and increased gene expression of carnitine palmitoyl transferase 1. High fat diet-induced glucose intolerance and elevated plasma insulin concentration were improved in female, but not male, offspring. Plasma leptin and adiponectin remained higher in female offspring on high fat diet with resistin levels being lower. These results suggest that the gonadal fat of female offspring is more adaptable to different levels of dietary fat exposure, increasing storage when levels are low and increasing oxidation when levels are high. This may help female offspring be more resistant to the detrimental effects of high fat diet than male mice.

Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes.

Cudratricusxanthone A (CTXA) is a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclear. In this study, we investigated the effects of CTXA on lipid accumulation and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, two known inflammatory enzymes, in 3T3-L1 preadipocytes. Strikingly, CTXA at 10 µM markedly inhibited lipid accumulation and reduced triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. On mechanistic levels, CTXA at 10 µM suppressed not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, but also phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during 3T3-L1 preadipocyte differentiation. In addition, CTXA at 10 µM up-regulated phosphorylation levels of cAMP-activated protein kinase (AMPK) while down-regulating expression and phosphorylation levels of acetyl-CoA carboxylase (ACC) during 3T3-L1 preadipocyte differentiation. Moreover, CTXA at 10 µM greatly attenuated tumor necrosis factor (TNF)-α-induced expression of iNOS, but not COX-2, in 3T3-L1 preadipocytes. These results collectively demonstrate that CTXA has strong anti-adipogenic and anti-inflammatory effects on 3T3-L1 cells through control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, STAT-3/5, AMPK, and iNOS.

Ghrelin, via corticotropin-releasing factor receptors, reduces glucose uptake and increases lipid content in mouse myoblasts cells.

Ghrelin and the corticotropin‐releasing factor (CRF) family are known regulators of cellular metabolism and energy balance. We previously demonstrated that myoblast glucose metabolism is regulated by ghrelin and that this effect is mediated by CRF receptor type 2 (CRF‐R2). Here we explored the effect of des‐acyl ghrelin, the major circulating isoform of ghrelin, on cellular metabolism in mouse myoblast C2C12 cells, and examined whether CRF family receptors mediate its metabolic effects in muscle cells. C2C12 cells were exposed to des‐acyl ghrelin with or without the CRF‐R1‐ and CRF‐R2‐specific antagonists antalarmin or antisauvagine‐30, respectively. Des‐acyl ghrelin reduced glucose uptake and expression of the glucose transporter GLUT4, but induced retinol‐binding protein 4 (RBP4) expression. Antalarmin and antisauvagine‐30 inhibited the induction of glucose uptake by des‐acyl ghrelin and its effect on GLUT4 and RBP4 expression. Moreover, treating C2C12 cells with des‐acyl ghrelin resulted in cAMP activation in response to the CRF‐R1‐specific ligand stressin, and the CRF‐R2‐specific ligand Ucn3. Furthermore, des‐acyl ghrelin reduced the expression of uncoupling proteins UCP2 and UCP3. Adding antalarmin or antisauvagine‐30 to the medium reversed this effect. Finally, des‐acyl ghrelin elevated lipid content and acetyl‐CoA carboxylase expression in C2C12 cells. Our results suggest that during food deprivation, des‐acyl ghrelin signals the muscle cells that glucose levels are low and that they should switch to fatty acids for their metabolic fuel.

Growth performance, meat quality and lipid metabolism in finishing lambs fed diets containing rumen-unprotected and rumen-protected betaine

This study investigated the influence of dietary supplementation of rumen-unprotected betaine (RUPB) and rumen-protected betaine (RPB) on growth performance, meat quality and fatty acid profile in intramuscular and subcutaneous fat of growing lambs. A total of 24 Hu male lambs were equally divided into three groups and fed a basal diet or basal diet supplemented with 1.6 g/kg of RUPB or 2.9 g/kg of RPB for 68 days. The water loss, redness of longissimus dorsi (LD) muscle and abdominal fat percentage were reduced in RUPB and RPB groups (p < .05). RPB supplementation decreased the shear force of LD muscle (p < .05). Polyunsaturated fatty acid (PUFA) content in LD muscle was decreased in RPB group, whereas n-3PUFA content was increased in RUPB group (p < .05). RUPB and RPB supplementation reduced the content of saturated fatty acid (SFA), and increased the contents of PUFA, monounsaturated fatty acid (MUFA), and n-6PUFA in subcutaneous fat (p < .05). Furthermore, dietary RUPB and RPB supplementation increased the mRNA expression of acetyl-CoA carboxylase (ACC) and glycerol-3-phosphate acyltransferase 1 (GPAT1) in LD muscle (p<.05); it increased the mRNA expression of fatty acid synthetase (FANS) and lipoprotein lipase (LPL) but reduced the mRNA expression of GPAT1 in subcutaneous fat (p < .05). In conclusion, either RUPB or RPB supplementation may improve the meat quality and slightly change the fat deposition and fatty acid composition of intramuscular and subcutaneous fat, and RUPB is recommended as a supplement for growing male lambs based on its lower cost. Highlights Dietary supplementation of both rumen-unprotected betaine and (RUPB) and rumen-protected betaine (RPB) improved meat quality and altered the fat deposition of growing male lambs. Both RUPB and RPB supplementation changed fatty acid composition in the longissimus dorsi muscle and subcutaneous adipose tissue. RUPB is recommended as a supplement for growing lambs based on its lower cost.

뽕잎 추출물 기원 Flavonoid Rich Fraction의 항비만효과

Background: This study investigated the anti-obesity effect of the flavonoid rich fraction (FRF) and its constituent, rutin obtained from the leaf of Morus alba L., on the lipid accumulation mechanism in 3T3-L1 adipocyte and C57BL/6 mouse models.BRMethods and Results: In Oil Red O staining, FRF (1,000 ㎍/㎖) treatments showed inhibition rate of 35.39% in lipid accumulation compared to that in the control. AdipoRedTM assay indicated that the triglyceride content in 3T3-L1 adipocytes treated with FRF (1,000 ㎍/㎖) was reduced to 23.22%, and free glycerol content was increased to 106.04% that of the control. FRF and its major constituent, rutin affected mRNA gene expression. Rutin contributed to the inhibition of Sterol regulatory element binding protein-1c (SREBP-1c) gene expression, and inhibited the transcription factors SREBP-1c, peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, the effect of FRF administration on obesity development in C57BL/6 mice fed high-fat diet (HFD) was investigated. FRF suppressed weight gain, and reduced liver triglyceride and leptin secretion. FRF exerted potential anti-inflammatory effects by improving insulin resistance and adiponectin levels, and could thus be used to help counteract obesity. The mRNA expressions of PPAR-γ, FAS, ACC, and CPT-1 were determined in liver tissue. Quantitative real-time PCR analysis was also performed to evaluate the expression of IL-1β, IL-6, and TNF-α in epididymal adipose tissue. Compared to the control group, mice fed the HFD showed the up-regulation in PPAR-γ, FAS, IL-6, and TNF-α genes, and down-regulation in CPT1 gene expression. FRF treatement markedly reduced the expression of PPAR-γ, FAS, IL-6, and TNF-α compared to those in HFD control, whereas increased the expression level of CPT1.BRConclusions: These results suggest that the FRF and its major active constituent, rutin, can be used as effective anti-obesity agents.