Search Results (10)

The key fatty acid β-oxidation protein acetyl-CoA acyltransferase 2 (ACAA2) plays a significant role in myocardial lipid peroxidation and cardiac dysfunction induced by renal insufficiency. However, the mechanisms of lipid metabolism related to renal insufficiency-associated cardiac dysfunction remain poorly understood, and current clinical treatments have been largely ineffective. Through analysis of the Gene Expression Omnibus (GEO) database, we identified that the cardiac functional changes caused by renal insufficiency were primarily centered around the fatty acid β-oxidation signaling pathway, where ACAA2 plays a pivotal role in fatty acid β-oxidation, the tricarboxylic acid cycle, and ketone body metabolism. In an adenine-induced renal insufficiency mouse model, further examination with hematoxylin-eosin staining, Masson staining, and Oil Red O staining revealed alterations in the heart and kidney as well as the accumulation of lipid. Non-invasive blood pressure measurements and ultrasound images demonstrated improvements of peripheral vascular and right ventricular hemodynamic parameters with S-nitroso-L-cysteine (CSNO) inhalation therapy. In cell experiments, knocking down ACAA2 led to accumulation of lipid droplets and exacerbation of oxidative stress in cardiomyocytes, while overexpression of ACAA2 reversed these effects. The transcription factor FOXO4 was found to regulate lipid peroxidation by modulating ACAA2, and knocking down FOXO4 partially restored the expression of ACAA2, reducing oxidative stress in cardiomyocytes. Furthermore, exogenous CSNO effectively restored the expression of ACAA2 and reduced the level of FOXO4, thereby mitigating lipid peroxidation and improving cardiac function. Therefore, in the context of renal insufficiency, regulating the FOXO4–ACAA2 axis through CSNO inhalation therapy may provide a novel therapeutic strategy for alleviating myocardial lipid peroxidation and improving cardiac function. Full article

An analysis of the extent of the effect of steroidal saponin addition on glucose and lipid metabolism in hybrid grouper liver was performed at the transcriptomic and metabolomic levels. Feeds (52% crude protein, 14% crude lipid) were prepared containing 0% (S₀), 0.1% (S_0.1), and 0.2% (S_0.2) steroidal saponins. After eight weeks of feeding trial, compared to the S₀ group, the activities of serum albumin, alanine aminotransferase, and aspartate transaminase were significantly lower and the activities of lysozyme, acid phosphatase, and alkaline phosphatase were significantly higher in the S_0.1 group (p < 0.05). The superoxide dismutase, catalase, and glutathione peroxidase activities in the livers of the S_0.1 group were significantly higher than those of the S₀ group, while the malondialdehyde content was significantly lower than that of the S₀ group (p < 0.05). There were forty-two differentially expressed genes and thirty-two differential metabolites associated with glucose and lipid metabolism enriched using KEGG and GO. In the S₀ group, the expression of prostaglandin-endoperoxide synthase 1, prostaglandin E synthase 1, and thromboxane-2 synthase mRNA was significantly higher than in the S_0.1 group (p < 0.05). The expression levels of genes in the S₀ group were significantly higher than those in the S_0.1 group (p < 0.05), including for glycogen synthase kinase, glucose-6-phosphatase catalytic subunit 2, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, glucose transporter 4, and malate dehydrogenase. The expression of mRNA such as fatty acid synthase, acetyl-CoA carboxylase, and sterol regulatory element-binding protein 1 was significantly lower in the S_0.1 group than in the S₀ group, while the expression of carnitine acyltransferase 1, acyl-CoA synthetase, and acyl-CoA dehydrogenase genes was significantly higher in the S₀ group (p < 0.05). In summary, glycogen synthesis, gluconeogenesis, and the arachidonic acid metabolism pathway were inhibited by 0.1% steroidal saponins, and glycogenolysis, glycolysis, the tricarboxylic acid cycle, and the fatty acid β-oxidation pathway were activated. This study aims to provide a reference for the formulation of grouper feeds with a higher crude-lipid level. Full article

Zilpaterol hydrochloride (ZH) redistributes ingested energy and improves feed efficiency by increasing muscle mass and reducing fat in sheep and cattle carcasses in fattening; however, by increasing lipolysis and reducing intramuscular fat (IMF), it can affect meat quality in terms of the attributes of tenderness, juiciness, taste and color; in contrast, Zn methionine (ZM), due to its lipogenic effect, can improve meat marbling without affecting production efficiency. In the current study, 36 male Suffolk sheep were used (25 ± 0.58 kg live weight, LW) to evaluate the supply of ZH and ZM on growth, carcass traits, meat quality, fatty acid content and expression of genes which regulate the deposition of fatty acids (FA) in IMF. A completely randomized design was used, with factorial arrangement of 2 × 2 ZH (0 and 0.2 mg kg⁻¹ LW) and ZM (0 and 80 mg Zn kg⁻¹ dry matter, DM). The results showed that ZH increased (p < 0.05) carcass yield, compactness index and chop eye area and decreased greasing (p < 0.02). The content of ether extract in meat increased (p < 0.05) in sheep with ZM plus ZH, and in sheep with ZM (p < 0.01). ZH (p < 0.05) reduced (p < 0.02) the meat’s color index L*, a*, b*, C* and H*. The content in IMF of stearic (C18:0) and arachidic (C20:0) FA was reduced (p ≤ 0.05) by the effect of ZH, but the palmitoleic (C16:1), eicosatetraenoic (C20:4n6) and conjugated linoleic FA were increased (p ≤ 0.05) by the effect of ZH. ZM increased (p ≤ 0.05) palmitoleic (C16:1) and conjugated linoleic FA; the ZH interaction with ZM increased (p ≤ 0.05) linoleic (C18:2 c 9 c 12), linolenic (C18:3 c 9c12c15) and eicosatetraenoic (C20:4n6) FA. The ZH interaction with ZM influenced (p ≤ 0.05) the total saturated fatty acids (SFA), unsaturated fatty acids (UFA) and polyunsaturated fatty acids (PFA). ZH increased (p ≤ 0.05) the relative expression of mRNA from the enzymes lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), glycerol -3-phosphate acyltransferase (GPAT1) and diglyceride acyltransferase (DGAT1). ZM increased (p ≤ 0.05) the relative expression of mRNA from the enzyme gene acetyl-CoA carboxylase (ACC) and HSL, monoglyceride lipase (MGL). The ZM interaction with ZH increased (p ≤ 0.05) the relative expression of mRNA genes of the enzymes HSL and ACC. It was concluded that ZH improved feed conversion (FC), increased yield and reduced fat in carcasses; ZM increased IMF in Longissimus dorsi. ZH and ZM influenced the FA composition, reduced the SFA and increased the UFA and PFA; both additives also influenced the relative mRNA expression of genes involved in fatty acid metabolism. Full article

Walnut (Juglans regia L.) is an important woody oilseed tree species due to its commercial value. However, the regulation mechanism of walnut oil accumulation is still poorly understood, which restricted the breeding and genetic improvement of high-quality oil-bearing walnuts. In order to explore the metabolic mechanism that regulates the synthesis of walnut oil, we used transcriptome sequencing technology and metabolome technology to comprehensively analyze the key genes and metabolites involved in oil synthesis of the walnut embryo at 60, 90, and 120 days after pollination (DAP). The results showed that the oil and protein contents increased gradually during fruit development, comprising 69.61% and 18.32% of the fruit, respectively, during ripening. Conversely, the contents of soluble sugar and starch decreased gradually during fruit development, comprising 2.14% and 0.84%, respectively, during ripening. Transcriptome sequencing generated 40,631 unigenes across 9 cDNA libraries. We identified 51 and 25 candidate unigenes related to the biosynthesis of fatty acid and the biosynthesis of triacylglycerol (TAG), respectively. The expression levels of the genes encoding Acetyl-CoA carboxylase (ACCase), long-chain acyl-CoA synthetases (LACS), 3-oxoacyl-ACP synthase II (KASII), and glycerol-3-phosphate acyl transfer (GPAT) were upregulated at 60 DAP relative to the levels at 90 and 120 DAP, while the stearoyl-ACP-desaturase (SAD) and fatty acid desaturase 2 (FAD2) genes were highly abundantly expressed during all walnut developmental periods. We found that ABSCISIC ACID INSENSEITIVE3 (ABI3), WRINKLEDl (WRI1), LEAFY COTYLEDON1 (LEC1), and FUSCA3 (FUS3) may be key transcription factors involved in lipid synthesis. Additionally, the metabolomics analysis detected 706 metabolites derived from 18 samples, among which, 4 are implicated in the TAG synthesis, 2 in the glycolysis pathway, and 5 in the tricarboxylic acid cycle (TCA cycle) pathway. The combined analysis of the related genes and metabolites in TAG synthesis showed that phospholipid:diacylglycerol acyltransferase (PDAT) genes were highly abundantly expressed across walnut fruit developmental periods, and their downstream metabolite TAG gradually accumulated with the progression of fruit development. The FAD2 gene showed consistently higher expression during fruit development, and its downstream metabolites 18:2-PC and 18:3-PC gradually accumulated. The ACCase, LACS, SAD, FAD2, and PDAT genes may be crucial genes required for walnut oil synthesis. Our data will enrich public databases and provide new insights into functional genes related to lipid metabolism in walnut. Full article

Betaine is more efficient than choline and methionine methyl donors, as it can increase nitrogen storage, promote fat mobilisation and fatty acid oxidation and change body fat content and distribution. Lipid is absorbed primarily in the small intestine after consumption, which is also the basis of lipid metabolism. This study was conducted to establish a mouse model of obesity in Kunming mice of the same age and similar body weight, and to assess the effect of betaine on the intestinal protein expression profile of mice using a proteomic approach. Analysis showed that betaine supplementation reversed the reduction in expression of proteins related to lipid metabolism and transport in the intestine of mice induced by a high-fat diet (HFD). For example, the addition of betaine resulted in a significant upregulation of microsomal triglyceride transfer protein (Mttp), apolipoprotein A-IV (Apoa4), fatty-acid-binding protein 1 (Fabp1) and fatty-acid-binding protein 2 (Fabp2) expression compared to the HFD group (p < 0.05), which exhibited accelerated lipid absorption and then translocation from the intestine into the body’s circulation, in addition to a significant increase in Acetyl-CoA acyltransferase (Acaa1a) protein expression, hastening lipid metabolism in the intestine (p < 0.05). Simultaneously, a significant reduction in protein expression of alpha-enolase 1 (Eno1) as the key enzyme for gluconeogenesis in mice in the betaine-supplemented group resulted in a reduction in lipid synthesis in the intestine (p < 0.05). These findings provide useful information for understanding the changes in the protein profile of the small intestine in response to betaine supplementation and the potential physiological regulation of diets’ nutrient absorption. Full article

Dysregulation of de novo lipogenesis (DNL) has recently gained strong attention as being one of the critical factors that contribute to the assessment of non-alcoholic fatty liver disease (NAFLD). NAFLD is often diagnosed in patients with dyslipidemias and type 2 diabetes; thus, an interesting correlation can be deduced between high hematic free fatty acids and glucose excess in the DNL dysregulation. In the present study, we report that, in a cellular model of NAFLD, the coexistence of elevated glucose and FFA conditions caused the highest cellular lipid accumulation. Deepening the molecular mechanisms of the DNL dysregulation—RT-qPCR and immunoblot analysis demonstrated increased expression of mitochondrial citrate carrier (CiC), cytosolic acetyl-CoA carboxylase 1 (ACACA), and diacylglycerol acyltransferase 2 (DGAT2) involved in fatty acids and triglycerides synthesis, respectively. XBP-1, an endoplasmic reticulum stress marker, and SREBP-1 were the transcription factors connected to the DNL activation. Quercetin (Que), a flavonoid with strong antioxidant properties, and noticeably reduced the lipid accumulation and the expression of SREBP-1 and XBP-1, as well as of their lipogenic gene targets in steatotic cells. The anti-lipogenic action of Que mainly occurs through a strong phosphorylation of ACACA, which catalyzes the committing step in the DNL pathway. The high level of ACACA phosphorylation in Que-treated cells was explained by the intervention of AMPK together with the reduction of enzymatic activity of PP2A phosphatase. Overall, our findings highlight a direct anti-lipogenic effect of Que exerted through inhibition of the DNL pathway by acting on ACACA/AMPK/PP2A axis; thus, suggesting this flavonoid as a promising molecule for the NAFLD treatment. Full article

An alkaloid compound from the hairy root culture of Eurycoma longifolia has been isolated and characterised as 9-methoxycanthin-6-one. The aims of these studies were to investigate the in vitro anti-cancer activities of 9-methoxycanthin-6-one against ovarian cancer (A2780, SKOV-3), breast cancer (MCF-7), colorectal cancer (HT29), skin cancer (A375) and cervical cancer (HeLa) cell lines by using a Sulphorhodamine B assay, and to evaluate the mechanisms of action of 9-methoxycanthin-6-one via the Hoechst 33342 assay and proteomics approach. The results had shown that 9-methoxycanthin-6-one gave IC₅₀ values of 4.04 ± 0.36 µM, 5.80 ± 0.40 µM, 15.09 ± 0.99 µM, 3.79 ± 0.069 µM, 5.71 ± 0.20 µM and 4.30 ± 0.27 µM when tested in A2780, SKOV-3, MCF-7, HT-29, A375 and HeLa cell lines, respectively. It was found that 9-methoxycanthin-6-one induced apoptosis in a concentration dependent manner when analysed via the Hoechst 33342 assay. 9-methoxycanthine-6-one were found to affect the expressions of apoptotic-related proteins, that were proteins pyruvate kinase (PKM), annexin A2 (ANXA2), galectin 3 (LGAL3), heterogeneous nuclear ribonucleoprotein A1 (HNRNP1A1), peroxiredoxin 3 (PRDX3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the differential analysis of 2-DE profiles between treated and non-treated 9-methoxycanthine-6-one. Proteins such as acetyl-CoA acyltransferase 2 (ACAA2), aldehyde dehydrogenase 1 (ALDH1A1), capping protein (CAPG), eukaryotic translation elongation factor 1 (EEF1A1), malate dehydrogenase 2 (MDH2), purine nucleoside phosphorylase (PNP), and triosephosphate isomerase 1 (TPI1) were also identified to be associated with A2780 cell death induced by 9-methoxycanthine-6-one. These findings may provide a new insight on the mechanisms of action of 9-methoxycanthin-6-one in exerting its anti-cancer effects in vitro. Full article

Feeding frequency in one day is thought to be associated with nutrient metabolism and the physical development of the body in both experimental animals and humans. The present study was conducted to investigate transcriptomic responses in the liver and jejunal mucosa of pigs to evaluate the effects of different feeding frequencies on the body’s metabolism. Twelve Duroc × Landrance × Yorkshire growing pigs with an average initial weight (IW) of 14.86 ± 0.20 kg were randomly assigned to two groups: feeding one time per day (M1) and feeding two times per day (M2); each group consisted of six replicates (pens), with one pig per pen. During the one-month experimental period, pigs in the M1 group were fed on an ad libitum basis at 8:00 am; and the M2 group was fed half of the standard feeding requirement at 8:00 am and adequate feed at 16:00 pm. The results showed that average daily feed intake, average daily gain, feed:gain, and the organ indices were not significantly different between the two groups (p > 0.05). The total cholesterol (T-CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) concentrations in the serum, and the TG concentration in the liver in the M2 groups were significant lower than those in the M1 group, while the T-CHO concentration in the liver were significant higher in the M2 group (p < 0.05). Jejunal mucosa transcriptomic analysis showed the gene of Niemann-Pick C1-Like 1 (NPC1L1), Solute carrier family 27 member 4 (SLC27A4), Retinol binding protein 2 (RBP2), Lecithin retinol acyltransferase (LRAT), Apolipoprotein A (APOA 1, APOA 4, APOB, and APOC 3) were upregulated in the M2 group, indicating that fat digestion was enhanced in the small intestine, whereas Perilipin (PLIN1 and PLIN2) were downregulated, indicating that body fat was not deposited. Fatty acid binding proteins (FABPs) and Acetyl-CoA acyltransferase 1 (ACAA1) were upregulated in the M2 group, indicating that two times feeding daily could promote the oxidative decomposition of fatty acids. In conclusion, under the conditions in this study, the feeding frequency had no significant effect on the growth performance of pigs, but affected the body’s lipid metabolism, and the increase of feeding frequency promoted the fat digestion in the small intestine and the oxidative decomposition of fatty acids in the liver. Full article

Our previous studies showed that microRNA-15a (miR-15a) was closely related to intramuscular fat (IMF) deposition in chickens; however, its regulatory mechanism remains unclear. Here, we evaluated the expression characteristics of miR-15a and its relationship with the expression of acetyl-CoA acyltransferase 1 (ACAA1), acyl-CoA oxidase 1 (ACOX1) and sterol carrier protein 2 (SCP2) by qPCR analysis in Gushi chicken breast muscle at 6, 14, 22, and 30 weeks old, where we performed transfection tests of miR-15a mimics in intramuscular preadipocytes and verified the target gene of miR-15a in chicken fibroblasts (DF1). The miR-15a expression level at 30 weeks increased 13.5, 4.5, and 2.7-fold compared with the expression levels at 6, 14, and 22 weeks, respectively. After 6 days of induction, miR-15a over-expression significantly promoted intramuscular adipogenic differentiation and increased cholesterol and triglyceride accumulation in adipocytes. Meanwhile, 48 h after transfection with miR-15a mimics, the expression levels of ACAA1, ACOX1 and SCP2 genes decreased by 56.52%, 31.18% and 37.14% at the mRNA level in intramuscular preadipocytes. In addition, the co-transfection of miR-15a mimics and ACAA1, ACOX1 and SCP2 3′UTR (untranslated region) dual-luciferase vector significantly inhibited dual-luciferase activity in DF1 cells. Taken together, our data demonstrate that miR-15a can reduce fatty acid oxidation by targeting ACAA1, ACOX1, and SCP2, which subsequently indirectly promotes the differentiation of chicken intramuscular preadipocytes. Full article

Increasing the yield of plant oil is an important objective to meet the demand for sustainable resources and energy. Some attempts to enhance the expression of genes involved in oil synthesis in seeds have succeeded in increasing oil content. In many cases, the promoters of seed-storage protein genes have been used as seed-specific promoters. However, conventional promoters are developmentally regulated and their expression periods are limited. We constructed a chimeric promoter that starts to express in the early stage of seed development, and high-level expression is retained until the later stage by connecting the promoters of the biotin carboxyl carrier protein 2 (BCCP2) gene encoding the BCCP2 subunit of acetyl-CoA carboxylase and the fatty acid elongase 1 (FAE1) gene from Arabidopsis. The constructed promoter was ligated upstream of the TAG1 gene encoding diacylglycerol acyltransferase 1 and introduced into Arabidopsis. Seeds from transgenic plants carrying AtTAG1 under the control of the chimeric promoter showed increased oil content (up by 18–73%) compared with wild-type seeds. The novel expression profile of the chimeric promoter showed that this could be a promising strategy to manipulate the content of seed-storage oils and other compounds. Full article