The Saccharomyces cerevisiae Spo7 basic tail is required for Nem1-Spo7/Pah1 phosphatase cascade function in lipid synthesis.

The Saccharomyces cerevisiae Nem1-Spo7 protein phosphatase complex dephosphorylates and thereby activates Pah1 at the nuclear/endoplasmic reticulum membrane. Pah1, a phosphatidate phosphatase catalyzing the dephosphorylation of phosphatidate to produce diacylglycerol, is one of the most highly regulated enzymes in lipid metabolism. The diacylglycerol produced in the lipid phosphatase reaction is utilized for the synthesis of triacylglycerol that is stored in lipid droplets. Disruptions of the Nem1-Spo7/Pah1 phosphatase cascade cause a plethora of physiological defects. Spo7, the regulatory subunit of the Nem1-Spo7 complex, is required for the Nem1 catalytic function and interacts with the acidic tail of Pah1. Spo7 contains three conserved homology regions (CR1-3) that are important for the interaction with Nem1, but its region for the interaction with Pah1 is unknown. Here, by deletion and site-specific mutational analyses of Spo7, we revealed that the C-terminal basic tail (residues 240-259) containing five arginine and two lysine residues is important for the Nem1-Spo7 complex-mediated dephosphorylation of Pah1 and its cellular function (triacylglycerol synthesis, lipid droplet formation, maintenance of nuclear/endoplasmic reticulum membrane morphology, and cell growth at elevated temperatures). The glutaraldehyde cross-linking analysis of synthetic peptides indicated that the Spo7 basic tail interacts with the Pah1 acidic tail. This work advances our understanding of the Spo7 function and the Nem1-Spo7/Pah1 phosphatase cascade in yeast lipid synthesis.

Multiple transcription factors of Arabidopsis thaliana that are activated by LEAFY COTYLEDON 2 regulate triacylglycerol biosynthesis.

Plant triacylglycerols (TAG) are used in food and various industrial feedstocks. LEAFY COTYLEDON 2 (LEC2), a master positive regulator of TAG biosynthesis, regulates a complex network of transcription factors (TFs) during seed development. Aside from WRINKLED1 (WRI1), the TFs regulated by LEC2 related to TAG biosynthesis have not yet been identified. Previously, we identified 25 seed-expressing TFs that were upregulated in Arabidopsis leaves that overexpressed senescence-induced LEC2. In this study, each of the 25 TFs was transiently expressed in the leaves of Nicotiana benthamiana to identify unknown TFs that regulate TAG biosynthesis. The TAG content of the transformed leaves was analyzed using thin layer chromatography and gas chromatography. We observed that five TFs, ARABIDOPSIS RESPONSIVE REGULATOR 21 (ARR21), AINTEGUMENTA-LIKE 6 (AIL6), APETALA2/ETHYLENE RESPONSIVE FACTOR 55 (ERF55), WRKY DNA-BINDING PROTEIN 8 (WRKY8), and ARABIDOPSIS NAC DOMAIN CONTAINING PROTEIN 38 (ANAC038) increased TAG synthesis in the leaves. Among these, the promoters of AIL6, ERF55, WRKY8, and ANAC038 contain RY motifs, which are LEC2-binding sites activated by LEC2. AIL6 overexpression in Arabidopsis increased the total fatty acid (FA) content in seeds and altered the FA composition, with increases in 16:0, 18:1, and 18:2 and decreases in 18:0, 18:3, and 20:1 compared with those in the wild type (WT). AIL6 overexpression activates several FA and TAG biosynthesis genes. Therefore, our study successfully identified several new TFs regulated by LEC2 in TAG biosynthesis and showed that AIL6 increased the TAG content in seeds.

Identification of a 1-acyl-glycerol-3-phosphate acyltransferase from Mycobacterium tuberculosis, a key enzyme involved in triacylglycerol biosynthesis.

Latent tuberculosis, caused by dormant Mycobacterium tuberculosis (Mtb), poses a threat to global health through the incubation of undiagnosed infections within the community. Dormant Mtb, which is phenotypically tolerant to antibiotics, accumulates triacylglycerol (TAG) utilizing fatty acids obtained from macrophage lipid droplets. TAG is vital to mycobacteria, serving as a cell envelope component and energy reservoir during latency. TAG synthesis occurs by sequential acylation of glycerol-3-phosphate, wherein the second acylation step is catalyzed by acylglycerol-3-phosphate acyltransferase (AGPAT), resulting in the production of phosphatidic acid (PA), a precursor for the synthesis of TAG and various phospholipids. Here, we have characterized a putative acyltransferase of Mtb encoded by Rv3816c. We found that Rv3816c has all four characteristic motifs of AGPAT, exists as a membrane-bound enzyme, and functions as 1-acylglycerol-3-phosphate acyltransferase. The enzyme could transfer the acyl group to acylglycerol-3-phosphate (LPA) from monounsaturated fatty acyl-coenzyme A of chain length 16 or 18 to produce PA. Complementation of Escherichia coli PlsC mutant in vivo by Rv3816c confirmed that it functions as AGPAT. Its active site mutants, H43A and D48A, were incapable of transferring the acyl group to LPA in vitro and were not able to rescue the growth defect of E. coli PlsC mutant in vivo. Identifying Rv3816c as AGPAT and comparing its properties with other AGPAT homologs is not only a step toward understanding the TAG biosynthesis in mycobacteria but has the potential to explore it as a drug target.

Identification of key genes for triacylglycerol biosynthesis and storage in herbaceous peony (Paeonia lactifolra Pall.) seeds based on full-length transcriptome.

BACKGROUND: The herbaceous peony (Paeonia lactiflora Pall.) is extensively cultivated in China due to its root being used as a traditional Chinese medicine known as 'Radix Paeoniae Alba'. In recent years, it has been discovered that its seeds incorporate abundant unsaturated fatty acids, thereby presenting a potential new oilseed plant. Surprisingly, little is known about the full-length transcriptome sequencing of Paeonia lactiflora, limiting research into its gene function and molecular mechanisms. RESULTS: A total of 484,931 Reads of Inserts (ROI) sequences and 1,455,771 full-Length non-chimeric reads (FLNC) sequences were obtained for CDS prediction, TF analysis, SSR analysis and lncRNA identification. In addition, gene function annotation and gene structure analysis were performed. A total of 4905 transcripts were related to lipid metabolism biosynthesis pathway, belonging to 28 enzymes. We use these data to identify 10 oleosin (OLE) and 5 diacylglycerol acyltransferase (DGAT) gene members after de-redundancy. The analysis of physicochemical properties and secondary structure showed them similarity in gene family respectively. The phylogenetic analysis showed that the distribution of OLE and DGAT family members was roughly the same as that of Arabidopsis. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed expression changes in different seed development stages, and showed a trend of increasing and then decreasing. CONCLUSION: In summary, these results provide new insights into the molecular mechanism of triacylglycerol (TAG) biosynthesis and storage during the seedling stage in Paeonia lactiflora. It provides theoretical references for selecting and breeding oil varieties and understanding the functions of oil storage as well as lipid synthesis related genes in Paeonia lactiflora.

Nitrogen starvation leads to TOR kinase-mediated downregulation of fatty acid synthesis in the algae Chlorella sorokiniana and Chlamydomonas reinhardtii.

BACKGROUND: When subject to stress conditions such as nutrient limitation microalgae accumulate triacylglycerol (TAG). Fatty acid, a substrate for TAG synthesis is derived from de novo synthesis or by membrane remodeling. The model industrial alga Chlorellasorokiniana accumulates TAG and other storage compounds under nitrogen (N)-limited growth. Molecular mechanisms underlying these processes are still to be elucidated. RESULT: Previously we used transcriptomics to explore the regulation of TAG synthesis in C. sorokiniana. Surprisingly, our analysis showed that the expression of several key genes encoding enzymes involved in plastidic fatty acid synthesis are significantly repressed. Metabolic labeling with radiolabeled acetate showed that de novo fatty acid synthesis is indeed downregulated under N-limitation. Likewise, inhibition of the Target of Rapamycin kinase (TOR), a key regulator of metabolism and growth, decreased fatty acid synthesis. We compared the changes in proteins and phosphoprotein abundance using a proteomics and phosphoproteomics approach in C. sorokiniana cells under N-limitation or TOR inhibition and found extensive overlap between the N-limited and TOR-inhibited conditions. We also identified changes in the phosphorylation status of TOR complex proteins, TOR-kinase, and RAPTOR, under N-limitation. This indicates that TOR signaling is altered in a nitrogen-dependent manner. We find that TOR-mediated metabolic remodeling of fatty acid synthesis under N-limitation is conserved in the chlorophyte algae Chlorella sorokiniana and Chlamydomonas reinhardtii. CONCLUSION: Our results indicate that under N-limitation there is significant metabolic remodeling, including fatty acid synthesis, mediated by TOR signaling. This process is conserved across chlorophyte algae. Using proteomic and phosphoproteomic analysis, we show that N-limitation affects TOR signaling and this in-turn affects the metabolic status of the cells. This study presents a link between N-limitation, TOR signaling and fatty acid synthesis in green-lineage.

Biochemical characterization of acyl-CoA:diacylglycerol acyltransferase2 from the diatom Phaeodactylum tricornutum and its potential effect on LC-PUFAs biosynthesis in planta.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), belonging to ω-3 long-chain polyunsaturated fatty acids (ω3-LC-PUFAs), are essential components of human diet. They are mainly supplemented by marine fish consumption, although their native producers are oleaginous microalgae. Currently, increasing demand for fish oils is insufficient to meet the entire global needs, which puts pressure on searching for the alternative solutions. One possibility may be metabolic engineering of plants with an introduced enzymatic pathway producing ω3-LC-PUFAs. RESULT: In this study we focused on the acyl-CoA:diacylglycerol acyltransferase2b (PtDGAT2b) from the diatom Phaeodactylum tricornutum, an enzyme responsible for triacylglycerol (TAG) biosynthesis via acyl-CoA-dependent pathway. Gene encoding PtDGAT2b, incorporated into TAG-deficient yeast strain H1246, was used to confirm its activity and conduct biochemical characterization. PtDGAT2b exhibited a broad acyl-CoA preference with both di-16:0-DAG and di-18:1-DAG, whereas di-18:1-DAG was favored. The highest preference for acyl donors was observed for 16:1-, 10:0- and 12:0-CoA. PtDGAT2b also very efficiently utilized CoA-conjugated ω-3 LC-PUFAs (stearidonic acid, eicosatetraenoic acid and EPA). Additionally, verification of the potential role of PtDGAT2b in planta, through its transient expression in tobacco leaves, indicated increased TAG production with its relative amount increasing to 8%. Its co-expression with the gene combinations aimed at EPA biosynthesis led to, beside elevated TAG accumulation, efficient accumulation of EPA which constituted even 25.1% of synthesized non-native fatty acids (9.2% of all fatty acids in TAG pool). CONCLUSIONS: This set of experiments provides a comprehensive biochemical characterization of DGAT enzyme from marine microalgae. Additionally, this study elucidates that PtDGAT2b can be used successfully in metabolic engineering of plants designed to obtain a boosted TAG level, enriched not only in ω-3 LC-PUFAs but also in medium-chain and ω-7 fatty acids.

The synthesis of triacylglycerol by diacylglycerol acyltransferases (CsDGAT1A and CsDGAT2D) is essential for tolerance of cucumber's resistance to low-temperature stress.

KEY MESSAGE: CsDGAT1A and CsDGAT2D play a positive regulatory role in cucumber's response to low-temperature stress and positively regulate the synthesis of triacylglycerol (TAG). Triacylglycerol (TAG), a highly abundant and significant organic compound in plants, plays crucial roles in plant growth, development, and stress responses. The final acetylation step of TAG synthesis is catalyzed by diacylglycerol acyltransferases (DGATs). However, the involvement of DGATs in cucumber's low-temperature stress response remains unexplored. This study focused on two DGAT genes, CsDGAT1A and CsDGAT2D, investigating their function in enhancing cucumber's low-temperature stress tolerance. Our results revealed that both proteins were the members of the diacylglycerol acyltransferase family and were predominantly localized in the endoplasmic reticulum. Functional analysis demonstrated that transient silencing of CsDGAT1A and CsDGAT2D significantly compromised cucumber's low-temperature stress tolerance, whereas transient overexpression enhanced it. Furthermore, the TAG content quantification indicated that CsDGAT1A and CsDGAT2D promoted TAG accumulation. In conclusion, this study elucidates the lipid metabolism mechanism in cucumber's low-temperature stress response and offers valuable insights for the cultivation of cold-tolerant cucumber plants.

Consequences of the deletion of the major specialized metabolite biosynthetic pathways of Streptomyces coelicolor on the metabolome and lipidome of this strain.

Chassis strains, derived from Streptomyces coelicolor M145, deleted for one or more of its four main specialized metabolites biosynthetic pathways (CPK, CDA, RED and ACT), in various combinations, were constructed for the heterologous expression of specialized metabolites biosynthetic pathways of various types and origins. To determine consequences of these deletions on the metabolism of the deleted strains comparative lipidomic and metabolomic analyses of these strains and of the original strain were carried out. These studies unexpectedly revealed that the deletion of the peptidic clusters, RED and/or CDA, in a strain deleted for the ACT cluster, resulted into a great increase in the triacylglycerol (TAG) content, whereas the deletion of polyketide clusters, ACT and CPK had no impact on TAG content. Low or high TAG content of the deleted strains was correlated with abundance or paucity in amino acids, respectively, reflecting high or low activity of oxidative metabolism. Hypotheses based on what is known on the bio-activity and the nature of the precursors of these specialized metabolites are proposed to explain the unexpected consequences of the deletion of these pathways on the metabolism of the bacteria and on the efficiency of the deleted strains as chassis strains.

Membranes that make fat: roles of membrane lipids as acyl donors for triglyceride synthesis and organelle function.

Triglycerides constitute an inert storage form for fatty acids deposited in lipid droplets and are mobilized to provide metabolic energy or membrane building blocks. The biosynthesis of triglycerides is highly conserved within eukaryotes and normally involves the sequential esterification of activated fatty acids with a glycerol backbone. Some eukaryotes, however, can also use cellular membrane lipids as direct fatty acid donors for triglyceride synthesis. The biological significance of a pathway that generates triglycerides at the expense of organelle membranes has remained elusive. Here we review current knowledge on how cells use membrane lipids as fatty acid donors for triglyceride synthesis and discuss the hypothesis that a primary function of this pathway is to regulate membrane lipid remodeling and organelle function.

Identification of triacylglycerol remodeling mechanism to synthesize unusual fatty acid containing oils.

Typical plant membranes and storage lipids are comprised of five common fatty acids yet over 450 unusual fatty acids accumulate in seed oils of various plant species. Plant oils are important human and animal nutrients, while some unusual fatty acids such as hydroxylated fatty acids (HFA) are used in the chemical industry (lubricants, paints, polymers, cosmetics, etc.). Most unusual fatty acids are extracted from non-agronomic crops leading to high production costs. Attempts to engineer HFA into crops are unsuccessful due to bottlenecks in the overlapping pathways of oil and membrane lipid synthesis where HFA are not compatible. Physaria fendleri naturally overcomes these bottlenecks through a triacylglycerol (TAG) remodeling mechanism where HFA are incorporated into TAG after initial synthesis. TAG remodeling involves a unique TAG lipase and two diacylglycerol acyltransferases (DGAT) that are selective for different stereochemical and acyl-containing species of diacylglycerol within a synthesis, partial degradation, and resynthesis cycle. The TAG lipase interacts with DGAT1, localizes to the endoplasmic reticulum (with the DGATs) and to puncta around the lipid droplet, likely forming a TAG remodeling metabolon near the lipid droplet-ER junction. Each characterized DGAT and TAG lipase can increase HFA accumulation in engineered seed oils.

HuR promotes triglyceride synthesis and intestinal fat absorption.

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

Bta-miR-200a Regulates Milk Fat Biosynthesis by Targeting IRS2 to Inhibit the PI3K/Akt Signal Pathway in Bovine Mammary Epithelial Cells.

Milk fat synthesis has garnered significant attention due to its influence on the quality of milk. Recently, an increasing amount of proofs have elucidated that microRNAs (miRNAs) are important post-transcriptional factor involved in regulating gene expression and play a significant role in milk fat synthesis. MiR-200a was differentially expressed in the mammary gland tissue of dairy cows during different lactation periods, which indicated that miR-200a was a candidate miRNA involved in regulating milk fat synthesis. In our research, we investigated the potential function of miR-200a in regulating milk fat biosynthesis in bovine mammary epithelial cells (BMECs). We discovered that miR-200a inhibited cellular triacylglycerol (TAG) synthesis and suppressed lipid droplet formation; at the same time, miR-200a overexpression suppressed the mRNA and protein expression of milk fat metabolism-related genes, such as fatty acid synthase (FASN), peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), CCAAT enhancer binding protein alpha (CEBPα), etc. However, knocking down miR-200a displayed the opposite results. We uncovered that insulin receptor substrate 2 (IRS2) was a candidate target gene of miR-200a through the bioinformatics online program TargetScan. Subsequently, it was confirmed that miR-200a directly targeted the 3'-untranslated region (3'-UTR) of IRS2 via real-time fluorescence quantitative PCR (RT-qPCR), western blot analysis, and dual-luciferase reporter gene assay. Additionally, IRS2 knockdown in BMECs has similar effects to miR-200a overexpression. Our research set up the mechanism by which miR-200a interacted with IRS2 and discovered that miR-200a targeted IRS2 and modulated the activity of the PI3K/Akt signaling pathway, thereby taking part in regulating milk fat synthesis in BMECs. Our research results provided valuable information on the molecular mechanisms for enhancing milk quality from the view of miRNA-mRNA regulatory networks.

Avaliação prospectiva das repercussões no perfil lipídico das cirurgias que envolvem lipoaspiração e dermolipectomias / Prospective assessment of the repercussions on the lipid profile of surgeries involving liposuction and dermolipectomies

Introdução: Lipoaspiração associada a dermolipectomias é o procedimento cirúrgico mais comumente realizado em cirurgia plástica. Apesar de ser considerada uma cirurgia extremamente segura, algumas considerações devem ser levantadas a respeito dos possíveis efeitos metabólicos que essas cirurgias possam causar. O desenvolvimento da técnica tumescente de lipoaspiração permitiu a remoção de grande quantidade de gordura de modo mais seguro. O objetivo é comparar as variações do perfil lipídico em pós-operatório precoce e tardio de pacientes submetidos à lipoaspiração e dermolipectomias. Métodos: Entre outubro de 2006 e junho de 2012, 40 pacientes do sexo feminino candidatas a cirurgias que envolviam lipoaspiração e dermolipectomias foram acompanhadas prospectivamente e o perfil lipídico foi analisado por meio de exames no pré-operatório e no pós-operatório. As cirurgias realizadas foram: mamoplastia + lipoaspiração, abdominoplastia + lipoaspiração e lipoabdominoplastia + mamoplastia. Resultados: Das 40 pacientes que foram acompanhadas no estudo, 20 pacientes do sexo feminino foram selecionadas (após a aplicação dos critérios de exclusão). Em consonância com nosso estudo, Cazes, em 1996, demonstrou que após 12 meses de pós-operatório de lipoabdominoplastia não houve alteração do perfil lipídico das pacientes. Conclusão: Após análise pré- e pós-operatória de 20 pacientes, observamos que não há alterações estatísticas significantes em relação ao perfil lipídico com tendência de equilíbrio das aferições em um ano em patamares próximos aos observados no pré-operatório.

Introduction: Liposuction associated with dermolipectomies is the most commonly performed surgical procedure in plastic surgery. Although regarded as an extremely safe surgery, some considerations must be taken on the possible metabolic effects of these surgeries. The development of the tumescent technique in liposuction allowed the safer removal of large amounts of fat. The objective is to compare lipid profile variations in the early and late postoperative period in patients undergoing liposuction and dermolipectomies. Methods: Between October 2006 and June 2012, 40 female patients who were candidates for surgeries involving liposuction and dermolipectomies were prospectively followed, and the lipid profile was analyzed through preoperative and postoperative examinations. The surgeries performed were mammoplasty + liposuction, abdominoplasty + liposuction, and lipoabdominoplasty + mammoplasty. Results: Of the 40 female patients who were followed, 20 were selected (after applying the exclusion criteria). In agreement with our study, in 1996, Cazes showed that there were no changes in the lipid profile of patients 12 months after lipoabdominoplasty. Conclusion: After a preoperative and postoperative analysis of 20 patients, it was observed that there were no statistically significant changes in the lipid profile and that the measurements after 1 year were close to those obtained in the preoperative period.

Efeito hepatoprotetor do consumo crônico de dieptanoína e trieptanoína contra a esteatose em ratos / Hepatoprotective effect of diheptanoin and tritreptanoin chronic consumption against steatosis in rats

OBJETIVO: Avaliar o efeito do consumo crônico de di e trieptanoínas sobre a esteatose hepática (EH) em ratos. METODOLOGIA: Ratos Wistar submetidos à dieta AIN-93 com 0 por cento, 30 por cento ou 50 por cento de substituição do óleo por óleo rico em di e trieptanoína, grupos TAGC(7)0, TAGC(7)30 e TAGC(7)50, respectivamente, por nove meses. O grupo-controle recebeu ração Labina®. Analisaram-se histologia e provas de função e lesão hepática, glicemia e perfil lipídico sérico. Realizaram-se análise de variância, teste F, teste de Dunnet e análises de regressão uni e multivariadas (p < 0,05). RESULTADOS: TAGC(7)0, TAGC(7)30 e TAGC(7)50 desenvolveram EH; 80 por cento de casos graves no TAGC(7)0 contra 40 por cento no TAGC(7)50. Os pesos absoluto (PAF) e relativo do fígado (PRF) foram maiores em TAGC(7)0 e TAGC(7)30 e a glicemia foi maior em TAGC(7)30 e TAGC(7)50, que no grupo-controle. Colesterol total, LDL-c, LDL-c/HDL-c e proteínas totais foram maiores no grupo-controle. O óleo experimental reduziu o PRF e determinou tendência de redução do peso corporal, PAF, percentual de lipídios hepáticos e graus de EH (GHE). As variáveis explicativas para GHE foram peso final, glicemia, albumina, HDL-c, LDL-c, LDL-c/HDL-c, VLDL-c e fosfatase alcalina. CONCLUSÕES: Sugere-se que di e trieptanoínas exerçam efeito hepatoprotetor contra a EH, em ratos, em uma feição dose-dependente.

OBJECTIVE: to evaluate the effect of chronic consumption of di- and triheptanoin on hepatic steatosis (HS) in rats. METHODOLOGY: Wistar rats were submitted to a diet AIN-93 with 0, 30 or 50 percent of its oil substituted with an oil rich in di- and triheptanoin, groups TAGC(7)0, TAGC(7)30 and TAGC(7)50 respectively, for nine months. The control group received Labina®. Liver histology, hepatic lesion and function proofs, glycemia and lipid profile, were performed. Variance analyses, F-test, Dunnet´s test and uni- and multivariate regression analyses were performed (p<0.05). RESULTS: TAGC(7)0, TAGC(7)30 and TAGC(7)50 developed HS; 80 percent of severe cases in TAGC(7)0, as against 40 percent in TAGC(7)50. The absolute (ALW) and relative (RLW) liver weights were higher in TAGC(7)0 and TAGC(7)30, and glycemia was greater in TAGC(7)30 and TAGC(7)50, than in the Control. Total cholesterol, LDL-c, LDL-c/HDL-c and total proteins were higher in the Control. The experimental oil reduced RLW and showed a tendency in the reduction of body weight, ALW, percentage of hepatic lipids and the severity of HS. The explanatory variables in relation to HS were final weight, glycemia, albumin, HDL-c, LDL-c, LDL-c/HDL-c, VLDL-c and alkaline phosphatase. CONCLUSIONS: It is suggested that di- and triheptanoin have a hepatoprotector effect against HS, in rats, in a dose-dependant manner.

Expresión intestinal de la apolipoproteína A-V: nuevas perspectivas en el conocimiento del metabolismo de los triglicéridos / Intestinal expression of apolipoprotein A-V: new perspectives in the knowledge of the triglyceride metabolism

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Acylglycerol synthesis in liver of type II diabetic rats fed a diet supplemented with either N-6 or N-3 fatty acids

Liver is one of the tissues most actively involved in triacylglycerol synthesis and secretion. Hypertriglyceridemia is commonly associated with the diabetic state which has been detected in very young rats after the induction of experimental diabetes. In the present work, acylglycerol synthesis in liver of streprozotocintreated rats, fed a diet supplemented with n-3 and n-6 fatty acids, was studied. At the onset of the experiment, plasma triacylglycerol levels increased significantly in diabetic animals when compared to controls. Two weeks after the dietary treatment, the aforementoined parameter decreased in diabetic animals consuming either n-6 or n-3 fatty acids. In control rats, n-3 fatty acids depressed triacyglycerol synthesis in liver microsomes. In the diabetic group both diets increased diacylglycerol and triacylglycerol synthesis. The addition on liver cytosolic fraction from control rats to the incubation medium, stimulated the triacylglycerol synthesis in all the groups. Nevertheless, the radioactivity recovered in the neutral lipid fractions was lower in the samples from rats fed n-3 fatty acids compared to n-6. We conclude that dietary n-3 fatty acids decreased significantly triacylglycerol plasma levels in diabetic rats probably through the inhibiton of liver triacylglycerol secretion. In addition, there probably is an n-3 fatty sensitive factor in the liver cytosolic fraction able to depress triglyceride synthesis.

The role of insulin in the control of hepatic fatty acid and glycerolipid metabolism assessed by studies in vivo

The liver secretes triacylglycerol-rich very-low-density lipoproteins (VLDL). Teleologically, it would be expected that during the prandial/early absorptive periodo the rate of hepatic VLDL secretion would be inhibited, in view of the concomitant secretation of chylomicrons from the gut. Such inhibition would limit the extent and duration of post-prandial hyperlipaemia. Experiments in wich the fatty acids of the liver were labelled specifically in rats in vivo show that, during a meal, triacylglycerol secretion was inhibited through a combination of diversion of flux towards phospholipid synthesis, and inhibition of the fractional rate of secretion of triacylglycerol. These adaptations occur even in diabetic rats, indicating that insulin is not obligatorily involved in mediating them. It is suggested that uptake of osmolytes (e.g. amino acids that are cotransported with Na+ions into hepatocytes) from the portal circulation may result in increased hepatocyte volume and that this, in turn, alters fatty acid and glycerolipid metabolism independently of, but possibly in synergy with, insulin action.