Publications by authors named "Victor A Zammit"

Although many studies have examined the biochemical metabolic pathways by which an egg (egg yolk) lowers blood lipid levels, data on the molecular biological mechanisms that regulate and induce the partitioning of hepatic glycerolipids are missing. The aim of this study was to investigate in vivo monitoring in four study groups using an animal nutrition biomodel fitted with a jugular-vein cannula after egg yolk intake: CON (control group, oral administration of 1.0 g of saline), T1 (oral administration of 1.

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The roles of DGAT1 and DGAT2 in lipid metabolism and insulin responsiveness of human skeletal muscle were studied using cryosections and myotubes prepared from muscle biopsies from control, athlete, and impaired glucose regulation (IGR) cohorts of men. The previously observed increases in intramuscular triacylglycerol (IMTG) in athletes and IGR were shown to be related to an increase in lipid droplet (LD) area in type I fibers in athletes but, conversely, in type II fibers in IGR subjects. Specific inhibition of both diacylglycerol acyltransferase (DGAT) 1 and 2 decreased fatty acid (FA) uptake by myotubes, whereas only DGAT2 inhibition also decreased fatty acid oxidation.

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Recently, applied technology in the form of the combination of a probiotics and a digital poultry system, with the convergence of Information and Communications Technology and farm animals, has enabled a new strategy to overcome the livestock production crisis caused by climate change, while maintaining sustainable poultry farming in terms of care, feeding, and environmental management systems for poultry. The aim of this study was to investigate the biological mechanisms of animal behavioral welfare and production improvement using the combination of a probiotics and a digital poultry system in broiler chickens. A total of 400 one-day-old male broilers (ROSS 308) were randomly divided into four treatment groups, with five replicates each (20 birds/replicate pen) in a completely randomized design: control group with a conventional poultry system without probiotics (CON), conventional poultry system with 500 ppm of probiotics (CON500), digital poultry control system without probiotics (DPCS), and digital poultry system with 500 ppm of probiotics (DPS500).

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The n-6/n-3 metabolic pathway associated with hepatic glycerolipid portioning plays a key role in preventing obesity. In this nutrition metabolism study, we used in vivo monitoring techniques with 40 obese male Sprague-Dawley strain rats attached with jugular-vein cannula after obesity was induced by a high-fat diet to determine the molecular mechanism associated with hepatic glycerolipid partitioning involving the n-6/n-3 metabolic pathway. Rats were randomly assigned to four groups (10 animals per group), including one control group (CON, n-6/n-3 of 71:1) and three treatment groups (n-6/n-3 of 4:1, 15:1 and 30:1).

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Diacylglycerol acyltransferases (DGAT) 1 and 2 catalyse the final step in triacylglycerol (TAG) synthesis, the esterification of fatty acyl-CoA to diacylglycerol. Despite catalysing the same reaction and being present in the same cell types, they exhibit different functions on lipid metabolism in various tissues. Yet, their roles in skeletal muscle remain poorly defined.

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The metabolic distribution via blood from liver of glycerolipids by omega-6 to omega-3 fatty acid ( -6    -3) ratio in monogastric animal nutrition is very important. In vivo monitoring technique using jugular-vein-cannulated rats as a nutritional model for monogastric animal can yield important insights into animal nutrition. This study was conducted to determine the effect of different -6    -3 ratios ( , , , ) on metabolic distribution of glycerolipids newly synthesized and secreted in the liver of the rats and explore the mechanism involved.

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We investigated whether, in view of its activity being expressed on both aspects of the endoplasmic reticulum (ER; dual membrane topology), diacylglycerol acyltransferase 1 (DGAT1) plays a distinctive role in determining the triglyceride (TAG) content of VLDL particles secreted by the liver. Mice in which the DGAT1 gene was specifically ablated in hepatocytes (DGAT1-LKO mice) had the same number of VLDL particles (apoB concentration) in the plasma 1 h after Triton 1339 treatment, but these particles were approximately half the size of VLDL particles secreted by control mice and had a proportionately decreased content of TAG, with normal cholesterol and cholesteryl ester contents. Analyses of purified microsomal fractions prepared from 16 h fasted control and DAGT1-LKO mice showed that the TAG/protein ratio in the ER was significantly lower in the latter.

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High stocking density (HSD) and heat stress (HS) caused by climate change can lower blood homeostasis and negatively impact the behavioral traits of animals. The objective of this study was to explore the influence of stocking densities on behavioral traits, blood parameters, immune responses, and stress hormones in meat ducks (Cherry valley, ) exposed to HS. A total of 320 meat ducks were assigned to four groups with different stocking densities using a randomized complete block design.

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Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency () protects against high fat diet-induced adipose tissue macrophage accumulation.

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Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogenesis. Adrenergic stimulation markedly increases glucose uptake, de novo lipogenesis, and FA oxidation simultaneously. The mechanism that enables this concerted response has hitherto been unknown.

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Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex. By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan. Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration.

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lThe liver regulates both glycaemia and triglyceridaemia. Hyperglycaemia and hypertriglyceridaemia are both characteristic of (pre)diabetes. Recent observations on the specialised role of DGAT2 (diacylglycerol acyltransferase 2) in catalysing the de novo synthesis of triacylglycerols from newly synthesized fatty acids and nascent diacylglycerols identifies this enzyme as the link between the two.

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The two diacylglycerol acyltransferases, DGAT1 and DGAT2, are known to have non-redundant functions, in spite of catalysing the same reaction and being present in the same cell types. The basis for this distinctiveness, which is reflected in the very different phenotypes of Dgat1(-/-) and Dgat2(-/-) mice, has not been resolved. Using selective inhibitors of human DGAT1 and DGAT2 on HepG2 cells and gene silencing, we show that, although DGAT2 activity accounts for a modest fraction (< 20%) of overall cellular DGAT activity, inhibition of DGAT2 activity specifically inhibits (and is rate-limiting for) the incorporation of de novo synthesized fatty acids and of glycerol into cellular and secreted triglyceride to a much greater extent than it affects the incorporation of exogenously added oleate.

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The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid β-oxidation in mammalian tissues. It is inhibited by malonyl-CoA, the first intermediate of fatty acid synthesis, and it responds to OMM curvature and lipid characteristics, which reflect long term nutrient/hormone availability. Here, we show that the N-terminal regulatory domain (N) of CPT1A can adopt two complex amphiphilic structural states, termed Nα and Nβ, that interchange in a switch-like manner in response to offered binding surface curvature.

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The purpose of this study was to investigate the sequence-dependence of oligomerization of transmembrane domain 2 (TM2) of rat carnitine palmitoyltransferase 1A (rCPT1A), to elucidate the role of this domain in the function of the full-length enzyme. Oligomerization of TM2 was studied qualitatively using complementary genetic assays that facilitate measurement of helix-helix interactions in the Escherichia coli inner membrane, and multiple quantitative biophysical methods. The effects of TM2-mutations on oligomerization and malonyl-CoA inhibition of the full-length enzyme (expressed in the yeast Pichia pastoris) were quantified.

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Triacylglycerol (TAG) synthesis and secretion are important functions of the liver that have major impacts on health, as overaccumulation of TAG within the liver (steatosis) or hypersecretion of TAG within very low density lipoproteins (VLDL) both have deleterious metabolic consequences. Two diacylglycerol acyltransferases (DGATs 1 and 2) can catalyze the final step in the synthesis of TAG from diacylglycerol, which has been suggested to play an important role in the transfer of the glyceride moiety across the endoplasmic reticular membrane for (re)synthesis of TAG on the lumenal aspect of the endoplasmic reticular (ER) membrane (Owen, M., Corstorphine, C.

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Daughters of diabetes patients have lower insulin sensitivity than women with no diabetes family history, but increase insulin sensitivity to a greater extent with exercise training. This study aimed to determine whether differences in circulating concentrations of adiponectin and leptin, and adipose tissue expression of their genes and receptors played a role. Women offspring of patients with type 2 diabetes mellitus (n = 34; age, 35.

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Article Synopsis
  • Pre-diabetes is linked to high blood sugar and lipid levels, increasing the risk of heart disease and issues with blood vessel function.
  • The study investigates how high glucose and fatty acid levels affect angiopoietin-1 (Ang1) signaling in heart microvascular cells, finding that high glucose significantly reduces Ang1's ability to activate a key receptor (Tie2) without impacting its expression.
  • They discovered that palmitic acid also inhibits Ang1's signaling but acts downstream of the receptor, indicating that both high glucose and fatty acids can disrupt the protective role of Ang1 and lead to vascular problems.
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Carnitine is important for cell function and survival primarily because of its involvement in the multiple equilibria between acylcarnitine and acyl-CoA esters established through the enzymatic activities of the family of carnitine acyltransferases. These have different acyl chain-length specificities and intracellular compartment distributions, and act in synchrony to regulate multiple aspects of metabolism, ranging from fuel-selection and -sensing, to the modulation of the signal transduction mechanisms involved in many homeostatic systems. This review aims to rationalise the extensive range of experimental and clinical data that have been obtained through the pharmacological use of L-carnitine and its short-chain acylesters, over the past two decades, in terms of the basic biochemical mechanisms involved in the effects of carnitine on the various cellular acyl-CoA pools in health and disease.

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Carnitine palmitoyltransferase 1 (CPT1) controls the rate of entry of long-chain fatty acids into the mitochondrial matrix for beta-oxidation and has been reported to exist as an oligomer. We have investigated the in vivo oligomerization of full-length rat CPT1A (rCPT1A) along with those of the N-terminal truncation/deletion mutants Delta(1-82), Delta(1-18), and Delta(19-30) expressed in yeast mitochondria. The data indicate that in liver mitochondria in vivo CPT1A exists as a hexamer but that during preparation and storage of mitochondria the order of oligomerization is rapidly reduced to the trimer, such that a mixture of hexamer and trimer is observed in isolated mitochondria in vitro.

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Triglyceride (TG) synthesis occurs in many cell-types, but only the adipocyte is specialised for TG storage. The increased incidence of obesity and its attendant pathologies have increased interest in pharmacological strategies aimed at inhibition of triglyceride synthesis. In the liver this would also appear to offer the advantages of the prevention of steatosis and/or dyslipidaemia.

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