Differential effects of natural palm oil, chemically and enzymatically-modified palm oil on weight gain, blood lipid metabolites and fat deposition in a pediatric pig model

Background: Increasing prevalence of obesity and overweight in the Western world, continue to be a major health threat and is responsible for increased health care costs. Dietary intervention studies show a strong positive association between saturated fat intake and the development of obesity and cardiovascular disease. This study investigated the effect of positional distribution of palmitic acid (Sn-1, 2 & 3) of palm oil on cardiovascular health and development of obesity, using weaner pigs as a model for young children.

Methods: Male and female weaner piglets were randomly allocated to 4 dietary treatment groups: 1) pork lard (LRD); 2) natural palm olein (NPO); 3) chemically inter-esterified PO (CPO) and 4) enzymatically inter-esterified PO (EnPO) as the fat source. Diets were formulated with 11% lard or with palm olein in order to provide 31% of digestible energy from fat in the diet and were balanced for cholesterol, protein and energy across treatments.

Results: From 8 weeks onwards, pigs on EnPO diet gained (P < 0.05) more weight than all other groups. Feed conversion efficiency (feed to gain) over the 12 week experimental period did not vary between treatment groups. Plasma LDL-C content and LDL-C/HDL-C ratio in pigs fed natural PO tended to be lower compared to all other diets. The natural PO lowered (P < 0.02) the plasma triglyceride (TG) content relative to the lard or EnPO diets, but was not different from the CPO diet. The natural PO diet was associated with lower (P < 0.05) saturated fat levels in subcutaneous adipose tissue than the CPO and EnPO diets that had lower saturated fat levels than the lard diet. Female pigs had lower lean and higher fat and fat:lean ratio in the body compared with male pigs. No difference in weight gain or blood lipid parameters was observed between sexes.

Conclusions: The observations on plasma TG, muscle and adipose tissue saturated fatty acid contents and back fat (subcutaneous) thickness suggest that natural palm oil may reduce deposition of body fat. In addition, dietary supplementation with natural palm oil containing palmitic acid at different positions in meat producing animals may lead to the production of meat and meat products with lower saturated fats. An increase in fat content and a decrease in lean content in female pigs resulted in an increased body fat:lean ratio but gender had no effect on blood lipid parameters or insulin concentrations.

Marine protected areas of the Otway bioregion

Along Victoria’s coastline there are 30 Marine Protected Areas (MPAs) that have been established to protect the state’s significant marine environmental and cultural values. These MPAs include 13 Marine National Parks (MNPs), 11 Marine Sanctuaries (MSs), 3 Marine and Coastal Parks, 2 Marine Parks, and a Marine Reserve, and together these account for 11.7% of the Victorian marine environment. The highly protected Marine National Park System, which is made up of the MNPs and MSs, covers 5.3% of Victorian waters and was proclaimed in November 2002. This system has been designed to be representative of the diversity of Victoria’s marine environment and aims to conserve and protect ecological processes, habitats, and associated flora and fauna. The Marine National Park System is spread across Victoria’s five marine bioregions with multiple MNPs and MSs in each bioregion, with the exception of Flinders bioregion which has one MNP. All MNPs and MSs are “no-take” areas and are managed under the National Parks Act (1975) - Schedules 7 and 8 respectively.

This report updates the first Marine Natural Values Study (Plummer et al. 2003) for the MPAs in the Otway bioregion on the west coast of Victoria and is one of a series of five reports covering Victoria’s Marine National Park System. It uses the numerous monitoring and research programs that have increased our knowledge since declaration and aims to give a comprehensive overview of the important natural values of each MNP and MS.

Marine protected areas of the central Victoria bioregion

Along Victoria’s coastline there are 30 Marine Protected Areas (MPAs) that have been established to protect the state’s significant marine environmental and cultural values. These MPAs include 13 Marine National Parks (MNPs), 11 Marine Sanctuaries (MSs), 3 Marine and Coastal Parks, 2 Marine Parks, and a Marine Reserve, and together these account for 11.7% of the Victorian marine environment. The highly protected Marine National Park System, which is made up of the MNPs and MSs, covers 5.3% of Victorian waters and was proclaimed in November 2002. This system has been designed to be representative of the diversity of Victoria’s marine environment and aims to conserve and protect ecological processes, habitats, and associated flora and fauna. The Marine National Park System is spread across Victoria’s five marine bioregions with multiple MNPs and MSs in each bioregion, with the exception of Flinders bioregion which has one MNP. All MNPs and MSs are “no-take” areas and are managed under the National Parks Act (1975) - Schedules 7 and 8 respectively.

This report updates the first Marine Natural Values Study (Plummer et al. 2003) for the MPAs in the Central Victoria bioregion on the central coast of Victoria and is one of a series of five reports covering Victoria’s Marine National Park System. It uses the numerous monitoring and research programs that have increased our knowledge since declaration and aims to give a comprehensive overview of the important natural values of each MNP and MS.

Marine protected areas of the Victorian embayments bioregion part 1 : Port Phillip Bay

Along Victoria’s coastline there are 30 Marine Protected Areas (MPAs) that have been established to protect the state’s significant marine environmental and cultural values. These MPAs include 13 Marine National Parks (MNPs), 11 Marine Sanctuaries (MSs), 3 Marine and Coastal Parks, 2 Marine Parks, and a Marine Reserve, and together these account for 11.7% of the Victorian marine environment. The highly protected Marine National Park System, which is made up of the MNPs and MSs, covers 5.3% of Victorian waters and was proclaimed in November 2002. This system has been designed to be representative of the diversity of Victoria’s marine environment and aims to conserve and protect ecological processes, habitats, and associated flora and fauna. The Marine National Park System is spread across Victoria’s five marine bioregions with multiple MNPs and MSs in each bioregion, with the exception of Flinders bioregion which has one MNP. All MNPs and MSs are “no-take” areas and are managed under the National Parks Act (1975) - Schedules 7 and 8 respectively.

This report updates the first Marine Natural Values Study (Plummer et al. 2003) for the MPAs in the Port Phillip Bay area of the Victorian Embayments bioregion and is one of a series of five reports covering Victoria’s Marine National Park System. It uses the numerous monitoring and research programs that have increased our knowledge since declaration and aims to give a comprehensive overview of the important natural values of each MNP and MS.

Marine protected areas of the Victorian embayments bioregion part 2 : Western Port Bay and Corner inlet

Along Victoria’s coastline there are 30 Marine Protected Areas (MPAs) that have been established to protect the state’s significant marine environmental and cultural values. These MPAs include 13 Marine National Parks (MNPs), 11 Marine Sanctuaries (MSs), 3 Marine and Coastal Parks, 2 Marine Parks, and a Marine Reserve, and together these account for 11.7% of the Victorian marine environment. The highly protected Marine National Park System, which is made up of the MNPs and MSs, covers 5.3% of Victorian waters and was proclaimed in November 2002. This system has been designed to be representative of the diversity of Victoria’s marine environment and aims to conserve and protect ecological processes, habitats, and associated flora and fauna. The Marine National Park System is spread across Victoria’s five marine bioregions with multiple MNPs and MSs in each bioregion, with the exception of Flinders bioregion which has one MNP. All MNPs and MSs are “no-take” areas and are managed under the National Parks Act (1975) - Schedules 7 and 8 respectively.

This report updates the first Marine Natural Values Study (Plummer et al. 2003) for the MNPs in the Western Port Bay (WP) and Corner Inlet (CI) areas of the Victorian Embayments bioregion. It covers Yaringa, French Island, Churchill Island and Corner Inlet MNPs. This report is one of a series of five reports covering Victoria’s Marine National Park System. It uses the numerous monitoring and research programs that have increased our knowledge since declaration and aims to give a comprehensive overview of the important natural values of each MNP.

Marine protected areas of the Flinders and Twofold Shelf bioregions

Along Victoria’s coastline there are 30 Marine Protected Areas (MPAs) that have been established to protect the state’s significant marine environmental and cultural values. These MPAs include 13 Marine National Parks (MNPs), 11 Marine Sanctuaries (MSs), 3 Marine and Coastal Parks, 2 Marine Parks, and a Marine Reserve, and together these account for 11.7% of the Victorian marine environment. The highly protected Marine National Park System, which is made up of the MNPs and MSs, covers 5.3% of Victorian waters and was proclaimed in November 2002. This system has been designed to be representative of the diversity of Victoria’s marine environment and aims to conserve and protect ecological processes, habitats, and associated flora and fauna. The Marine National Park System is spread across Victoria’s five marine bioregions with multiple MNPs and MSs in each bioregion, with the exception of Flinders bioregion which has one MNP. All MNPs and MSs are “no-take” areas and are managed under the National Parks Act (1975) - Schedules 7 and 8 respectively.

This report updates the first Marine Natural Values Study (Plummer et al. 2003) for the MPAs in the Flinders and Twofold Shelf bioregions on the east coast of Victoria and is one of a series of five reports covering Victoria’s Marine National Park System. It uses the numerous monitoring and research programs that have increased our knowledge since declaration and aims to give a comprehensive overview of the important natural values of each MNP and MS.

Metal and metalloid containing natural products and a brief overview of their applications in biology, biotechnology and biomedicine

Bioinorganic natural product chemistry is a relatively unexplored but rapidly developing field with enormous potential for applications in biology, biotechnology (especially in regards to nanomaterial development, synthesis and environmental cleanup) and biomedicine. In this review the occurrence of metals and metalloids in natural products and their synthetic derivatives are reviewed. A broad overview of the area is provided followed by a discussion on the more common metals and metalloids found in natural sources, and an overview of the requirements for future research. Special attention is given to metal hyperaccumulating plants and their use in chemical synthesis and bioremediation, as well as the potential uses of metals and metalloids as therapeutic agents. The potential future applications and development in the field are also discussed.

Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development

Human contains 49 ATP-binding cassette (ABC) transporter genes and the multidrug resistance associated proteins (MRP1/ABCC1, MRP2/ABCC2, MRP3/ABCC3, MRP4/ABCC4, MRP5/ABCC5, MRP6/ABCC6, MRP7/ABCC10, MRP8/ABCC11 and MRP9/ABCC12) belong to the ABCC family which contains 13 members. ABCC7 is cystic fibrosis transmembrane conductance regulator; ABCC8 and ABCC9 are the sulfonylurea receptors which constitute the ATP-sensing subunits of a complex potassium channel. MRP10/ABCC13 is clearly a pseudo-gene which encodes a truncated protein that is highly expressed in fetal human liver with the highest similarity to MRP2/ABCC2 but without transporting activity. These transporters are localized to the apical and/or basolateral membrane of the hepatocytes, enterocytes, renal proximal tubule cells and endothelial cells of the blood-brain barrier. MRP/ABCC members transport a structurally diverse array of important endogenous substances and xenobiotics and their metabolites (in particular conjugates) with different substrate specificity and transport kinetics. The human MRP/ABCC transporters except MRP9/ABCC12 are all able to transport organic anions, such as drugs conjugated to glutathione, sulphate or glucuronate. In addition, selected MRP/ABCC members may transport a variety of endogenous compounds, such as leukotriene C(4) (LTC(4) by MRP1/ABCC1), bilirubin glucuronides (MRP2/ABCC2, and MRP3/ABCC3), prostaglandins E1 and E2 (MRP4/ABCC4), cGMP (MRP4/ABCC4, MRP5/ABCC5, and MRP8/ABCC11), and several glucuronosyl-, or sulfatidyl steroids. In vitro, the MRP/ABCC transporters can collectively confer resistance to natural product anticancer drugs and their conjugated metabolites, platinum compounds, folate antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial oxyanions, peptide-based agents, and in concert with alterations in phase II conjugating or biosynthetic enzymes, classical alkylating agents, alkylating agents. Several MRP/ABCC members (MRPs 1-3) are associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. Drug targeting of these transporters to overcome MRP/ABCC-mediated multidrug resistance may play a role in cancer chemotherapy. Most MRP/ABCC transporters are subject to inhibition by a variety of compounds. Based on currently available preclinical and limited clinical data, it can be expected that modulation of MRP members may represent a useful approach in the management of anticancer and antimicrobial drug resistance and possibly of inflammatory diseases and other diseases. A better understanding of their substrates and inhibitors has important implications in development of drugs for treatment of cancer and inflammation.

Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)

Multidrug ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) play an important role in the extrusion of drugs from the cell and their overexpression can be a cause of failure of anticancer and antimicrobial chemotherapy. Recently, the mouse P-gp/Abcb1a structure has been determined and this has significantly enhanced our understanding of the structure-activity relationship (SAR) of mammalian ABC transporters. This paper highlights our current knowledge on the structural and functional properties and the SAR of human MRP1/ABCC1. Although the crystal structure of MRP1/ABCC1 has yet to be resolved, the current topological model of MRP1/ABCC1 contains two transmembrane domains (TMD1 and TMD2) each followed by a nucleotide binding domain (NBD) plus a third NH2-terminal TMD0. MRP1/ABCC1 is expressed in the liver, kidney, intestine, brain and other tissues. MRP1/ABCC1 transports a structurally diverse array of important endogenous substances (e.g. leukotrienes and estrogen conjugates) and xenobiotics and their metabolites, including various conjugates, anticancer drugs, heavy metals, organic anions and lipids. Cells that highly express MRP1/ABCC1 confer resistance to a variety of natural product anticancer drugs such as vinca alkaloids (e.g. vincristine), anthracyclines (e.g. etoposide) and epipodophyllotoxins (e.g. doxorubicin and mitoxantrone). MRP1/ABCC1 is associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. However, most compounds that efficiently reverse P-gp/ABCB1-mediated multidrug resistance have only low affinity for MRP1/ABCC1 and there are only a few effective and relatively specific MRP1/ABCC1 inhibitors available. A number of site-directed mutagenesis studies, biophysical and photolabeling studies, SAR and QSAR, molecular docking and homology modeling studies have documented the role of multiple residues in determining the substrate specificity and inhibitor selectivity of MRP1/ABCC1. Most of these residues are located in the TMs of TMD1 and TMD2, in particular TMs 4, 6, 7, 8, 10, 11, 14, 16, and 17, or in close proximity to the membrane/cytosol interface of MRP1/ABCC1. The exact transporting mechanism of MRP1/ABCC1 is unclear. MRP1/ABCC1 and other multidrug transporters are front-line mediators of drug resistance in cancers and represent important therapeutic targets in future chemotherapy. The crystal structure of human MRP1/ABCC1 is expected to be resolved in the near future and this will provide an insight into the SAR of MRP1/ABCC1 and allow for rational design of anticancer drugs and potent and selective MRP1/ABCC1 inhibitors.

Role of multidrug resistance associated proteins in drug development

The Multidrug Resistance Associated Proteins (MRPI, MRP2, MRP3, MRp4, MRp5, MRP6, MRP7, MRPS and MRP9) belong to the ATP-binding cassette superfamily (ABCC family) of transporters expressed differentially in the liver, kidney, intestine and blood-brain barrier. MRps transport a structurally diverse array of endo- and xenobiotics and their metabolites (in particular conjugates) and are subject to induction and inhibition by a variety of compounds. An increased efflux of natural product anticancer drugs and other anticancer agents by MRPs in cancer cells is associated with tumor resistance. These transporting proteins play a role in the absorption, distribution and elimination of various compounds in the body. There are increased reports on the clinical impact of genetic mutations of genes encoding MRP1-9. Therefore, MRPs have an important role in drug development, since a better understanding of their function and regulating mechanism can help minimize and avoid drug toxicity, unfavorable drug-drug interactions, and to overcome drug resistance.

Improving peak shapes with counter gradients in two-dimensional high performance liquid chromatography

To achieve the greatest peak capacity in two-dimensional high performance liquid chromatography (2D-HPLC) a gradient should be operated in both separation dimensions. However, it is known that when an injection solvent that is stronger than the initial mobile phase composition is deleterious to peak performance, thus causing problems when cutting a portion from one gradient into another. This was overcome when coupling hydrophilic interaction with reversed phase chromatography by introducing a counter gradient that changed the solvent strength of the second dimension injection. It was found that an injection solvent composition of 20% acetonitrile in water gave acceptable results in one-dimensional simulations with an initial composition of 5% acetonitrile. When this was transferred to a 2D-HPLC separation of standards it was found that a marked improvement in peak shape was gained for the moderately retained analytes (phenol and dimethyl phthalate), some improvement for the weakly retained caffeine and very little change for the strongly retained n-propylbenzene and anthracene which already displayed good chromatographic profiles. This effect was transferred when applied to a 2D-HPLC separation of a coffee extract where the indecipherable retention profile was transformed to a successful application multidimensional chromatography with peaks occupying 71% of the separation space according to the geometric approach to factor analysis.

The use of metabolomics in the study of metals in biological systems

Metabolomics may be defined as the comprehensive quantitative and/or qualitative analysis of all metabolites present in a bio-fluid, cell, tissue, or organism. It is essentially the study of biochemical phenotypes (or metabotypes). Metabolic profiles are context dependent, and vary in response to a variety of factors including environment and environmental stimuli, health status, disease and a myriad of other factors; as such, metabolomics has been applied to a wide range of fields and has been increasingly utilised to the study of the roles played by metals in a range of biological systems as well as, encouragingly, in understanding the underlying biochemical mechanisms. The role of metals (and metalloids) in biological organisms is complex and the majority of studies in this area have been performed in plants but the fields of natural product chemistry, human health and even bacterial corrosion of water distribution systems have been investigated using this technique. In this review some of the novel approaches in which the metabolomics toolbox has been used to unravel the roles of metals and metalloids in a range of biological systems are discussed and suggestions made for future research.

Multi-dimensional liquid chromatography and metabolomics, are two dimensions better than one?

 While data processing methods in metabolomic studies often work with 'n' number of dimensions, analytical techniques, with the notable exception of NMR, have mostly stuck only to one. Peak overlap continues to be a problem and there is an ever-present demand to maximize the number of metabolites that can be separated and identified in a single run. One method that might help to overcome these issues is multidimensional liquid chromatography, which uses two columns of different phases. A sequential collection of aliquots is made from the first column and reinjected onto a second, and the resulting data are then plotted in 2D or 3D space. The total peak capacity of such a system is the combined peak capacities of each column. The 'offline' version of this technique, using a fraction collector, was introduced over 30 years ago but with recent advances in instrumentation and software, particularly the 'online' approach using automated switching valves, has led to increasing interest in the technique. Both offline and online methods can be carried out as a comprehensive procedure, or via 'heart-cutting', in which only specific peaks are analysed in the second dimension. Past applications include proteomics, natural product chemistry, forensic science and pharmaceutical analysis. These successes are likely to be built on in the future as new column chemistries and bio-informatic approaches are developed. In this review an overview of the theory of twodimensional liquid chromatography is presented, its potential in the field of metabolomics is assessed and predictions for future research directions are made.