Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.

Nora Linscheid
Apr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878
Research

Members Event

Event participants

Carien du Plessis, Journalist; Co-Author, Understanding South Africa

James Hamill, Associate Fellow, International Institute for Strategic Studies; Author, Africa's Lost Leader: South Africa's Continental Role Since Apartheid

Martin Plaut, Senior Researcher, Institute of Commonwealth Studies; Co-Author, Understanding South Africa

Chair: Pumela Salela, UK Country Head, Brand South Africa 

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.

Genetic and genomic research has greatly advanced our understanding of heart disease. Yet, comprehensive, in-depth, quantitative maps of protein expression in hearts of living humans are still lacking. Using samples obtained during valve replacement surgery in patients with mitral valve prolapse (MVP), we set out to define inter-chamber differences, the intersect of proteomic data with genetic or genomic datasets, and the impact of left atrial dilation on the proteome of patients with no history of atrial fibrillation (AF).  We collected biopsies from right atria (RA), left atria (LA) and left ventricle (LV) of seven male patients with mitral valve regurgitation with dilated LA but no history of AF. Biopsy samples were analyzed by high-resolution mass spectrometry (MS), where peptides were pre-fractionated by reverse phase high-pressure liquid chromatography prior to MS measurement on a Q-Exactive-HF Orbitrap instrument. We identified 7,314 proteins based on 130,728 peptides. Results were confirmed in an independent set of biopsies collected from three additional individuals. Comparative analysis against data from post-mortem samples showed enhanced quantitative power and confidence level in samples collected from living hearts. Our analysis, combined with data from genome wide association studies suggested candidate gene associations to MVP, identified higher abundance in ventricle for proteins associated with cardiomyopathies and revealed the dilated LA proteome, demonstrating differential representation of molecules previously associated with AF, in non-AF hearts. This is the largest dataset of cardiac protein expression from human samples collected in vivo. It provides a comprehensive resource that allows insight into molecular fingerprints of MVP and facilitates novel inferences between genomic data and disease mechanisms. We propose that over-representation of proteins in ventricle is consequent not to redundancy but to functional need, and conclude that changes in abundance of proteins known to associate with AF are not sufficient for arrhythmogenesis.

Discussion at this event focused on findings from MPI's report examining the interior immigration enforcement system in the United States, including ICE data on deportations and arrests, and the responses of state and local governments, civil society, and consulates.  

Marking the release of an MPI study, this discussion examines the operation of today’s interior enforcement system and how state and local governments, civil society, and consulates are responding.    

The Houston metro area, home to 1.6 million immigrants, is diverse and rapidly growing. This report sketches the area's immigrant population, examining top origin countries, key socioeconomic measures, and more. It also explores how Hurricane Harvey affected the immigrant population, and how national policy changes under the Trump administration are being felt locally, including by DACA recipients and asylum seekers.

Experts share how states have approached Every Student Succeeds Act (ESSA) implementation, and areas where the law and state efforts to support English Learners can be improved.

All 50 states, the District of Columbia, and Puerto Rico have developed blueprints to meet their commitments under the Every Student Succeeds Act—including requirements that aim to raise the profile of English Learners (EL) in state accountability systems. This report breaks these plans down, comparing the significant diversity of approaches taken on everything from EL identification to tracking academic achievement.

Experts share how states have approached Every Student Succeeds Act (ESSA) implementation, areas where the law and state efforts to support English Learners can be improved, and findings from the compendium, The Patchy Landscape of State English Learner Policies under ESSA. 

Pentecostalism -- History -- 21st century.

Architecture -- Australia -- History -- 20th century.

A state law aimed at encouraging—or prodding—small, rural districts to merge has hit some speed bumps on the road to implementation.

An important problem in the field of Topological Data Analysis is defining topological summaries which can be combined with traditional data analytic tools. In recent work Bubenik introduced the persistence landscape, a stable representation of persistence diagrams amenable to statistical analysis and machine learning tools. In this paper we generalise the persistence landscape to multiparameter persistence modules providing a stable representation of the rank invariant. We show that multiparameter landscapes are stable with respect to the interleaving distance and persistence weighted Wasserstein distance, and that the collection of multiparameter landscapes faithfully represents the rank invariant. Finally we provide example calculations and statistical tests to demonstrate a range of potential applications and how one can interpret the landscapes associated to a multiparameter module.

The terraced hills of the Andes, the rice paddies of southern China, the oasis systems of the Maghreb: agriculture molds landscapes and places. Agriculture also shapes livelihoods, lifestyles, food traditions and cultures. What kind of plants grow or can’t grow, how they are harvested and what people eat define people’s lives.  Because our natural resources are under great strain, we need [...]

Zanu PF's limited commitment to the Global Political Agreement (GPA) and the resultant institutionalisation of the Government of National Unity (GNU) is why the party began to push for elections as from 2010, a strategy seen as steering the total collapse of the agreement.

IT is a truth universally acknowledged – at least by its advocates – that all things inexorably advance the cause of independence.

Tax-credit scholarship programs in 17 states collected $1.1 billion in contributions in 2017, a new analysis from the GAO finds.

In India, however, this is not likely to be a separate offering — Disney titles are being made available on the homegrown Hotstar, with no change in subscription plans, as of now.

The loan moratorium, as suggested by the Reserve Bank of India (RBI) last month and subsequently implemented by various lenders across the country, might be able to provide some temporary relief for now but could also play a hand in changing the credit landscape of the banking sector.

The Report Bosnia and Herzegovina Power Market Outlook to 2030 - Market Trends, Regulation and Competitive Landscape provides information on pricing, market analysis, shares, forecast, and company profiles for key industry participants. - MarketResearchReports.biz

As many Australian clients know, India announced a 21-day lockdown across the entire country, commencing on March 24. At this point, this is the largest lockdown in the world affecting more than a billion people. On April 14, this lockdown was extended until May 3.

Armed with drones, helicopters and military-grade software, a British photographer has developed a new way to remember glaciers

To find subjects to photograph, Kacper Kowalski takes to the air in a paramotor or gyrocopter, barely steering to allow the wind to dictate the direction

Much like other areas of cybercrime, attackers only refine and grow their skillset for infecting ATM systems from year-to-year. So what does the ATM landscape look like as of 2020? Let’s take a look.

Triple-negative breast cancer (TNBC) accounts for 10 to 20% of breast cancer, with chemotherapy as its mainstay of treatment due to lack of well-defined targets, and recent genomic sequencing studies have revealed a paucity of TNBC-specific mutations. Recurrent gene fusions comprise a class of viable genetic targets in solid tumors;...

Laterites preserved on both sides of the Western Ghats Escarpment of Peninsular India have formed by long-term lateritic weathering essentially after India–Seychelles continental break-up following Deccan Traps emplacement (c. 63 myr ago). Supergene manganese ores of the Western Ghats were formed on Late Archean manganese protores. Among Mn oxides composing the ores, cryptomelane (K-rich Mn oxide) was characterized and dated by ⁴⁰Ar/³⁹Ar geochronology. Measured ages complement those previously obtained in other South Indian manganese ores from the hinterland plateau and further document three major weathering periods, c. 53–44, c. 39–22 and c. 14–10 Ma, the last being documented for the first time in India. These periods coincide with global palaeoclimatic proxies and date the lateritic weathering of three successive palaeolandscapes of the Western Ghats that evolved under slow denudation (c. 8 m Ma^–1) over the last 44 myr and were mostly incised during the Neogene (<22 Ma). This indicates that the Western Ghats are a relict of a South Indian plateau preserved at the headwaters of very long east-flowing river systems and above the Western Ghats Escarpment. Topography and denudation history of this landscape do not require Neogene tilt of the Peninsula as recently proposed.

Supplementary material: Full details of field and sample description, methods and analytical data including electron probe microanalyses of cryptomelane, and isotopic analyses and degassing spectra of irradiated cryptomelane grains are available at https://doi.org/10.6084/m9.figshare.c.4726661

ABSTRACTThe Standard Days Method (SDM), a modern fertility awareness-based family planning method, has been introduced in 30 countries since its development in 2001. It is still unclear to what extent the SDM was mainstreamed within the family planning method mix, particularly in low- and middle-income country (LMIC) settings, where the SDM had been introduced by donors and implementing partners. This review of implementation science publications on the SDM in LMICs first looked at community pilot studies of the SDM to determine the acceptability of the method; correct use and efficacy rates; demographics of users; and changes to contraceptive prevalence rates and family planning behaviors, especially among men and couples. Then, we examined the status of the SDM in the 16 countries that had attempted to scale up the method within national family planning protocols, training, and service delivery. At the community level, evidence demonstrated a high level of acceptability of the method; efficacy rates comparable to the initial clinical trials; diversity in demographic characteristics of users, including first-time or recently discontinued users of family planning; increased male engagement in family planning; and improved couple's communication. Nationally, few countries had scaled up the SDM due to uneven stakeholder engagement, lackluster political will, and competing resource priorities. Results of this review could help policy makers determine the added value of the SDM in the contraceptive method mix and identify potential barriers to its implementation moving forward.

Certain habitats can help dampen the spread of ash dieback, which threatens ash trees.

The coronavirus shutdown has already had a big impact on the AFL — but could the effects spill over into the way the game is played in future?

The Department announced a settlement agreement with ValleyCrest Landscape Companies to resolve charges of hiring discrimination against U.S. citizens and other work-authorized domestic workers at its Virginia locations.

Playful Learning Landscapes lies at the intersection of developmental science and transformative placemaking to help urban leaders and practitioners advance and scale evidence-based approaches to create vibrant public spaces that promote learning and generate a sense of community ownership and pride. On Wednesday, February 26, the Center for Universal Education and the Bass Center for…

The novel coronavirus pandemic will shape the politics and economics of the Middle East in both the immediate and long term. As the pandemic’s repercussions will be felt far beyond public health, many of the dynamics that were set in motion before this crisis will be accelerated by its onset. While Israel closely watches the…

Playful Learning Landscapes lies at the intersection of developmental science and transformative placemaking to help urban leaders and practitioners advance and scale evidence-based approaches to create vibrant public spaces that promote learning and generate a sense of community ownership and pride. On Wednesday, February 26, the Center for Universal Education and the Bass Center for…

On May 1, the Center on the United States and Europe at Brookings hosted the 10th annual Sakıp Sabancı lecture featuring former Secretary of State Madeleine Albright. In her remarks, Secretary Albright offered perspectives on Turkey’s political and economic development during a period of rapid global transformation. She also explored how Turkey’s evolution is shaping its partnership with…