A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins.

Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined.

Zebrafish are resilient to the loss of major diacylglycerol acyltransferase enzymes.

In zebrafish, maternally deposited yolk is the source of nutrients for embryogenesis prior to digestive system maturation. Yolk nutrients are processed and secreted to the growing organism by an extra-embryonic tissue, the yolk syncytial layer (YSL). The export of lipids from the YSL occurs through the production of triacylglycerol-rich lipoproteins.

Directly Measuring Atherogenic Lipoprotein Kinetics in Zebrafish with the Photoconvertible LipoTimer Reporter.

Lipoprotein kinetics are a crucial factor in understanding lipoprotein metabolism since a prolonged time in circulation can contribute to the atherogenic character of apolipoprotein-B (ApoB)-containing lipoproteins (B-lps). Here, we report a method to directly measure lipoprotein kinetics in live developing animals. We developed a zebrafish geneticly encoded reporter, LipoTimer, in which endogenous ApoBb.

Growing Project BioEYES: A Reflection on 20 Years of Developing and Replicating a K-12 Science Outreach Program.

Project BioEYES celebrated 20 years in K12 schools during the 2022-2023 school year. Using live zebrafish () during week-long science experiments, sparks the interest of students and teachers from school districts, locally and globally. Over the past two decades, BioEYES has been replicated in different ways based on the interest and capacity of our partners.

Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look.

Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile.

Pla2g12b drives expansion of triglyceride-rich lipoproteins.

Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear.

Paraoxonase-like APMAP maintains endoplasmic reticulum-associated lipid and lipoprotein homeostasis.

Oxidative stress perturbs lipid homeostasis and contributes to metabolic diseases. Though ignored compared to mitochondrial oxidation, the endoplasmic reticulum (ER) generates reactive oxygen species requiring antioxidant quality control. Using multi-organismal profiling featuring , zebrafish, and mammalian cells, here we characterize the paraoxonase-like APMAP as an ER-localized protein that promotes redox and lipid homeostasis and lipoprotein maturation.

Bulky hydrophobic side chains in the β1-sandwich of microsomal triglyceride transfer protein are critical for the transfer of both triglycerides and phospholipids.

Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apolipoprotein B-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine.

Is It Ever Wise to Edit Wild-Type Alleles? Engineered CRISPR Alleles Versus Millions of Years of Human Evolution.

The tremendous burden of lipid metabolism diseases, coupled with recent developments in human somatic gene editing, has motivated researchers to propose population-wide somatic gene editing of PCSK9 (proprotein convertase subtilisin/kexin type 9) within the livers of otherwise healthy humans. The best-characterized molecular function of PCSK9 is its ability to regulate plasma LDL (low-density lipoprotein) levels through promoting LDL receptor degradation. Individuals with loss-of-function PCSK9 variants have lower levels of plasma LDL and reduced cardiovascular disease.

Fish Playpens - Method for raising individual juvenile zebrafish on a recirculating system for studies requiring repeated measures.

Even though many experimental approaches benefit from tracking individual larval animals, there is yet to be a commercial zebrafish rack system designed to accomplish this task. Thus, we invented playpens, an acrylic and screen container, to raise 12 individual zebrafish juveniles per standard 10 L tank on an existing recirculating fish system. During a week-long experiment, fish raised in playpens grow to the same size as conventionally raised juveniles.

Predictors of transportation-related barriers to healthcare access in a North American suburb.

Aim: To identify predictors of transportation-related barriers to healthcare access in a North American suburb.

Subject And Methods: Data from the 2022 Scarborough Survey were used, comprising n = 528 adults living in Scarborough, which is a subu View Article and Find Full Text PDF

Getting groceries during the pandemic: How transit remained important despite the rise of e-delivery.

Background: We model the use of public transit to reach grocery stores and the use of online delivery services to get groceries, before and during the COVID-19 pandemic among people who used transit regularly prior to the crisis.

Methods: We draw upon a panel survey of pre-pandemic transit riders in Vancouver and Toronto. We conduct multivariable two-step tobit regression models that predict the likelihood of a respondent using transit as their primary mode for getting groceries before the pandemic (step 1) and then during the pandemic (step 2).

From worms to humans: Understanding intestinal lipid metabolism via model organisms.

The intestine is responsible for efficient absorption and packaging of dietary lipids before they enter the circulatory system. This review provides a comprehensive overview of how intestinal enterocytes from diverse model organisms absorb dietary lipid and subsequently secrete the largest class of lipoproteins (chylomicrons) to meet the unique needs of each animal. We discuss the putative relationship between diet and metabolic disease progression, specifically Type 2 Diabetes Mellitus.

Facing the future of transit ridership: shifting attitudes towards public transit and auto ownership among transit riders during COVID-19.

Unlabelled: Public transit agencies face a transformed landscape of rider demand and political support as the COVID-19 pandemic recedes. We explore people's motivations for returning to or avoiding public transit a year into the pandemic. We draw on a March 2021 follow-up survey of over 1,900 people who rode transit regularly prior to the COVID-19 pandemic in Toronto and Vancouver, Canada, and who took part in a prior survey on the topic in May 2020.

Who's cooking tonight? A time-use study of coupled adults in Toronto, Canada.

Understanding how coupled adults arrange food-related labor in relation to their daily time allocation is of great importance because different arrangements may have implications for diet-related health and gender equity. Studies from the time-use perspective argue that daily activities such as work, caregiving, and non-food-related housework can potentially compete for time with foodwork. However, studies in this regard are mostly centered on individual-level analyses.

A missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish.

Hepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality.

Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding.

Background: The ability of animals and their microbiomes to adapt to starvation and then restore homeostasis after refeeding is fundamental to their continued survival and symbiosis. The intestine is the primary site of nutrient absorption and microbiome interaction, however our understanding of intestinal adaptations to starvation and refeeding remains limited. Here we used RNA sequencing and 16S rRNA gene sequencing to uncover changes in the intestinal transcriptome and microbiome of zebrafish subjected to long-term starvation and refeeding compared to continuously fed controls.

The uneven impacts of avoiding public transit on riders' access to healthcare during COVID-19.

Background: During the COVID-19 pandemic, many urban residents stopped riding public transit despite their reliance on it to reach essential services like healthcare. Few studies have examined the implications of public transit reliance on riders' ability to reach healthcare when transit is disrupted. To understand how shocks to transportation systems impact healthcare access, this study measures the impact of avoiding public transit on the ability of riders to access healthcare and pharmacy services during lockdowns.

Imaging cytoplasmic lipid droplets in vivo with fluorescent perilipin 2 and perilipin 3 knock-in zebrafish.

Cytoplasmic lipid droplets are highly dynamic storage organelles that are critical for cellular lipid homeostasis. While the molecular details of lipid droplet dynamics are a very active area of investigation, this work has been primarily performed in cultured cells. Taking advantage of the powerful transgenic and in vivo imaging opportunities available in zebrafish, we built a suite of tools to study lipid droplets in real time from the subcellular to the whole organism level.