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.

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.

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.

A point mutation decouples the lipid transfer activities of microsomal triglyceride transfer protein.

Apolipoprotein B-containing lipoproteins (B-lps) are essential for the transport of hydrophobic dietary and endogenous lipids through the circulation in vertebrates. Zebrafish embryos produce large numbers of B-lps in the yolk syncytial layer (YSL) to move lipids from yolk to growing tissues. Disruptions in B-lp production perturb yolk morphology, readily allowing for visual identification of mutants with altered B-lp metabolism.

An HPLC-CAD/fluorescence lipidomics platform using fluorescent fatty acids as metabolic tracers.

Fluorescent lipids are important tools for live imaging in cell culture and animal models, yet their metabolism has not been well-characterized. Here we describe a novel combined HPLC and LC-MS/MS method developed to characterize both total lipid profiles and the products of fluorescently labeled lipids. Using this approach, we found that lipids labeled with the fluorescent tags, 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza--indacene (BODIPY FL), 4,4-difluoro-5-(2-thienyl)-4-bora-3a,4a-diaza--indacene [BODIPY(558/568)], and dipyrrometheneboron difluoride undecanoic acid (TopFluor) are all metabolized into varying arrays of polar and nonpolar fluorescent lipid products when they are fed to larval zebrafish.

TM6SF2 rs58542926 impacts lipid processing in liver and small intestine.

Unlabelled: The transmembrane 6 superfamily member 2 (TM6SF2) loss-of-function variant rs58542926 is a genetic risk factor for nonalcoholic fatty liver disease and progression to fibrosis but is paradoxically associated with lower levels of hepatically derived triglyceride-rich lipoproteins. TM6SF2 is expressed predominantly in liver and small intestine, sites for triglyceride-rich lipoprotein biogenesis and export. In light of this, we hypothesized that TM6SF2 may exhibit analogous effects on both liver and intestine lipid homeostasis.

Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses.

Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery.

Methods for Assessing Nuclear Rotation and Nuclear Positioning in Developing Skeletal Muscle Cells.

Skeletal muscle cells are large syncytia, containing hundreds of nuclei positioned regularly along the length of the fiber. During development, nuclei are actively distributed throughout the myotube by the microtubule motor proteins, kinesin-1, and cytoplasmic dynein. Nuclear movement consists of translocation along the long axis of the cell concurrent with three-dimensional rotation of nuclei.

Nesprins anchor kinesin-1 motors to the nucleus to drive nuclear distribution in muscle cells.

During skeletal muscle development, nuclei move dynamically through myotubes in a microtubule-dependent manner, driven by the microtubule motor protein kinesin-1. Loss of kinesin-1 leads to improperly positioned nuclei in culture and in vivo. Two models have been proposed to explain how kinesin-1 functions to move nuclei in myotubes.

Opposing microtubule motors drive robust nuclear dynamics in developing muscle cells.

Dynamic interactions with the cytoskeleton drive the movement and positioning of nuclei in many cell types. During muscle cell development, myoblasts fuse to form syncytial myofibers with nuclei positioned regularly along the length of the cell. Nuclear translocation in developing myotubes requires microtubules, but the mechanisms involved have not been elucidated.

Capzb2 interacts with beta-tubulin to regulate growth cone morphology and neurite outgrowth.

Capping protein (CP) is a heterodimer that regulates actin assembly by binding to the barbed end of F-actin. In cultured nonneuronal cells, each CP subunit plays a critical role in the organization and dynamics of lamellipodia and filopodia. Mutations in either alpha or beta CP subunit result in retinal degeneration in Drosophila.

Greater transport efficiencies of the membrane fatty acid transporters FAT/CD36 and FATP4 compared with FABPpm and FATP1 and differential effects on fatty acid esterification and oxidation in rat skeletal muscle.

In selected mammalian tissues, long chain fatty acid transporters (FABPpm, FAT/CD36, FATP1, and FATP4) are co-expressed. There is controversy as to whether they all function as membrane-bound transporters and whether they channel fatty acids to oxidation and/or esterification. Among skeletal muscles, the protein expression of FABPpm, FAT/CD36, and FATP4, but not FATP1, correlated highly with the capacities for oxidative metabolism (r>or=0.

Aged men experience disturbances in recovery following submaximal exercise.

Background: Physiological responses to exercise of moderate intensity and duration among aged compared to young adults have yet to be clearly defined. Further, the effects of aging on the rate and effectiveness of postexercise recovery are unknown.

Methods: Here, selected physiological responses during and following exercise of the same relative intensity were examined in untrained young and aged men.

The neuromuscular junction: anatomical features and adaptations to various forms of increased, or decreased neuromuscular activity.

The neuromuscular junction (NMJ) allows communication between motor neurons and muscle fibers. During development, marked morphological changes occur as the functional NMJ is formed. During the postnatal period of rapid growth and muscle enlargement, endplate size concurrently increases.

Neuromuscular adaptations to spaceflight are specific to postural muscles.

The effects of microgravity were determined in muscles of differing function and myofiber-type composition. Rats were assigned either to a 10-day spaceflight mission or to ground-based control conditions. Following the experimental period, hindlimb muscles were obtained from both groups.

Age-related differences in synaptic plasticity following muscle unloading.

The objective of the present investigation was to determine the effects of muscle unloading-a form of subtotal disuse- on the morphology of the neuromuscular junction (NMJ) in younger and aged animals. Sixteen aged (22 months) and 16 young adult (8 months) male Fischer 344 rats were assigned to control and hindlimb suspension (HS) conditions (n=8/group). At the conclusion of the 4 week experimental period, soleus muscles were collected, and immunofluorescent procedures were used to visualize acetylcholine (ACh) vesicles and receptors, nerve terminal branching, as well as NCAM and NT-4 expression.

Evaluation of cardiovascular demands of game play and practice in women's ice hockey.

Preparation for the physical demands of competition often involves game simulation during practice. This paradigm is thought to promote physiological adaptations that enhance maximal performance. However, a mismatch between practice intensity and actual competition intensity may not provide adequate training to achieve optimal game-play fitness.

Bronchoconstriction during cross-country skiing: is there really a refractory period?

Purpose: The asthmatic airway responds to exercise by bronchodilation (BD) during and bronchoconstriction (BC) after exercise. A refractory period induced by an initial exercise challenge that provides protection against BC during a subsequent exercise bout has also been observed. However, no studies examining during-exercise response or refractoriness during long-duration field exercise by elite athletes have been performed.