Whole-body galactose oxidation as a robust functional assay to assess the efficacy of gene-based therapies in a mouse model of Galactosemia.

Despite the implementation of lifesaving newborn screening programs and a galactose-restricted diet, many patients with classic galactosemia develop long-term debilitating neurological deficits and primary ovarian insufficiency. Previously, we showed that the administration of human mRNA predominantly expressed in the gene-trapped mouse liver augmented the expression of hepatic GALT activity, which decreased not only galactose-1 phosphate (gal-1P) in the liver but also peripheral tissues. Since each peripheral tissue requires distinct methods to examine the biomarker and/or GALT effect, this highlights the necessity for alternative strategies to evaluate the overall impact of therapies.

CO scrubbing, zero gases, Keeling plots, and a mathematical approach to ameliorate the deleterious effects of ambient CO during C breath testing in humans and animals.

C breath testing is increasingly used in physiology and ecology research because of what it reveals about the different fuels that animals oxidize to meet their energetic demands. Here I review the practice of C breath testing in humans and other animals and describe the impact that contamination by ambient/background CO in the air can have on the accuracy of C breath measurements. I briefly discuss physical methods to avoid sample contamination as well as the Keeling plot approach that researchers have been using for the past two decades to estimate δ C from breath samples mixed with ambient CO .

Resting metabolic rates increase with elevation in a mountain-dwelling lizard.

Individuals that inhabit broad elevational ranges may experience unique environmental challenges. Because temperature decreases with increased elevation, the ectotherms living at high elevations have to manage limited activity time and high thermoregulatory effort. The resting metabolic rate (RMR) of a postabsorptive animal is related to its total energy requirements as well as many other fitness traits.

Environmental temperature alters the overall digestive energetics and differentially affects dietary protein and lipid use in a lizard.

Processing food (e.g. ingestion, digestion, assimilation) requires energy referred to as specific dynamic action (SDA) and is at least partially fuelled by oxidation of the nutrients (e.

Consequences of prey exoskeleton content for predator feeding and digestion: black widow predation on larval versus adult mealworm beetles.

Predators often feed on a wide range of prey that can vary in behavior, morphology, and physiology. The net benefits that predators gain from prey are likely related to both prey nutrient content and prey morphology or defenses. For invertebrates, the exoskeleton is a morphological trait that varies widely among species and during ontogeny and could affect nutrient extraction by predators.

Progressive behavioural, physiological and transcriptomic shifts over the course of prolonged starvation in ticks.

Ticks are obligatorily hematophagous but spend the majority of their lives off host in an unfed state where they must resist starvation between bouts of blood feeding. Survival during these extended off-host periods is critical to the success of these arthropods as vectors of disease; however, little is known about the underlying physiological and molecular mechanisms of starvation tolerance in ticks. We examined the bioenergetic, transcriptomic and behavioural changes of female American dog ticks, Dermacentor variabilis, throughout starvation (up to nine months post-bloodmeal).

Learning to starve: impacts of food limitation beyond the stress period.

Starvation is common among wild animal populations, and many individuals experience repeated bouts of starvation over the course of their lives. Although much information has been gained through laboratory studies of acute starvation, little is known about how starvation affects an animal once food is again available (i.e.

Maintenance of Distal Intestinal Structure in the Face of Prolonged Fasting: A Comparative Examination of Species From Five Vertebrate Classes.

It was recently shown that fasting alters the composition of microbial communities residing in the distal intestinal tract of animals representing five classes of vertebrates [i.e., fishes (tilapia), amphibians (toads), reptiles (leopard geckos), birds (quail), and mammals (mice)].

Exogenous stress hormones alter energetic and nutrient costs of development and metamorphosis.

Variation in environmental conditions during larval life stages can shape development during critical windows and have lasting effects on the adult organism. Changes in larval developmental rates in response to environmental conditions, for example, can trade off with growth to determine body size and condition at metamorphosis, which can affect adult survival and fecundity. However, it is unclear how use of energy and nutrients shape trade-offs across life-stage transitions because no studies have quantified these costs of larval development and metamorphosis.

Life-extending dietary restriction and ovariectomy each increase leucine oxidation and alter leucine allocation in grasshoppers.

Reduced reproduction and dietary restriction each extend lifespan in many animal models, but possible contributions of nutrient oxidation and allocation are largely unknown. Ovariectomy and eating 70% of ad libitum-feeding each extend lifespan in lubber grasshoppers. When feeding levels between the two groups are matched, ovariectomy increases fat and protein storage while dietary restriction reduces fat storage.

Sex differences in the utilization of essential and non-essential amino acids in Lepidoptera.

The different reproductive strategies of males and females underlie differences in behavior that may also lead to differences in nutrient use between the two sexes. We studied sex differences in the utilization of two essential amino acids (EAAs) and one non-essential amino acid (NEAA) by the Carolina sphinx moth (). On day one post-eclosion from the pupae, adult male moths oxidized greater amounts of larva-derived AAs than females, and more nectar-derived AAs after feeding.

Dehydration Causes Increased Reliance on Protein Oxidation in Mice: A Test of the Protein-for-Water Hypothesis in a Mammal.

During fasting, animals rely on a mixture of fats, carbohydrates, and proteins that are derived solely from endogenous sources. The relative contributions of these metabolic fuels chiefly depend on the duration of the fast, but other factors including previous diet, environmental temperature, and activity level can modulate the fuel mixture. It has long been held that endogenous proteins are spared from catabolism until the final stages of prolonged fasting and contribute a significant proportion of energy once the other metabolic fuels have been depleted.

More than just sugar: allocation of nectar amino acids and fatty acids in a Lepidopteran.

The ability to allocate resources, even when limited, is essential for survival and fitness. We examine how nutrients that occur in minute amounts are allocated among reproductive, somatic, and metabolic demands. In addition to sugar, flower nectars contain two macronutrients-amino acids and fatty acids.

Previous Repeated Exposure to Food Limitation Enables Rats to Spare Lipid Stores during Prolonged Starvation.

The risk of food limitation and, ultimately, starvation dates back to the dawn of heterotrophy in animals, yet starvation remains a major factor in the regulation of modern animal populations. Researchers studying starvation more than a century ago suggested that animals subjected to sublethal periods of food limitation are somehow more tolerant of subsequent starvation events. This possibility has received little attention over the past decades, yet it is highly relevant to modern science for two reasons.

Cold adaptation increases rates of nutrient flow and metabolic plasticity during cold exposure in Drosophila melanogaster.

Metabolic flexibility is an important component of adaptation to stressful environments, including thermal stress and latitudinal adaptation. A long history of population genetic studies suggest that selection on core metabolic enzymes may shape life histories by altering metabolic flux. However, the direct relationship between selection on thermal stress hardiness and metabolic flux has not previously been tested.

The postabsorptive and postprandial metabolic rates of praying mantises: Comparisons across species, body masses, and meal sizes.

The metabolic rate of an animal affects the amount of energy available for its growth, activity and reproduction and, ultimately, shapes how energy and nutrients flow through ecosystems. Standard metabolic rate (SMR; when animals are post-absorptive and at rest) and specific dynamic action (SDA; the cost of digesting and processing food) are two major components of animal metabolism. SMR has been studied in hundreds of species of insects, but very little is known about the SMR of praying mantises.

The speed and metabolic cost of digesting a blood meal depends on temperature in a major disease vector.

The energetics of processing a meal is crucial for understanding energy budgets of animals in the wild. Given that digestion and its associated costs may be dependent on environmental conditions, it is necessary to obtain a better understanding of these costs under diverse conditions and identify resulting behavioural or physiological trade-offs. This study examines the speed and metabolic costs - in cumulative, absolute and relative energetic terms - of processing a bloodmeal for a major zoonotic disease vector, the tsetse fly Glossina brevipalpis, across a range of ecologically relevant temperatures (25, 30 and 35°C).

(13)C-Breath testing in animals: theory, applications, and future directions.

The carbon isotope values in the exhaled breath of an animal mirror the carbon isotope values of the metabolic fuels being oxidized. The measurement of stable carbon isotopes in carbon dioxide is called (13)C-breath testing and offers a minimally invasive method to study substrate oxidation in vivo. (13)C-breath testing has been broadly used to study human exercise, nutrition, and pathologies since the 1970s.

How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint.

Digesting pythons quickly oxidize the proteins in their meals and save the lipids for later.

Pythons digesting rodent meals exhibit up to 10-fold increases in their resting metabolic rate (RMR); this increase in RMR is termed specific dynamic action (SDA). Studies have shown that SDA is partially fueled by oxidizing dietary nutrients, yet it remains unclear whether the proteins and the lipids in their meals contribute equally to this energy demand. We raised two populations of mice on diets labeled with either [(13)C]leucine or [(13)C]palmitic acid to intrinsically enrich the proteins and lipids in their bodies, respectively.

Carbon stable-isotope tracking in breath for comparative studies of fuel use.

Almost half a century ago, researchers demonstrated that the ratio of stable carbon isotopes in exhaled breath of rats and humans could reveal the oxidation of labeled substrates in vivo, opening a new chapter in the study of fuel use, the fate of ingested substrates, and aerobic metabolism. Until recently, the combined use of respirometry and stable-isotope tracer techniques had not been broadly employed to study fuel use in other animal groups. In this review, we summarize the history of this approach in human and animal research and define best practices that maximize its utility.

The magnitude of the naturally occurring isotopic enrichment of 13C in exhaled CO2 is directly proportional to exercise intensity in humans.

Due to various biochemical fractionation processes during lipid synthesis, the lipid molecules in the body contain substantially lower concentrations of 13C than the nonlipid molecules. Because of the isotopic differences between these two endogenous nutrient pools, any shift toward nonlipid fuel oxidation would be expected to increase in the δ13C of the exhaled breath. Interestingly, the possibility of whether or not an exercise-induced change actually occurs has been debated in literature for over two decades and researchers have still not reached a consensus.

Unique and shared responses of the gut microbiota to prolonged fasting: a comparative study across five classes of vertebrate hosts.

Many animals face unpredictable food sources and periods of prolonged fasting, which likely present significant challenges to gut microorganisms. While several studies have demonstrated that fasting impacts the gut microbiota, experiments have not been carried out in a comparative context. We used 16S rRNA gene sequencing to document changes in colonic and cecal microbiomes of animals representing five classes of vertebrates at four time points through prolonged fasting: tilapia, toads, geckos, quail, and mice.

Thermal acclimation and nutritional history affect the oxidation of different classes of exogenous nutrients in Siberian hamsters, Phodopus sungorus.

During acclimatization to winter, changes in morphology and physiology combined with changes in diet may affect how animals use the nutrients they ingest. To study (a) how thermal acclimation and (b) nutritional history affect the rates at which Siberian hamsters (Phodopus sungorus) oxidize different classes of dietary nutrients, we conducted two trials in which we fed hamsters one of three (13) C-labeled compounds, that is, glucose, leucine, or palmitic acid. We predicted that under acute cold stress (3 hr at 2°C) hamsters previously acclimated to cold temperatures (10°C) for 3 weeks would have higher resting metabolic rate (RMR) and would oxidize a greater proportion of dietary fatty acids than animals acclimated to 21°C.