Animal Models of Exercise and Obesity

2013 ◽  
Vol 31 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Christine E. Kasper

Animal models have been invaluable in the conduct of nursing research for the past 40 years. This review will focus on specific animal models that can be used in nursing research to study the physiologic phenomena of exercise and obesity when the use of human subjects is either scientifically premature or inappropriate because of the need for sampling tissue or the conduct of longitudinal studies of aging. There exists an extensive body of literature reporting the experimental use of various animal models, in both exercise science and the study of the mechanisms of obesity. Many of these studies are focused on the molecular and genetic mechanisms of organ system adaptation and plasticity in response to exercise, obesity, or both. However, this review will narrowly focus on the models useful to nursing research in the study of exercise in the clinical context of increasing performance and mobility, atrophy and bedrest, fatigue, and aging. Animal models of obesity focus on those that best approximate clinical pathology.

2010 ◽  
Vol 23 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Paul Guilloteau ◽  
Romuald Zabielski ◽  
Harald M. Hammon ◽  
Cornelia C. Metges

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.


2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.


1962 ◽  
Vol 17 (2) ◽  
pp. 239-242 ◽  
Author(s):  
Thomas F. Hornbein ◽  
Albert Roos

Hypoxia of mild degree (PaOO2 above 60 mm Hg) produces little or no ventilatory response in resting man during the steady state. To evaluate the possibility that the effectiveness of a hypoxic chemoreceptor drive might be enhanced by exercise, the ventilatory response to mild hypoxia was measured in two human subjects during rest and exercise. Though no significant increase in ventilation occurred at rest above a PaOO2 of 60 mm Hg, a decrease in PaOO2from 100 to 94 mm Hg produced a statistically significant increase in steady state ventilation during moderate exercise. In addition, temporary block of the sympathetic innervation to the carotid and aortic bodies in one subject resulted in a diminution of work hyperpnea. This suggests that increased sympathetic tone during exercise, by reducing blood flow through the chemoreceptors, might result in increased neural discharge and hence increased ventilation even though arterial POO2 is the same as at rest. Thus, activity of the chemoreceptors as modified by sympathetic control of their blood supply may be an important determinant of the ventilatory response to exercise. Since work hyperpnea is enhanced by even mild hypoxia, this ventilatory response may be sufficient to initiate respiratory acclimatization to altitudes so low that resting ventilation on acute exposure is unaffected. Submitted on July 31, 1961


2020 ◽  
Vol 23 (8) ◽  
pp. 524-532
Author(s):  
Thomas A Macek ◽  
Kazunori Suzuki ◽  
Karen Asin ◽  
Haruhide Kimura

Abstract Background TAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of the striatum. PDE10A hydrolyzes both cyclic adenosine monophosphate and cyclic guanosine monophosphate and modulates dopamine signaling downstream of receptor activation in both direct and indirect pathways of the striatum. TAK-063 exhibited antipsychotic-like effects in animal models; however, the translatability of these models to the clinical manifestations of schizophrenia and the meaningfulness for new targets such as PDE10A has not been established. Methods The TAK-063 phase 1 program included a comprehensive translational development strategy with the main objective of determining whether the antipsychotic-like pharmacodynamic effects seen in nonclinical models would translate to human subjects. To evaluate this objective, we conducted a single-rising dose study (84 healthy subjects), a positron emission tomography (PET) study (12 healthy subjects), a functional magnetic resonance imaging blood oxygen level-dependent (BOLD) study (27 healthy subjects), and a multiple-rising dose study that included people with schizophrenia (30 healthy Japanese subjects and 47 subjects with stable schizophrenia). In addition, assessments of cognition and electroencephalography (27 healthy subjects and 47 subjects with stable schizophrenia) were included. Results PDE10A engagement by TAK-063 was verified with a novel PET radiotracer for use in primates and humans. TAK-063 showed favorable pharmacokinetic and safety profiles in humans, and TAK-063 reduced ketamine-induced changes in electroencephalography and BOLD signaling in animal models and healthy human subjects. In addition, analogous effects on cognition were observed in animal models and human subjects. Conclusions Overall, the phase 1 results showed some consistent evidence of antipsychotic activity. This translational strategy may be valuable for the future development of novel therapeutic approaches, even when relevant nonclinical models are not available.


1999 ◽  
Vol 69 (2) ◽  
pp. 92-95 ◽  
Author(s):  
Chopra ◽  
Bhagavan

There are several reports in the literature on the relative bioavailabilities of RRR (natural) vs. all-rac (synthetic) forms of vitamin E in humans and animal models but none on the bioavailability of alpha-tocopherol in mixed vitamin E formulations. In the present study we examined the bioavailability of alpha-tocopherol in a typical commercially available product containing mixed tocopherols. We also tested a formulation containing all-rac-alpha-tocopherol with mixed tocopherols for purposes of comparison along with straight RRR-and all-rac-alpha-tocopheryl acetate as reference products. Normal male subjects were given one of the four formulations of vitamin E (800 IU per day in softgel capsule form for 10 days): 1. All-rac-alpha-tocopheryl acetate, 2. RRR-alpha-tocopheryl acetate, 3. RRR-alpha-tocopherol with mixed tocopherols, and 4. all-rac-alpha-tocopherol with mixed tocopherols. Both serum alpha- and gamma-tocopherols were determined by HPLC at baseline, and at days 2, 4, 7 and 10. The values for alpha- at baseline and 10 days were 0.80, 0.80, 0.80 & 0.79 mg/dl and 1.67, 1.72, 1.76 & 1.62 mg/dl. The values for gamma- were 0.28, 0.29, 0.30 & 0.29 mg/dl and 0.11, 0.08, 0.10 & 0.10 mg/dl. Thus the data show that a) the bioavailability of RRR-and all-rac-alpha-tocopherols is not affected by other tocopherols, and b) both RRR-and all-rac-alpha-tocopherol (free or esterified) significantly suppress the serum gamma tocopherol to the same extent. Furthermore, since there was no difference in the serum values of alpha-tocopherol between RRR-and all-rac-vitamin E given the same dose as IUs, the data also support the currently accepted ratio of 1.36 for the biopotency of RRR- vs. all-rac-alpha-tocopheryl acetate.


2011 ◽  
Vol 35 (3) ◽  
pp. 264-269 ◽  
Author(s):  
David S. Senchina

Student researchers in physiology courses often interact with human subjects in classroom research but may be unfamiliar with the professional ethics of experimenter-subject interactions. This communication describes experiences related to an interactive video used in exercise science and general biology courses to help students become aware of, sensitive to, and comfortable with implementing professional ethics into their own thinking and behavior as researchers before entering the laboratory. The activity consisted of a filmed exercise physiology experiment complemented with interactive question sheets followed by small- and large-group discussion and culminating with individual student reflections. Student written responses from multiple courses indicated that students were able to 1) identify and consider the ethics of experimenter-subject interactions from the movie, 2) generalize broader ideas of professional ethics from those observations, and 3) consider their observations in terms of future experiments they would be conducting personally and how they should interact with human subjects. A majority of students indicated a positive reaction to the video and identified specific aspects they appreciated. It is hoped that this report will encourage other instructors to consider the use of interactive videos in the teaching and learning of professional ethics related to their courses.


2018 ◽  
Author(s):  
Harrison McAdams ◽  
Aleksandra Sasha Igdalova ◽  
Manuel Spitschan ◽  
David H. Brainard ◽  
Geoffrey K. Aguirre

AbstractPurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally-narrowband stimuli.Methods3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were “silent substitution” cone‐ and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape.ResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone‐ and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light.ConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.


2021 ◽  
Vol 11 ◽  
Author(s):  
Joshua P. Nederveen ◽  
Geoffrey Warnier ◽  
Alessia Di Carlo ◽  
Mats I. Nilsson ◽  
Mark A. Tarnopolsky

The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or ‘exerkines’). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers or ‘mediators’ of intercellular communication. Given these findings, there has been a rapidly growing interest in the role of EVs in the multi-systemic, adaptive response to exercise. This review aims to summarize our current understanding of the effects of exercise on MVs and ELVs, examine their role in the exercise response and long-term adaptations, and highlight the main methodological hurdles related to blood collection, purification, and characterization of ELVs.


Author(s):  
Erich S. Franz ◽  
Sarah E. Chancellor ◽  
Lee E. Goldstein

Adult cognitive disorders exact a staggering burden on worldwide health care, with the need for efficacious and accessible treatments growing every day. The ability to probe questions relevant to normal or aberrant cognition in humans makes animal models indispensable tools in translational research. The use of animal models enables detailed investigation of complex interactions between genes, environment, and cognition that would be difficult or impossible in human subjects or populations. However, special consideration must be given to create specific, translatable models of human cognitive disorders. First, a model must prove statistically reliable, reproducible, and valid. Successful translational research requires thoughtful consideration and careful deployment of reliable, well-chosen animal models that are appropriately matched to their experimental purpose. In addition, to ensure specificity of a model to one disorder, it is prudent to focus on clusters of clinical features and disease-specific phenotypes in addition to environmental and genetic risk factors. Many neurological disorders share symptomatic elements in common, which drives the necessity for relevant cognitive domains to the disease in question to be carefully considered and replicated. Thoughtfully created animal models facilitate translational research aimed at understanding disease mechanisms and developing effective diagnostics, therapeutics, and preventive strategies to achieve better health care outcomes for people affected by cognitive disorders.


2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Megan E. Spurgeon ◽  
Paul F. Lambert

ABSTRACT Animal models of viral pathogenesis are essential tools in human disease research. Human papillomaviruses (HPVs) are a significant public health issue due to their widespread sexual transmission and oncogenic potential. Infection-based models of papillomavirus pathogenesis have been complicated by their strict species and tissue specificity. In this Gem, we discuss the discovery of a murine papillomavirus, Mus musculus papillomavirus 1 (MmuPV1), and how its experimental use represents a major advancement in models of papillomavirus-induced pathogenesis/carcinogenesis, and their transmission.


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