Characterization of Obese Phenotypes in a Small Nonhuman Primate, the Common Marmoset (<i>Callithrix jacchus</i>)

Tardif, Suzette D.; Power, Michael L.; Ross, Corinna N.; Rutherford, Julienne N.; Layne-Colon, Donna; Paulik, Mark

doi:10.1038/oby.2009.77

Cited by 75 publications

(105 citation statements)

References 44 publications

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“…Although highly variable due to dietary status and often associated with other complications such as type 2 diabetes and metabolic syndrome, elevated TG has been considered another independent risk factor for CHD by a number of studies ( 34 ). Among the animal models in our study that had similar omega-6 pathway-enriched FA compositions as humans in plasma CE, many showed elevated VLDL-c and/or TG levels, including several NHP models (dyslipidemic AGM, rhesus with metabolic syndrome, diabetic rhesus, and DIO rhesus), dog, hamster on HFD, and db/db mouse ( Table 1 ) ( 51,52 ). Statin treatment lowered VLDL-c and/or TG levels in all these models ( Table 2 ), suggesting that they are also useful as models for studying plasma remnant lipoprotein and TG metabolism and secondary risk prevention for dyslipidemic humans.…”

Section: Representative Preclinical Models For Dyslipidemic Populatiomentioning

confidence: 99%

Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia

Carballo-Jane

McLaren

et al. 2012

Journal of Lipid Research

189

168

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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide ( 1 ). Dyslipidemia has been shown to be one of the most potent risk factors for coronary heart disease (CHD) ( 2, 3 ). Dyslipidemia is characterized by elevated plasma cholesterol, especially low density lipoprotein cholesterol (LDL-c) levels. Management of dyslipidemia is considered throughout the primary and secondary prevention of CHD ( 4 ). For the past 20 years, the statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) class of cholesterol-lowering drugs has been used for the treatment of hypercholesterolemia, either alone or in combination with other classes of lipid-lowering drugs Abstract In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profi les in 24 models. These included fi ve mouse strains, six other nonprimate species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profi les, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study . -

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Section: Representative Preclinical Models For Dyslipidemic Populatiomentioning

confidence: 99%

Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia

Carballo-Jane

McLaren

et al. 2012

Journal of Lipid Research

189

168

View full text Add to dashboard Cite

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“…For comparative purposes, obesity in nonhuman primates should be defined relative to metabolic dysregulation similar to obesity-related disease in humans. For example, adult marmosets with body fat above 14% have higher fasting glucose, higher glycosylated hemoglobin, and higher fasting triglycerides, similar to metabolic syndrome in obese humans (Tardif et al, 2009). Therefore, we can label such marmosets obese.…”

Section: The Mismatch Paradigm and Our ''Captive'' Environmentmentioning

confidence: 99%

The human obesity epidemic, the mismatch paradigm, and our modern “captive” environment

Power

2012

American J Hum Biol

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In the distant past obesity in humans was rare and likely caused by metabolic dysregulation due to genetic or disease-related pathology. External factors precluded the ability of most people to overeat or under exert. Socio-cultural obesity came about due to the rareness of obesity and its difficulty to achieve. What is rare becomes valuable and what is difficult to achieve becomes a badge of prestige. The modern human obesity epidemic would appear to represent a third class of obesity: environmental obesity. Much like the captive environments which humans construct for the captive/companion animals in our care, the modern human environment has greatly decreased the challenges of life that would restrict food intake and enforce exertion. And like us, our captive/companion animal populations are also experiencing obesity epidemics. A further concern is that maternal obesity alters maternal signaling to offspring, in utero through the placenta and after birth through breast milk, in ways that perpetuate an enhanced vulnerability to obesity. Molecules such as leptin, produced by adipose tissue and placenta, have significant developmental effects on brain areas associated with feeding behavior. Leptin and other cytokines and growth factors are found in breast milk. These molecules have positive effects on gut maturation; their effects on metabolism and brain development are unclear. Placenta and brain also are hotspots for epigenetic regulation, and epigenetic changes may play significant roles in the later vulnerability to obesity and to the development of a diverse array of diseases, including heart disease, hypertension, and noninsulin-dependent diabetes. Am. J. Hum. Biol. 00:000-000, 2012.

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“…A small common marmoset colony was established at GlaxoSmithKline to serve as a preclinical model for drug discovery and development. Common marmosets develop diet-induced obesity phenotypes when placed on high fat diets and were employed in studies to help develop anti-obesity compounds (Tardif et al, 2009). Over the course of several years, complete necropsies were performed on 46 marmosets originating from this colony.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus)

Shen

Feng

Sheh

et al. 2015

Journal of Medical Microbiology

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Isolation and characterization of a novelHelicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus) Purpose-bred common marmosets from domestic sources housed in a US research facility, and used in multiple drug discovery programmes, were noted to have a high incidence of spontaneous inflammatory bowel disease and sporadic cholecystitis and cholangiohepatitis. Inflammatory infiltrates increased in incidence and severity with age. Because Helicobacter spp. have been linked to gastrointestinal diseases, samples from the gastrointestinal tracts of 39 marmosets were screened for Helicobacter spp. by culture and PCR. Helicobacter spp. were frequently detected in marmosets; 28.2 % of the marmosets were positive for a proposed novel species, Helicobacter jaachi sp. nov., by culture, and 48.7 % were positive by Helicobacter genus-specific PCR. Seventeen strains of Helicobacter sp. from 11 marmosets were cultured from various gastrointestinal sites. Older animals (age 6-11 years) had a higher helicobacter prevalence rate (57.1 %) compared with younger animals (age 3-5 years), which had a 27.2 % prevalence rate. Cells of H. jaachi sp. nov. were catalase, urease and oxidase positive and had fusiform morphology, with periplasmic fibres and multiple bipolar, sheathed flagella. All isolates had similar 16S and 23S rRNA sequences, which clustered as representatives of a novel Helicobacter species closely related to 'Helicobacter sanguini' (97 %), a species isolated from cotton-top tamarins and 'Helicobacter callitrichis' (96 %) isolated previously from the faeces of common marmosets. The whole genome sequence of one of the liver isolates, H. jaachi sp. nov. MIT 09-6949 T , had a 1.9 Mb genome length with a 41 mol% DNA G+C content. The type strain of Helicobacter jaachi sp. nov., MIT 09-6949 T , has been deposited in the BCCM/LMG Bacteria Collection as LMG 28613 T . These findings add to the increasing number of animal species with gastrointestinal disease in which novel enterohepatic Helicobacter spp. have been isolated. INTRODUCTIONThe common marmoset (Callithrix jacchus) has been utilized as a non-human primate model for nonclinical pharmaceutical development (Orsi et al., 2011). The common marmoset's importance as a model in biomedical research will be enhanced with the recent publication of its genome (Worley et al., 2014). An illustration of the marmoset's usefulness is its use in neuroscience research and genome editing technology (Kishi et al., 2014). A small common marmoset colony was established at GlaxoSmithKline to serve as a preclinical model for drug discovery and development. Common marmosets develop diet-induced obesity phenotypes when placed on high fat diets and were employed in studies to help develop anti-obesity compounds (Tardif et al., 2009). Over the course of several years, complete necropsies were performed on 46 marmosets originating from this colony. The spectrum of spontaneous pathology documented was similar to that reported in the literature for common marmoset...

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Characterization of Obese Phenotypes in a Small Nonhuman Primate, the Common Marmoset (Callithrix jacchus)

Cited by 75 publications

References 44 publications

Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia

Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia

The human obesity epidemic, the mismatch paradigm, and our modern “captive” environment

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus)

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