Obesity Development in a Miniature Yucatan Pig Model: A Multi-compartmental Metabolomics Study on Cloned and Normal Pigs Fed Restricted or Ad Libitum High-Energy Diets

Curtasu, Mihai Victor; Knudsen, Knud Erik Bach; Callesen, Henrik; Purup, Stig; Stagsted, Jan; Hedemann, Mette Skou

doi:10.1021/acs.jproteome.8b00264

Cited by 23 publications

(28 citation statements)

References 61 publications

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“…The heavy fat accumulation created a preclinical stage with increased fasting glucose, signs of insulin deregulation and mild signs of liver inflammation (online Supplementary Table ). Similar effects have been found in other studies with Göttingen minipigs (22,31,32) .…”

Section: Discussionsupporting

confidence: 91%

“…The current study intended to investigate the possible ameliorating effects of DF and protein on MetS biomarkers in an obese porcine model for childhood obesity (22) . The daily feed intake for 6–9-month-old female minipigs is restricted to 300–400 g in order to prevent obesity (30) .…”

Section: Discussionmentioning

confidence: 99%

“…Before (week 20 of ad libitum feeding with LOFLOP) and after the intervention (week 28), fasting blood and tissue samples were taken as described in detail by Curtasu (22) . Briefly, after an overnight fasting (feed removed at 15·00), the minipigs were anaesthetised with 0·1 ml/kg BW of Zolitil mixture containing 50 mg/ml tiletamine/zolazepam (Vibrac SA, Carros, France), 2·5 mg/ml butorphanol (Torbugesic® Vet, Scan Vet Animal Health A/S), 12·5 mg/ml ketamine (Ketaminol Vet, Intervet Denmark) and 12·5 mg/ml xylazine (Rompun, Bayer Health Care AG), and blood samples were collected from the jugular vein by veno-puncture.…”

Section: Methodsmentioning

confidence: 99%

“…Although DF and protein have been the subject of many investigations, the interactive effects of DF and protein are poorly understood. In the present study, we investigated the possible ameliorating effects on MetS biomarkers in an obese porcine model for childhood obesity (22) by the use of enzyme-treated wheat bran as DF supplement and hydrolysed whey protein as protein supplement alone or combined. Göttingen minipigs have a small body size and have previously been used for the development of MetS models because of the anatomical and physiological similarities with adolescent and adult humans (23,24) .…”

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confidence: 99%

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Dietary fibre and protein do not synergistically influence insulin, metabolic or inflammatory biomarkers in young obese Göttingen minipigs

Curtasu

Knudsen

et al. 2020

Br J Nutr

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The effects of dietary fibre (DF) and protein on insulin response, lipidemia and inflammatory biomarkers were studied in a model experiment with juvenile obese Göttingen Minipigs. After 20 weeks feeding on a high-fat fructose-rich low-DF diet, forty-three 30-week old minipigs (31.3 ± 4.0 kg body weight) were allocated to low or high DF and protein diets for 8 weeks in a 2 × 2 factorial design. High DF contents decreased (P = 0.006) while high protein increased (P < 0.001) the daily gain. High protein contents increased fasting plasma concentrations of glucose (P = 0.008), non-esterified fatty acid (P =0.015), ghrelin (P = 0.008) and non-fasting LDL:HDL ratios (P = 0.015). High DF increased ghrelin (P = 0.036) and C-peptide levels (P = 0.011) in the non-fasting state. High protein increased the gene expression of fructose-bisphosphatase 1 in liver tissue (P = 0.043), whereas DF decreased fatty acid synthase expression in adipose tissue (P = 0.035). Interactions between DF and protein level were observed in the expression of leptin receptor in adipose tissue (P = 0.031) and of peroxisome-proliferator activated receptors-γ in muscle (P = 0.018) and adipose tissue (P = 0.004). In conclusion, high DF intake reduced weight gain and had potential benefit on beta-cell secretory function, but without effect on the lipid profile in this young obese model. High dietary protein by supplementing with whey protein did not improve insulin sensitivity or lipidemia, and combining high DF with high protein did not alleviate the risk of metabolic abnormalities.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Dietary fibre and protein do not synergistically influence insulin, metabolic or inflammatory biomarkers in young obese Göttingen minipigs

Curtasu

Knudsen

et al. 2020

Br J Nutr

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“…The limited number of pig templates that do exist include the domestic pig (Saikali et al, 2010), the neonatal piglet (Conrad et al, 2014), and the Göttingen minipig (Watanabe et al, 2001). The Yucatan is known to be gentle, has an adult weight ranging from approximately 70 to 90 kg (150 to 200 lbs), and has been used extensively for developing surgical and experimental techniques as well as models for metabolic syndrome, biocompatability, skin lesions, pharmacology, toxicology, and cardiovascular disease (Estrada et al, 2008;Eubanks et al, 2006;Curtasu et al, 2019;Mattern et al, 2007;Quesson et al, 2011;Montezuma et al, 2006;Pak et al, 2006;Lin et al, 1998;Hurtig et al, 2019;Swindle et al, 1990Swindle et al, , 2011Witczak et al, 2006;Lopez et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

MRI Brain Templates of the Male Yucatan Minipig

Norris¹,

Lisinski

Fievisohn³

et al. 2020

Preprint

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The pig is growing in popularity as an experimental animal because its gyrencephalic brain is similar to humans. Currently however, there is a lac of appropriate brain templates to support functional and structural neuroimaging pipelines. The primary contribution of this work is an averag volume from an iterative, non-linear registration of 70 male Yucatan minipig subjects whose ages ranged from five to seven months. In addition, several aspects of this study are unique, including the comparison of linear and non-linear template generation, the characterization of a large and homogeneous cohort, an analysis of effective resolution after averaging, and the evaluation of potential within template bias as well as a comparison with a template from another minipig species using a "left-out" validation set. We found that within our highly homogeneous cohort, non-linear registration produced better templates, but only marginally so. Although our T1-weighted data were resolution limited, we preserved effective resolution across the multi-subject average, produced templates that have high gray-white matter contrast, and demonstrated superior registration accuracy compared to the only known alternative minipig template.

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In vivo electrochemical lipolysis of fat in a Yucatan pig model: A proof of concept study

et al. 2022

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Objectives Traditional fat contouring is now regularly performed using numerous office‐based less invasive techniques. However, some limitations of these minimally invasive techniques include high cost or limited selectivity with performing localized contouring and reduction of fat. These shortcomings may potentially be addressed by electrochemical lipolysis (ECLL), a novel approach that involves the insertion of electrodes into tissue followed by application of a direct current (DC) electrical potential. This results in the hydrolysis of tissue water creating active species that lead to fat necrosis and apoptosis. ECLL can be accomplished using a simple voltage‐driven system (V‐ECLL) or a potential‐driven feedback cell (P‐ECLL) both leading to water electrolysis and the creation of acid and base in situ. The aim of this study is to determine the long‐lasting effects of targeted ECLL in a Yucatan pig model. Methods A 5‐year‐old Yucatan pig was treated with both V‐ECLL and P‐ECLL in the subcutaneous fat layer using 80:20 platinum:iridium needle electrodes along an 8 cm length. Dosimetry parameters included 5 V V‐ECLL for 5, 10, and 20 minutes, and −1.5 V P‐ECLL, −2.5 V P‐ECLL, −3.5 V P‐ECLL for 5 minutes. The pig was assessed for changes in fat reduction over 3 months with digital photography and ultrasound. After euthanasia, tissue sections were harvested and gross pathology and histology were examined. Results V‐ECLL and P‐ECLL treatments led to visible fat reduction (12.1%–27.7% and 9.4%–40.8%, respectively) and contour changes across several parameters. An increased reduction of the superficial fat layer occurred with increased dosimetry parameters with an average charge transfer of 12.5, 24.3, and 47.5 C transferred for 5 V V‐ECLL for 5, 10, and 20 minutes, respectively, and 2.0, 11.5, and 24.0 C for −1.5 V P‐ECLL, −2.5 V P‐ECLL, −3.5 V P‐ECLL for 5 minutes, respectively. These dose‐dependent changes were also evidenced by digital photography, gross pathology, ultrasound imaging, and histology. Conclusions ECLL results in selective damage and long‐lasting changes to the adipose layer in vivo. These changes are dose‐dependent, thus allowing for more precise contouring of target areas. P‐ECLL has greater efficiency and control of total charge transfer compared to V‐ECLL, suggesting that a low‐voltage potentiostat treatment can result in fat apoptosis equivalent to a high‐voltage DC system.

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Obesity Development in a Miniature Yucatan Pig Model: A Multi-compartmental Metabolomics Study on Cloned and Normal Pigs Fed Restricted or Ad Libitum High-Energy Diets

Abstract: This is the accepted manuscript (post-print version) of the article.Contentwise, the accepted manuscript version is identical to the final published version, but there may be differences in typography and layout.

Cited by 23 publications

References 61 publications

Dietary fibre and protein do not synergistically influence insulin, metabolic or inflammatory biomarkers in young obese Göttingen minipigs

Dietary fibre and protein do not synergistically influence insulin, metabolic or inflammatory biomarkers in young obese Göttingen minipigs

MRI Brain Templates of the Male Yucatan Minipig

In vivo electrochemical lipolysis of fat in a Yucatan pig model: A proof of concept study

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