Lipid Embolism in Obese Göttingen Minipigs

Viuff, Birgitte; Straarup, Ellen Marie; Nowak, Jette; Morgills, Line; Skydsgaard, Mikala; Sjögren, Ingrid; Wulff, Birgitte S.; Christoffersen, Berit Østergaard

doi:10.1177/0192623319880464

Cited by 4 publications

(4 citation statements)

References 36 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Bowman's space was often enlarged and in several of the animals this vacuolation could also be observed in a few and occasionally several tubuli. The changes were not further characterised but could represent lipid as previously described [36]. Moreover, mild, diffuse hypertrophy of adipocytes were recorded in all examined white adipose tissue (WAT) depots form the HFD fed animals (both males and females) (S4 Fig).…”

Section: Plos Onementioning

confidence: 72%

High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs

Lützhøft,

Bækgård,

Wimborne

et al. 2024

PLoS ONE

Self Cite

View full text Add to dashboard Cite

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistance. HFD-fed Göttingen Minipig therefore represents a relevant animal model for studying host-microbiota interactions. No significant differences between the castrated and ovariectomized minipigs were observed.

show abstract

Section: Plos Onementioning

confidence: 72%

High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs

Lützhøft,

Bækgård,

Wimborne

et al. 2024

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the kidney of same animal model, variable-sized vacuoles in glomeruli is observed and the glomerular capillaries are dilated due to lipid and sometimes erythrocytes are seen to be displaced in the capillaries. 40…”

Section: Embolus Blood Vessels (Figures 311-313)mentioning

confidence: 99%

“…Several types of emboli may be found in the porcine lung: lipid, 40 thromboembolus, or bacterial. These are described more fully in the Cardiovascular section.…”

Section: Commentmentioning

confidence: 99%

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Minipig

et al. 2021

Self Cite

View full text Add to dashboard Cite

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project ( www.toxpath.org/inhand.asp ) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in most tissues and organs from the minipig used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the internet ( http://www.goreni.org/ ). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

show abstract

“…As a novel porcine model of NASH, the side effects of dietary manipulation in pigs are less well known than in rodents, leaving the etiology and treatment approaches for these effects unstudied. Disease induction via diet manipulation has demonstrated side effects in other swine models of disease, but the currently available clinical data related to the impact of NASH diet in pigs appears to be incomplete and can lead to unreasonable speculations for studies involving pigs ( Schumacher-Petersen et al., 2019 ; Pedersen et al., 2020 ; Viuff et al., 2020 ). Understanding and handling of dietary-related side effects are vital for study staff when selecting animal models, veterinary staff when implementing monitoring plans, and animal research committees when evaluating proposed protocols.…”

Section: Introductionmentioning

confidence: 99%

Clinical characterization of a hypersensitivity mixed bacterial and fungal dermatitis in a translational model of porcine NASH

Felgendreff,

Lawrence,

Hosseiniasl

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

IntroductionThe development of animal models of chronic liver disease via diet modification is a promising avenue for translational research but can lead to unexpected side effects that impact model adoption. While these side effects are well characterized in rodent models of nonalcoholic steatohepatitis (NASH), limited knowledge of these effects exists for novel porcine models of NASH. To close this gap, the present study investigates the side effects of diet-based NASH induction in pigs, with a systematic analysis of the pathologic mechanisms underlying dermatitis development and evaluation of treatment approaches.MethodTwelve pigs (10 large domestic pigs, 2 Goettingen minipigs) were fed a methionine- and choline-deficient, high-fat diet for 8 weeks to induce NASH. A retrospective review of each animal’s clinical record was performed to identify the side effects of the diet. Following the identification of diet-associated dermatitis, severity was judged by using a novel gradation system that characterized the individual lesions and body regions resulting in a cumulative evaluation. In addition to this clinical assessment, the etiology of the dermatitis was investigated via histopathologic and microbiologic testing. Furthermore, the success of prophylactic and therapeutic treatment approaches was evaluated by considering dermatitis development and clinical course.ResultsAll study animals demonstrated unexpected side effects of the methionine- and choline-deficient, high fat diet. In addition to marked dermatitis, study pigs showed impaired weight gain and developed steatorrhea and anemia. Based on the skin gradation system, five animals developed severe dermatitis, four animals moderate dermatitis, and three animals mild diet-associated dermatitis. Histological and microbiological evaluation of the affected skin showed signs of a hypersensitivity reaction with secondary infection by bacteria and fungi. The analysis showed that preemptive bathing extended the lesion-free duration by nearly 20 days. Furthermore, bathing in combination with a targeted antibiotic treatment represented a helpful treatment approach for diet-associated dermatitis.ConclusionThe provision of a methionine- and choline-deficient, high fat diet represents an effective approach for inducing NASH liver disease in pigs but predisposes study animals to multiple side effects. These side effects are universal to animals on study but can be adequately managed and do not represent a significant limitation of this model.

show abstract

Lipid Embolism in Obese Göttingen Minipigs

Cited by 4 publications

References 36 publications

High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs

High fat diet is associated with gut microbiota dysbiosis and decreased gut microbial derived metabolites related to metabolic health in young Göttingen Minipigs

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Minipig

Clinical characterization of a hypersensitivity mixed bacterial and fungal dermatitis in a translational model of porcine NASH

Contact Info

Product

Resources

About