Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

Abstract

The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2-to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…With advances in the breeding of minipigs and micropigs, the use of pigs in biomedical and orthopaedic research has increased [152]. Regarding bone anatomy, microstructure, remodelling and healing, porcine bone closely resembles human bone [153,154].…”

“…Regarding bone anatomy, microstructure, remodelling and healing, porcine bone closely resembles human bone [153,154]. Pigs were found to exhibit spontaneous vertebral fracture and their rates of bone removal and deposition (trabecular and cortical bones) are similar to humans although porcine bone remodels slightly faster than human bone [152,155,156]. Limitations for the use of NHP in regulatory toxicology studies have opened discussions on the suitability of using minipigs in drug development studies [157].…”

The effect of high-fat diet on the composition of the gut microbiota in cloned and non-cloned pigs of lean and obese phenotype

“…Pigs are generally considered to be good animal models for studying human diseases, mainly due to their similar physiology. 1 However, one factor in such experimental studies is the inter-individual variations between animals. Cloning of animals such as pigs may provide an animal model with smaller inter-individual variation than normally bred siblings, thereby enhancing experimental control and standardization…”

Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

“…In general, pigs have a huge potential as biomedical models because of their human-like physiology and metabolic features. Specifically they should be uniquely useful as models for the obesity-induced inflammation-related host reactions thought to underlie development of disease related to obesity (the metabolic syndrome) (Litten-Brown et al, 2010). Although it is normally assumed that the use of cloned animals will exhibit less interindividual phenotypic variation and allow for a reduction of the number of animals needed to obtain statistically sound data, this assumption has been found not always to be warranted.…”