TY - JOUR
T1 - Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: Form food intake to metabolic disease
AU - Koopmans, S.J.
AU - Schuurman, T.
PY - 2015
Y1 - 2015
N2 - (Mini)pigs have proven to be a valuable animal model in nutritional, metabolic and cardiovascular research and in some other biomedical research areas (toxicology, neurobiology). The large resemblance of (neuro)anatomy, the gastro-intestinal tract, body size, body composition, and the omnivorous food choice and appetite of the pig are additional reasons to select this large animal species for (preclinical) nutritional and pharmacological studies. Both humans and pigs are prone to the development of obesity and related cardiovascular diseases such as hypertension and atherosclerosis. Bad cholesterol (LDL) is high and good cholesterol (HDL) is low in pigs, like in humans. Disease-relevant pig models fill the gap between rodent models and primate species including humans. Diet-induced obese pigs show a phenotype related to the metabolic syndrome including high amounts of visceral fat, fatty organs, insulin resistance and high blood pressure. However, overt hyperglycaemia does not develop within 6 months after initiation of high sugar-fat feeding. Therefore, to accelerate the induction of obese type 2 diabetes, obese pigs can be titrated with streptozotocin, a chemical agent which selectively damages the insulin-producing pancreatic beta-cells. However, insulin is required to maintain obesity. With proper titration of streptozotocin, insulin secretion can be restrained at such a level that hyperglycaemia will be induced but lipolysis is still inhibited due to the fact that inhibition of lipolysis is more sensitive to insulin compared to stimulation of glucose uptake. This strategy may lead to a stable hyperglycaemic, non-ketotic obese pig model which remains anabolic with time without the necessity of exogenous insulin treatment.
AB - (Mini)pigs have proven to be a valuable animal model in nutritional, metabolic and cardiovascular research and in some other biomedical research areas (toxicology, neurobiology). The large resemblance of (neuro)anatomy, the gastro-intestinal tract, body size, body composition, and the omnivorous food choice and appetite of the pig are additional reasons to select this large animal species for (preclinical) nutritional and pharmacological studies. Both humans and pigs are prone to the development of obesity and related cardiovascular diseases such as hypertension and atherosclerosis. Bad cholesterol (LDL) is high and good cholesterol (HDL) is low in pigs, like in humans. Disease-relevant pig models fill the gap between rodent models and primate species including humans. Diet-induced obese pigs show a phenotype related to the metabolic syndrome including high amounts of visceral fat, fatty organs, insulin resistance and high blood pressure. However, overt hyperglycaemia does not develop within 6 months after initiation of high sugar-fat feeding. Therefore, to accelerate the induction of obese type 2 diabetes, obese pigs can be titrated with streptozotocin, a chemical agent which selectively damages the insulin-producing pancreatic beta-cells. However, insulin is required to maintain obesity. With proper titration of streptozotocin, insulin secretion can be restrained at such a level that hyperglycaemia will be induced but lipolysis is still inhibited due to the fact that inhibition of lipolysis is more sensitive to insulin compared to stimulation of glucose uptake. This strategy may lead to a stable hyperglycaemic, non-ketotic obese pig model which remains anabolic with time without the necessity of exogenous insulin treatment.
KW - Cardiovascular disease
KW - Ethics
KW - Food intake
KW - Gut-brain axis
KW - Metabolic syndrome
KW - Obesity
KW - Pig
KW - Swine
KW - Type 2 diabetes
U2 - 10.1016/j.ejphar.2015.03.044
DO - 10.1016/j.ejphar.2015.03.044
M3 - Article
SN - 0014-2999
VL - 759
SP - 231
EP - 239
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -