Adipose tissue remodeling in a novel domestic porcine model of diet-induced obesity

Abstract

Objective To establish and characterize a novel domestic porcine model of obesity. Design and Methods Fourteen domestic pigs were fed normal (lean, n=7) or high-fat/high-fructose diet (obese, n=7) for 16 weeks. Subcutaneous abdominal adipose tissue biopsies were obtained after 8, 12 and 16 weeks of diet, and pericardial adipose tissue after 16 weeks, for assessments of adipocyte size, fibrosis, and inflammation. Adipose tissue volume and cardiac function were studied with multi-detector computed-tomography, and oxygenation with magnetic resonance imaging. Plasma lipids profiles, insulin resistance, and markers of inflammation were evaluated. Results Compared with lean, obese pigs had elevated cholesterol and triglycerides levels, blood pressure, and insulin resistance. Both abdominal and pericardial fat volume increased after 16 weeks of obese. In abdominal subcutaneous adipose tissue, adipocyte size and both tumor necrosis factor (TNF)-α expression progressively increased. Macrophage infiltration showed in both abdominal and pericardial adipose tissues. Circulating TNF-α increased in obese only at 16 weeks. Compared with Lean, obese pigs had similar global cardiac function, but myocardial perfusion and oxygenation were significantly impaired. Conclusion A high-fat/high-fructose diet induces in domestic pigs many characteristics of metabolic syndrome, which is useful to investigate the effects of the obesity.

Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research

“…In addition, 1% to 2% purified cholesterol was added in most diet-induced obesity pig models. High-fat diet feeding with the addition of cholesterol led to dyslipidemia (elevated total cholesterol, low-density lipoprotein, and high-density lipoprotein) [42,163,168,[171][172][173] and to a lesser extent without the addition of cholesterol [167,170,174,175]. Dietary-induced hepatic steatosis was reported in minipig breeds [42,174] and domestic pigs [173].…”

“…However, studies vary in terms of numerous parameters, such as pig breed (domestic vs. minipig), age (adolescent vs. adult), gender, diet type (purified vs. grain-based or mix), diet composition (carbohydrate, fat, protein source, and content), energy content (metabolizable energy/kg food), feeding regimen (restricted vs. ad libitum), calorie supply per day, and feeding duration, making comparisons difficult [42,161,163,[167][168][169][170][171][172][173][174][175][176]. In addition, not all phenotypic characteristics relevant for metabolic syndrome are evaluated in each study.…”

“…Body weight was significantly increased compared to normal diet feeding, with its magnitude depending on the feeding duration, diet composition, and energy intake [42,163,167,[170][171][172][173][174][175]. In a few of the studies, body composition was determined, showing that the animals developed a significantly elevated fat mass as a consequence of high-energy intake [167,170,175].…”

“…Interestingly, high-fructose feeding was not accompanied by morphologic alterations in the liver [42,174] despite the fact that fructose might be linked to the development of nonalcoholic fatty liver disease in humans (reviewed in [178]). High-fat feeding reduced insulin sensitivity (insulin levels during intravenous glucose tolerance test [IVGTT], insulin tolerance test [ITT], or determination of the homeostatic model assessment index for insulin resistance [HOMA-IR]) [42,163,170,171,174] in minipig breeds and domestic pigs, whereas fasting insulin levels were only rarely affected [42]. Inconsistently, impaired glucose tolerance was observed [163,174,175].…”

Original Research: Orexins A and B stimulate proliferation and differentiation of porcine preadipocytes

“…The rationale behind using porcine animal and cellular models is reflected by striking similarities between humans and pigs, including both being omnivores, fat deposition, as well as similar adipocytes size. [17][18][19][20] Therefore, identification of novel factors able to influence preadipocytes proliferation and differentiation may significantly improve our understanding of porcine adipogenesis and understanding of obesity in general. Furthermore, characterization of novel targets with the capability to modulate fat tissue formation may contribute to the development of porcine breeding programs.…”