Plasma Proteome Profiles Associated with Diet-Induced Metabolic Syndrome and the Early Onset of Metabolic Syndrome in a Pig Model

Abstract

Obesity and related diabetes are important health threatening multifactorial metabolic diseases and it has been suggested that 25% of all diabetic patients are unaware of their patho-physiological condition. Biomarkers for monitoring and control are available, but early stage predictive biomarkers enabling prevention of these diseases are still lacking. We used the pig as a model to study metabolic disease because humans and pigs share a multitude of metabolic similarities. Diabetes was chemically induced and control and diabetic pigs were either fed a high unsaturated fat (Mediterranean) diet or a high saturated fat/cholesterol/sugar (cafeteria) diet. Physiological parameters related to fat metabolism and diabetes were measured. Diabetic pigs' plasma proteome profiles differed more between the two diets than control pigs plasma proteome profiles. The expression levels of several proteins correlated well with (patho)physiological parameters related to the fat metabolism (cholesterol, VLDL, LDL, NEFA) and diabetes (Glucose) and to the diet fed to the animals. Studying only the control pigs as a model for metabolic syndrome when fed the two diets showed correlations to the same parameters but now more focused on insulin, glucose and abdominal fat depot parameters. We conclude that proteomic profiles can be used as a biomarker to identify pigs with developing metabolic syndrome (prediabetes) and diabetes when fed a cafeteria diet. It could be developed into a potential biomarkers for the early recognition of metabolic diseases.

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].…”

Investigating the Metabolic Syndrome

“…Recently, MetS was successfully induced in large domestic pigs such as American Yorkshire (Sus scrofa domesticus) using high saturated-fat/cholesterol/sugar (te Pas et al , 2013) or high-fat/high-fructose diet. (Pawar et al , 2015, Ma et al , 2015) In domestic pigs, a 2% high-cholesterol diet causes only endothelial dysfunction and early changes of atherosclerosis, but not obesity, IR, or hypertension (Eirin et al , 2014, Urbieta-Caceres et al , 2010).…”

NMR-based metabolomics highlights differences in plasma metabolites in pigs exhibiting diet-induced differences in adiposity

“…Plasma concentrations of triglycerides were higher (P < 0.001), while plasma concentrations of β-hydroxybutyrate, leptin, glucose, insulin and urea were lower (P ≤ 0.05) in HF pigs than in LF pigs. Plasma been also related to early signs of diabetes in pigs used as a biomedical model and fed diets with different fatty acid contents [5]. NMR-based metabolomics is another emergent wide tool [6] including in pigs [7], which is fast and reliable to evaluate multiparametric metabolic responses.…”