Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

Abstract

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days-old) Duroc breed females (n=20) either with a standard growth diet (3800 KCal/day) or one with a high-calorie content (5200 KCal/day) during 70 days. Computerized tomography, massspectrometry based metabolomics, and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia, in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride, and sterol classes) were also linked with obesity-traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.

Hippocampal neurogenesis and Arc expression are enhanced in high-fat fed prepubertal female pigs by a diet including omega-3 fatty acids and Bifidobacterium breve CECT8242

“…Nevertheless, the HF diet used in this study did not lead to quantitative changes in both the analyzed neural plasticity markers in the DG of female piglets. Our results lend support to the assertion that there is an absence of an established metabolic syndrome in these animals at 19 weeks of age, as reported in recently published reports of Jove et al [ 32 ], Ballester et al [ 31 ] and Valent et al [ 33 ]. Their findings integrate with the present results into a multidisciplinary study analyzing the effect of the four dietary treatments and show that the administration of this HF diet caused some anomalies that could trigger the emergence of the metabolic syndrome.…”

“…Same sex littermates, from same father and mother, were randomly distributed into 4 experimental groups, using a matched pairs experimental design. After weaning, piglets were transferred to the IRTA pig experimental station, and subjected to the same management procedures as described in Ballester et al [ 31 ] and Jove et al [ 32 ]. Briefly, at 9 weeks of age, animals were located in environmentally monitored facilities, randomly distributed into 4 pens (10–11 animals per pen from different litters) and fed ad libitum for 10 weeks with 4 different dietary treatments giving rise to four different experimental groups: (T1) a conventional (and balanced) growth diet according to Nutrition Resource Centre (NRC) recommendations used as a control diet; (T2) a western-type diet formulated with a high fat and high saccharose content and protein of animal origin (caseinate); (T3) a western-type diet in which 50% of the protein was substituted for protein of vegetal origin (rice hydrolysate) and including 5 × 1010 cfu/day B. breve probiotic CECT8242; and T4) a diet similar to T3, supplemented with omega-3 fatty acid (1 g stearidonic acid and 2 g docosahexaenoic acid per 100 g fat) (Fig.…”

Decreased Hyocholic Acid and Lysophosphatidylcholine Induce Elevated Blood Glucose in a Transgenic Porcine Model of Metabolic Disease

“…Grace et al [35] also found that postprandial plasma PS (38:4) was significantly increased in patients with T2DM after physical activity. Recent research on Duroc pigs fed a high-calorie diet [36] found that PS (O-38:1), PS (P-39:0), PS (P-40:1), PS (O-40:5), PS (43:0), and PS (43:1) were significantly increased in pigs with prepubertal obesity, among which PS (21:0/22:0) was positively correlated with pig visceral fat content and human BMI. In this study, seven PSs were significantly changed between groups.…”

High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage

“…Same-sex littermates, from the same father and mother, were randomly distributed into 4 experimental groups using a matched-pairs experimental design. After weaning, piglets were transferred to the IRTA pig experimental station and subjected to the same management procedures as described [23,26]. Briefly, at 9 weeks of age, animals were located in environmentally monitored facilities, randomly distributed into 4 pens (10-11 animals per pen from different litters), and fed ad libitum for 10 weeks with 4 different dietary treatments, giving rise to four different experimental groups (see below).…”