Disconnect between adipose tissue inflammation and cardiometabolic dysfunction in Ossabaw pigs

Abstract

ObjectiveThe Ossabaw pig is emerging as an attractive model of human cardiometabolic disease due to its size and susceptibility to atherosclerosis, among other characteristics. Here we investigated the relationship between adipose tissue inflammation and metabolic dysfunction in this model.MethodsYoung female Ossabaw pigs were fed a western-style high-fat diet (HFD) (n=4) or control low-fat diet (LFD) (n=4) for a period of 9 months and compared for cardiometabolic outcomes and adipose tissue inflammation.ResultsThe HFD-fed “OBESE” pigs were 2.5 times heavier (p<0.001) than LFD-fed “LEAN” pigs and developed severe obesity. HFD-feeding caused pronounced dyslipidemia, hypertension, insulin resistance (systemic and adipose) as well as induction of inflammatory genes, impairments in vasomotor reactivity to insulin and atherosclerosis in the coronary arteries. Remarkably, visceral, subcutaneous and perivascular adipose tissue inflammation (via FACS analysis and RT-PCR) was not increased in OBESE pigs, nor were circulating inflammatory cytokines.ConclusionsThese findings reveal a disconnect between adipose tissue inflammation and cardiometabolic dysfunction induced by western diet feeding in the Ossabaw pig model.

The Ossabaw Pig Is a Suitable Translational Model to Evaluate Dietary Patterns and Coronary Artery Disease Risk

“…At the end of our 6-mo feeding period mean body weights, lipid and lipoprotein profile, and glucose, insulin, inflammatory marker, and liver enzyme concentrations were very similar to those observed in pigs fed the atherogenic diet (20,21,38,45). Our histopathologic findings of early-stage atherosclerotic lesions in pigs fed the WD are consistent with the early neointimal hyperplasia and increased degree of atheroma (percentage) in the LAD and LCX observed in obese pigs fed the atherogenic diet, confirmed via histopathology or intravascular ultrasound (19,44,45). Thus, our data document the suitability of the Ossabaw pig as a model of early-stage atherosclerosis induced by feeding a diet that closely mimics a human WD pattern, thereby increasing the translational nature of this model.…”

“…syrup, and 43-45%E from fat sources including hydrogenated coconut oil, soybean oil, or lard, with supplementation of cholesterol at 2% wt:wt) in caloric excess relative to a low-fat "control" diet (18%E from protein, 71%E from carbohydrate, and 11%E from fat) results in obesity and the manifestation of several pathologic aspects of the metabolic syndrome, as well as insulin resistance and atherosclerosis (19)(20)(21)(22)(38)(39)(40)(41)(42)(43)(44). Compared with the atherogenic diet, the WD used in our study had a lower proportion of fat, carbohydrate, and cholesterol.…”

Response to "Perivascular adipose tissue and inflammation

“…Dr. Goodwill correctly summarized our main findings, which were that Ossabaw swine fed a Western diet develop many cardiometabolic impairments, including insulin resistance and atherosclerotic disease, yet are apparently protected from adipose tissue inflammation (1). In response to his first concern regarding the validity of our ex vivo adipose tissue-conditioned media experiments, we agree that there are limitations to this tissue culture approach, and on their own, the conditioned media experiments should not be used to assess the inflammatory state of the tissue.…”

Molecular cloning of SLC35D3 and analysis of its role during porcine intramuscular preadipocyte differentiation

“…Obesity is a complex disease, it is influenced by genetic, environmental, and phenotypic factors [10][11][12], but the underlying mechanisms are not well understood [13]. Obesity is mainly determined by genetic differences [14], thus identification of the genes involved in fat deposition is of great interest.…”