Abstract
Forty percent of American women are obese and at risk for type II diabetes, impaired immune function, and altered microbiome diversity, thus impacting overall health. We investigated whether obesity induced by an excess calorie, high fat diet containing hydrogenated fats, fructose, and coconut oil (HFD) altered glucose homeostasis, peripheral immunity, and urogenital microbial dynamics. We hypothesized that HFD would cause hyperglycemia, increase peripheral inflammation, and alter urogenital microbiota to favor bacterial taxonomy associated with inflammation. We utilized female Ossabaw mini-pigs to model a ‘thrifty’ metabolic phenotype associated with increased white adipose tissue mass. Pigs were fed HFD (~4570 kcal/pig/day) or lean (~2000 kcal/pig/day) diet for a total of 9 estrous cycles (~6 months). To determine the effect of cycle stage on cytokines and the microbiome, animals had samples collected during cycles 7 and 9 on certain days of the cycle: D1, 4, 8, 12, 16, 18. Vaginal swabs or cervical flushes assessed urogenital microbiota. Systemic fatty acids, insulin, glucose, and cytokines were analyzed. Pig weights and morphometric measurements were taken weekly. Obese pigs had increased body weight, length, heart and belly girth but similar glucose concentrations. Obese pigs had decreased cytokine levels (IL-1β, TNF-α, IL-4, IL-10), arachidonic acid and plasma insulin, but increased levels of vaccenic acid. Obese pigs had greater urogenital bacterial diversity, including several taxa known for anti-inflammatory properties. Overall, induction of obesity did not induce inflammation but shifted the microbial communities within the urogenital tract to an anti-inflammatory phenotype. We postulate that the coconut oil in the HFD oil may have supported normal glucose homeostasis and modulated the immune response, possibly through regulation of microbial community dynamics and fatty acid metabolism. This animal model holds promise for the study of how different types of obesity and high fat diets may affect metabolism, immune phenotype, and microbial dynamics.
Highlights
Obesity is at epidemic levels, in western cultures such as the United States, where recent epidemiologic statistics indicate that 40% of American women are obese [1]
Obese pigs developed lower plasma insulin concentrations while on diet compared with lean pigs, which developed higher plasma insulin concentrations while on diet (Table 2)
When compared to lean pigs, obese pigs tended to show lower levels of IL-1β, TNF-α, IL-4, and IL-10, this varied by cycle day
Summary
Obesity is at epidemic levels, in western cultures such as the United States, where recent epidemiologic statistics indicate that 40% of American women are obese [1]. The development of insulin resistance and type II diabetes, even independent from obesity, can be predicted by an increase in inflammatory markers like interleukin 6 (IL-6) and C-reactive protein (CRP) [4, 5]. Excess adipose tissue results in increased numbers of macrophages within adipose tissue, which produce several pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and IL6 [6]. These excess cytokines establish a positive-feedback loop through their increased receptor activation, resulting in chronic inflammation
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