1187
Microbiota Diversity is Inversely Related to Adiposity in Mangalica Pigs
Alabama is at the epicenter of an obesity epidemic representing a critical threat to public health by precipitating increased risk to stakeholders for diabetes, heart disease, stroke, arthritis, and certain cancers. Several studies in humans and in mice have demonstrated a strong interaction between the composition and diversity of gut microbiota, inflammation, and obesity. To address the connection between these parameters, we used the Mangalica pig as a model organism given the extreme, early onset, hyperphagic obesity displayed by this breed. A growth trial was conducted where obese and lean groups were created by either allowing ad libitum access to feed or restricting energy intake to 65% of ad libitum levels. Throughout the trial longitudinal analyses of the bacterial composition of the fecal microbiota was performed using denaturing gradient gel electrophoresis (DGGE). Circulating glucose was measured in whole blood samples taken from pigs following fasting or administration of an oral glucose dose. Body composition was determined at regular intervals using ultrasound and subcutaneous adipose tissues (SC) harvested at the end of the trial to facilitate gene expression studies. As animals aged and increased in adiposity, a general reduction in the overall diversity in the gut bacteria was observed with several other changes in specific bacterial taxa as indicated by DGGE analysis. At mature weight, obese pigs exhibited 2.5-fold greater SC mass (P < 0.001) but no differences in muscle mass (P < 0.39) compared to lean counterparts. Obese pigs exhibited severe fasting hypoglycemia and impaired glucose tolerance following oral glucose challenge suggesting development of insulin resistance. The mRNA expression of interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-α) were 4.72- and 3.74-fold higher respectively in the SC of obese versus lean Mangalica as measured by real-time PCR (P < 0.01). These data provide evidence that obese Mangalica pigs indeed develop a metabolic phenotype consistent with insulin resistance and this is associated with a proinflammatory shift in gene expression in SC. Furthermore, these data suggest that obesity is inversely correlated with diversity in gut microbiota. These findings will inform the design of therapies aimed at manipulating gut microbiota and/or inflammation in the treatment of obesity.
Keywords: Microbiota, Obesity, Mangalica