Posters P450 and P201
P450
Early life dosing with Cholera Toxin B inhibits age-associated obesity in mice
Varian, Bernard1; Weber, Katherine1; Farrell, Vanessa1; Haner, Gordon1; Hardas, Alexandros2; Poutahidis, Theofilos2; Erdman, Susan1
1. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States.
2. Faculty of Veterinary Medicine, Aristotle University, Thessaloniki, Greece.
The global rise in obesity has become a concerning public health issue, associated with various inflammatory diseases including cancer and cardiovascular conditions. This study built upon the ‘Hygiene Hypothesis’ concept investigates the potential of microbial products such as cholera toxin B (CTB) as an early life vaccination strategy to prevent age-associated obesity by counteracting chronic inflammation. In order to test the hypothesis that the immune effects of CTB inhibits age associated obesity in mouse models we used 8 males and 8 females of two different genetic backgrounds of mice, CD1 outbred stock and C57BL6 inbred mice, which were susceptible to age-related weight gain. 10 µg of CTB in 0.2 mL of Phosphate Buffered Saline (PBS) or PBS sham was administered via gastric gavage 3 times every 10 days starting at 3 weeks of age until 7 weeks of age. Mice had terminal tissue collections at 6 months. In both CD1 and C57BL6 mice, early life administration of CTB resulted in a significant inhibition of age-associated obesity. Compared to control mice, CTB-treated mice displayed reduced body weight (43g to 35g in males and 36g to 30g in females, p<0.001) and abdominal fat accumulation (4.94g to 1.18g in males, p,0.001 and 18.6g to 10.27g in females, p<0.01). Histological characterization of the adipose tissue found decreased inflammatory cell accumulations, known as Crown-Like-Structures (CLS) in CTB-treated mice when compared to the control mice (18 to 1 CLS in males, P<0.0001 and 8 to 6 CLS in females, P<0.02). These results were repeated by performing adoptive cell transfer experiments in C57BL6 mice. A single cell suspension of 5×1^5 immune cells, isolated from the mesenteric lymph node of CTB-treated or control mice were injected intraperitoneally showing that the transplantation of purified immune cells were sufficient to inhibit age associated obesity, highlighting the role of host immunity in mediating CTB’s effects. Our findings demonstrate that CTB, when administered in early life, inhibits age-associated obesity in mice through immunomodulatory mechanisms. This supports the hypothesis that early life vaccination with CTB protects against developing obesity in adulthood.
P201
Jaundice and hepatic necrosis in Axolotls (Ambystoma mexicanum)
Varian, Bernard; Lee, Yao; Jordan, Ellen B; Parry, Nicola; Erdman, Susan; Garcia, Alexis
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, MA, United States.
Three of 20 white leucistic axolotls (Ambystoma mexicanum), aged 1.5 to 2.5 years, individually housed on a recirculating water system, presented with anorexia and jaundice. Gross examination revealed severe, multifocal to coalescing hepatitis, with necrosis and suspected infarction in the liver. Histopathological evaluation found hepatocellular degeneration and necrosis, variations in hepatocyte size, distinct nuclear changes (karyomegaly, binucleation, and mitotic figures), and the presence of small aggregates of basophilic intracytoplasmic material resembling inclusion bodies. To rule out infectious causes, PCR on liver was negative for ranavirus. A liver culture identified Aeromonas hydrophilia and Aeromonas caviae, which are opportunistic pathogens associated with aquatic environments. However, this was likely environmental contaminant as pathology did not identify a bacterial infection. No other overt signs of infectious etiology were observed in these cases or control cases. The housing system further reduces infectious spread as water flows from the filter system into the individual tank, back into the filter system before reaching other tanks. Water quality was suspected to be the cause of the pathology as water assessments revealed a decline in conductivity and increase in nitrates, indicating poor water quality with potential organic enrichment. These values indicate a disturbance in the water conditions, which likely provided a favorable environment for potential opportunistic pathogens to proliferate. Prompt intervention and corrective measures were implemented to address the water abnormalities, including improved filtration, adjusted feeding schedules, and water changes. The successful management of the disease outbreak was attributed to the focus on restoring optimal water quality conditions. These cases highlight the crucial role of water quality in preventing disease outbreaks in axolotls. The association between compromised water conditions, opportunistic pathogen presence, and the observed liver pathology underscores the need for maintaining optimal water quality parameters for the overall health and well-being of axolotl populations.
Bernard Varian 