Session: 747 APS Neural Control of Glucose and Energy Homeostasis: Implications for Diabetes and Obesity Poster Session
(747.2) Conditional Disruption of the BBSome in POMC Neurons Alter Energy and Glucose Homeostasis
Monday, April 4, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E391
Deng Guo (The University of Iowa, The University of Iowa), Paul Williams (The University of Iowa), Kamal Rahmouni (The University of Iowa, The University of Iowa, The University of Iowa)
Presenting Author The University of Iowa, The University of Iowa Iowa City, Iowa
The BBSome, a protein complex composed of 8 Bardet-Biedl syndrome (BBS) proteins including BBS1 has emerged as critical regulator of energy and glucose homeostasis. Humans and animals bearing disruption of the BBSome through loss of various BBS genes display numerous features including obesity and diabetes, but the underlying mechanisms are not well understood. We previously demonstrated that BBSome deficiency in the anorexigenic proopiomelanocortin (POMC) neurons through deletion of the Bbs1 gene lead to the development of obesity. To determine the effects BBSome deficiency in adulthood, we bred mice expressing an inducible POMCERCre with Bbs1fl/fl mice. tdTomato reporter mice were further breed with these mice to validate Cre recombinase via red tdTomato fluorescence protein expression. To induce Bbs1 gene deletion we treated the POMCERCre/Bbs1fl/fl at age of 6 weeks with tamoxifen (75 mg/kg, IP, for 5 days). Importantly, both male and female POMCERCre/Bbs1fl/fl mice displayed an obesity phenotype as indicated by the increased (Plt;0.05) body weight (41.0±1.3 vs 36.0±1.9 g in males and 29.0±1.1 vs 26.3±0.9 g in females at age of 20 weeks) and fat mass (10.8±1.2 vs. 7.8.±1.7g in males and 8.2±1.4 vs. 4.8±0.9 g in females). This was associated with increased (Plt;0.05) food intake (3.3.±0.3 vs. 2.9±0.2 g in males and 2.8±0.4g vs 2.5±0.2 g in females). These results indicate that hyperphagia contributes to the development of obesity in POMCERCre/Bbs1fl/fl mice. Moreover, using glucose tolerance and insulin tolerance tests we found that both male and female POMCERCre/Bbs1fl/fl mice display glucose intolerance and insulin resistance. These findings demonstrate the importance of the BBSome in POMC neurons for the regulation of energy and glucose homeostasis.
