Abstract
Brainstem BBSome Regulates Glucose Metabolism and High Fat Diet Sensitivity
The FASEB journal, Vol.36(S1), p.n/a
05/2022
DOI: 10.1096/fasebj.2022.36.S1.R3611
Abstract
Bardet‐Biedl syndrome (BBS) proteins form a protein trafficking complex (BBSome) that regulates the composition of membrane proteins and contributes to neuron function. Patients harboring mutations in any BBS gene results in BBSome dysfunction and the development of metabolic complications including obesity and type 2 diabetes. Studies from our lab and others indicate that hypothalamic BBSome is a critical regulator of metabolic homeostasis, however the role of the BBSome in the brainstem is unknown. To determine whether hindbrain BBSome contributes to metabolic regulation, we crossed Phox2bCre mice with BBS1fl/fl mice (Phox2bCre/BBS1fl/fl) yielding BBS1 deletion specifically in brainstem nuclei. BBS1 deletion exclusively in hindbrain nuclei was validated by breeding these mice on a tdTomato Cre reporter background. Male Phox2bCre/BBS1fl/fl mice maintained on standard chow diet did not exhibit energy imbalance as evident by comparable body weight (37.2±2.8g vs. 35.8±4.4g), body composition (fat 20.8±2.8% vs 15.6±4.1%, lean 60.6±2.5% vs 64.2±3.0%), and food intake (3.5±0.4g/day vs 3.8±0.5g/day) relative to litter‐mate controls at 20 weeks of age. Interestingly, hindbrain BBSome disruption impairs glucose clearance and induces insulin resistance suggested by glucose (AUC 36,323±3027 vs 26,129±1972) and insulin (AUC 11,749±1678 vs 7,737±1559) tolerance tests. Strikingly, Phox2bCre/BBS1fl/fl male mice exhibit resistance to diet‐induced obesity indicated by decreased body weight (45.0±1.8g vs. 54.1±1.3g) when maintained on a high fat/high sugar diet independent of body composition (fat 42.5±1.6% vs 40.1±2.1%, lean 45.5±0.7 vs 48.4±1.5%) and food consumption (2.7±0.2g/day vs 3.0±0.1g/day). Both Phox2bCre/BBS1fl/fl and littermate controls developed diabetes when exposed to an obesogenic diet as indicated by glucose (AUC 63,645±4438 vs 62,477±2654) and insulin (AUC 14,303±3446 vs 16,406±2160) tolerance tests. These findings suggest that brainstem BBSome critically regulates glucose metabolism, but not energy balance, in mice maintained on a standard diet regimen. Furthermore, our studies indicate that hindbrain BBSome contributes to the development of diet‐induced obesity without effecting glucose handling and food intake.
Details
- Title: Subtitle
- Brainstem BBSome Regulates Glucose Metabolism and High Fat Diet Sensitivity
- Creators
- Connor Laule - University of IowaDeng Guo - University of IowaKamal Rahmouni - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.36(S1), p.n/a
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2022.36.S1.R3611
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- NIH
- Language
- English
- Date published
- 05/2022
- Academic Unit
- Neuroscience and Pharmacology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984230623302771
Metrics
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