Abstract
Bardet‐Biedl syndrome 3 gene in POMC neurons is required for glucose homeostasis
The FASEB journal, Vol.35(S1)
05/2021
DOI: 10.1096/fasebj.2021.35.S1.00216
Abstract
Bardet‐Biedl syndrome (BBS) proteins have emerged as critical regulators of various physiological functions including energy and glucose homeostasis. BBS3 protein is not part of the BBSome (a complex composed of BBS1/2/4/5/7/8/9/18), but is required for its recruitment to the cilia. Human and animals bearing disruption of various BBS genes display numerous features including obesity and diabetes, but the underlying mechanisms are not clear. Here, we investigated the role of Bbs3 gene in the anorexigenic pro‐opiomelanocortin (POMC) neurons. We crossed Bbs3fl/fl mice with POMCERCre mice. Tamoxifen was injected at 6 weeks of age for 5 days at 75 mg/kg to induce cre expression. We confirmed Cre recombinase activity in POMC neurons of POMCERCre/td‐Tomato reportermice after tamoxifen. Interestingly, both male and female POMCERCre/Bbs3fl/fl mice did not develop obesity as indicated by the lack of difference in body weight, fat mass and weight of white and brown fat pads. Insulin and glucose tolerance tests revealed that POMCERCre/Bbs3fl/fl mice have glucose intolerance, whereas insulin sensitivity was normal. In human RPE1 cells, BBS3 gene knock‐out disrupted the ciliary localization of BBS2 and BBS9 proteins, indicating a loss of BBSome‐mediated cargo trafficking to cilia. These findings demonstrate that POMC neuron BBS3, that mediate cargo transport to cilia, is not necessary for the regulation of energy homeostasis, but is involved in the regulation of glucose homeostasis.
Details
- Title: Subtitle
- Bardet‐Biedl syndrome 3 gene in POMC neurons is required for glucose homeostasis
- Creators
- Deng Guo - The University of IowaPaul Williams - The University of IowaYuying Zhao - The University of IowaMohamed Shaban - The University of IowaQihong Zhang - The University of IowaVal Sheffield - The University of IowaKamal Rahmouni - The University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.35(S1)
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2021.35.S1.00216
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 05/2021
- Academic Unit
- Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences; Neuroscience and Pharmacology; Internal Medicine; Iowa Neuroscience Institute; Medical Genetics and Genomics
- Record Identifier
- 9984071982102771
Metrics
18 Record Views