Journal article
BBSome ablation in SF1 neurons causes obesity without comorbidities
Molecular metabolism (Germany), Vol.48, pp.101211-101211
06/2021
DOI: 10.1016/j.molmet.2021.101211
PMID: 33722691
Abstract
The hypothalamic ventromedial nucleus (VMH) plays a major role in metabolic control, but the molecular mechanisms involved remain poorly defined. We analyzed the relevance of the BBSome, a protein complex composed of 8 Bardet–Biedl syndrome (BBS) proteins including BBS1, in VMH steroidogenic factor 1 (SF1) neurons for the control of energy homeostasis and related physiological processes.
We generated mice bearing selective BBSome disruption, through Bbs1 gene deletion, in SF1 neurons (SF1Cre/Bbs1fl/fl). We analyzed the consequence on body weight, glucose homeostasis, and cardiovascular autonomic function of BBSome loss in SF1 neurons.
SF1Cre/Bbs1fl/fl mice had increased body weight and adiposity under normal chow conditions. Food intake, energy absorption, and digestive efficiency were not altered by Bbs1 gene deletion in SF1 neurons. SF1Cre/Bbs1fl/fl mice exhibited lower energy expenditure, particularly during the dark cycle. Consistent with this finding, SF1Cre/Bbs1fl/fl mice displayed reduced sympathetic nerve traffic and expression of markers of thermogenesis in brown adipose tissue. SF1Cre/Bbs1fl/fl mice also had lower sympathetic nerve activity to subcutaneous white adipose tissue that was associated with a protein expression profile that promotes lipid accumulation. Notably, despite obesity and hyperinsulinemia, SF1Cre/Bbs1fl/fl mice did not exhibit significant changes in glucose metabolism, insulin sensitivity, blood pressure, and baroreflex sensitivity.
Our findings demonstrate that the SF1 neuron BBSome is necessary for the regulation of energy homeostasis through modulation of the activity of the sympathetic nervous system and that the SF1 neuron BBSome is required for the development of obesity-related comorbidities.
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•Disruption of the BBSome in SF1 neurons increases body weight and adiposity.•Loss of the BBSome in SF1 neurons decreases energy expenditure without altering energy intake.•Absence of the BBSome in SF1 neurons interfere with the activity of brown and white adipose tissues.•Absence of the BBSome in SF1 neurons protect from obesity-related conditions.
Details
- Title: Subtitle
- BBSome ablation in SF1 neurons causes obesity without comorbidities
- Creators
- Mohamed Rouabhi - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USADeng-Fu Guo - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USADonald A Morgan - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USAZhiyong Zhu - Veterans Affairs Health Care System, Iowa City, IA, USAMiguel López - NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, SpainLeonid Zingman - Veterans Affairs Health Care System, Iowa City, IA, USAJustin L Grobe - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USAKamal Rahmouni - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Molecular metabolism (Germany), Vol.48, pp.101211-101211
- DOI
- 10.1016/j.molmet.2021.101211
- PMID
- 33722691
- NLM abbreviation
- Mol Metab
- ISSN
- 2212-8778
- eISSN
- 2212-8778
- Publisher
- Elsevier GmbH
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health
- Language
- English
- Date published
- 06/2021
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070223102771
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