Journal article
Metabolic Consequences of Skeletal Muscle- and Liver-Specific BBSome Deficiency
American journal of physiology: endocrinology and metabolism, Vol.325(6), pp.E711-E722
12/01/2023
DOI: 10.1152/ajpendo.00174.2023
PMCID: PMC10864019
PMID: 37909854
Abstract
The BBSome is a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins including BBS1. Humans and mice lacking a functional BBSome display obesity and type 2 diabetes, highlighting the importance of this protein complex for metabolic regulation. However, the contribution of the BBSome in insulin sensitive tissues such as skeletal muscle and liver to metabolic regulation is ill defined. Here, we show that disruption of the BBSome through Bbs1 gene deletion in the skeletal muscle had no effect on body weight, glucose handling, but improved insulin sensitivity of female mice without changing insulin receptor signaling. Interestingly, when fed an obesogenic diet, male mice lacking the Bbs1 gene in skeletal muscle exhibited heightened insulin sensitivity despite the comparable weight gain and glucose tolerance relative to controls. On the other hand, normal chow-fed mice missing the Bbs1 gene in hepatocytes displayed increased body weight, as well as impaired glucose handling and insulin sensitivity. This was associated with attenuated insulin signaling in liver and hepatocytes, but not skeletal muscle and white adipose tissue. Moreover, hepatocytes lacking the Bbs1 gene displayed significant reduction in plasma membrane insulin receptor levels due to the mitochondrial dysfunction evoked by loss of the BBSome. Together, these findings demonstrate that myocyte BBSome is minimally involved in metabolic regulation whereas the hepatic BBSome plays a critical role in the control of energy homeostasis and insulin sensitivity through its requirement for insulin receptor trafficking.
Details
- Title: Subtitle
- Metabolic Consequences of Skeletal Muscle- and Liver-Specific BBSome Deficiency
- Creators
- Younes Rouabhi - University of IowaDeng-Fu Guo - University of IowaYuying Zhao - University of IowaKamal Rahmouni - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.325(6), pp.E711-E722
- DOI
- 10.1152/ajpendo.00174.2023
- PMID
- 37909854
- PMCID
- PMC10864019
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- ISSN
- 0193-1849
- eISSN
- 1522-1555
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa, award: Fraternal Order of Eagles Diabetes Research Center; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: HL084207 and HL162773; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: BX004249 and BX006040
- Language
- English
- Electronic publication date
- 11/01/2023
- Date published
- 12/01/2023
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984505159202771
Metrics
5 Record Views