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Spop deficiency impairs adipogenesis and promotes thermogenic capacity in mice
Qinghe Li1, Yuhong Liu1, Yuanyuan Wang2
1Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, People's Republic of China.
Abstract:
As the adaptor protein that determines substrate specificity of the Cul3-SPOP-Rbx1 E3 ligase complex, SPOP is involved in numerous biological processes. However, its physiological connections with adipogenesis and thermogenesis remain poorly understood. In the current study, we report that the conditional knockout of Spop in mice results in substantial changes in protein expression, including the upregulation of a critical factor associated with thermogenesis, UCP1. Loss of SPOP also led to defects in body weight gain. In addition, conditional knockout mice exhibited resistance to high-fat-diet-induced obesity. Proteomics analysis found that proteins upregulated in the knockout mice are primarily enriched for functions in glycolysis/gluconeogenesis, oxidative phosphorylation, and thermogenesis. Furthermore, Spop knockout mice were more resilient during cold tolerance assay compared with the wild-type controls. Finally, the knockout of SPOP efficiently impaired adipogenesis in primary preadipocytes and the expression of associated genes. Collectively, these findings demonstrate the critical roles of SPOP in regulating adipogenesis and thermogenic capacity in mice.
Insights
The adaptor protein SPOP regulates fat cell development and energy expenditure. Its absence in mice improved thermogenesis and resistance to obesity, highlighting SPOP
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- SPOP acts as an adaptor protein in the Cul3-SPOP-Rbx1 E3 ligase complex, influencing various biological processes.
- The specific roles of SPOP in adipogenesis and thermogenesis are not well understood.
Purpose of the Study:
- To investigate the physiological functions of SPOP in adipogenesis and thermogenesis.
- To determine the impact of SPOP deficiency on metabolic processes in mice.
Main Methods:
- Conditional knockout of the Spop gene in mice.
- Proteomics analysis to identify differentially expressed proteins.
- Assessment of adipogenesis in primary preadipocytes.
- Evaluation of thermogenic capacity and response to high-fat diet and cold exposure.
Main Results:
- Conditional Spop knockout in mice led to altered protein expression, including increased UCP1 (thermogenesis factor).
- Spop knockout mice showed reduced body weight gain, resistance to diet-induced obesity, and enhanced cold tolerance.
- Proteomics revealed enrichment of proteins involved in glycolysis, oxidative phosphorylation, and thermogenesis in knockout mice.
- SPOP deficiency impaired adipogenesis and associated gene expression in preadipocytes.
Conclusions:
- SPOP plays a critical role in regulating adipogenesis.
- SPOP is essential for maintaining normal thermogenic capacity in mice.
- Targeting SPOP may offer therapeutic strategies for obesity and metabolic disorders.
