COP9 signalosome is required for adipose tissue maintenance and metabolic health

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Constitutive photomorphogenesis mutant 9 (COP9) signalosome (CSN) is composed of eight subunits (CSN1 through CSN8). It acts as an essential regulator of Cullin-RING-ubiquitin ligases (CRLs), which target critical cellular regulators for degradation via the ubiquitin (Ub) proteasome pathway. The role of CSN in adipose tissue development and function has not yet been studied. We sought to determine the role of CSN8, the smallest subunit of the CSN complex, in adipogenesis, adipose tissue maintenance, and metabolic balance. We first found that CSN8 level remained constant during adipogenesis and knocking down CSN8 by CRISPR/Cas9 did not impair adipocyte differentiation. Notably, mice with adipocyte-specific Csn8 gene deletion (Csn8 AKO ) showed disrupted CSN holo-complex formation and Cullin deneddylation, leading to the loss of white and brown adipose tissue. Csn8 AKO mice displayed insulin resistance while maintaining glucose tolerance. They showed increased food intake and a trend toward higher energy expenditure but were cold-intolerant. Bulk RNA sequencing revealed that CSN deficiency caused significant remodeling of white and brown adipose tissues, characterized by adipocyte death and inflammation. Specifically, white and brown adipose tissues lacking CSN8 exhibited marked upregulation of apoptotic and pyroptotic cell death, which was associated with alterations in ubiquiti

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.