The Mitochondrial Brown Adipose Tissue Maintenance Factor Nipsnap1 Interfaces Directly With the β-Oxidation Protein Machinery in Rodents

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)

Background The activation of brown adipose tissue (BAT) is associated with improved metabolic health in humans. We previously identified the mitochondrial protein Nipsnap1 as a novel regulatory factor that integrates with lipid metabolism and is critical to sustain the long-term activation of BAT, but the precise mechanism and function of Nipsnap1 are unknown. Objectives The study aims to define the function of the regulatory factor Nipsnap1 in lipid metabolism by identifying its specific protein-protein interactions and regulatory role in fatty acid β-oxidation. Methods We used adeno-associated viral (AAV) vectors to overexpress Nipsnap1 in the thermogenic adipose tissue of male C57BL/6J mice and assessed whole-body energy metabolism using metabolic cages. Mitochondrial respiration in primary brown adipocytes was measured by Seahorse assay after AAV-Nipsnap1 infection. To further investigate molecular mechanisms, an immunoprecipitation assay was performed to identify Nipsnap1-interacting proteins. Results We showed that adipose-specific overexpression of Nipsnap1 in mice elicits a 20% increase in energy expenditure through the utilization of lipids as an energy substrate as evidenced by the shift of the respiratory exchange ratio to 0.7 (P Conclusions This study elucidates a mechanistic function of Nipsnap1 in thermogenic fat where Nipsnap1 facilitates a functional connection

Evidence level

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

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