P1005 - EARLY-LIFE OVERNUTRITION INDUCES NF-ΚB PATHWAY ACTIVATION IN ADIPOSE TISSUE: A POTENTIAL MECHANISM FOR OBESITY PERSISTENCE

P1005

EARLY-LIFE OVERNUTRITION INDUCES NF-ΚB PATHWAY ACTIVATION IN ADIPOSE TISSUE: A POTENTIAL MECHANISM FOR OBESITY PERSISTENCE

F. Yang^1,*, Y. Zhao¹, D. Wu¹, J. Zhang¹, W. Wang¹, J. Chen ¹

¹ Child Health Care Medical Division, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, China

Rationale: Childhood obesity is a major global public health issue, with adipose tissue dysfunction playing a critical role. The NF-κB signaling pathway is implicated in obesity-associated chronic inflammation and may influence adipose metabolic function. This study aimed to explore the impact of early-life overnutrition on thermogenesis-related gene expression and NF-κB pathway activation in white adipose tissue (WAT).

Methods: Male Sprague-Dawley (SD) rats were randomly assigned to a small litter (SL, 3 pups/dam) or normal litter (NL, 10 pups/dam) group starting from postnatal day 3. Both groups were fed a standard chow diet from week 3 to week 13. Body weight was monitored weekly. At weeks 3 and 13, metabolic parameters including oxygen consumption (VO₂), carbon dioxide production (VCO₂), and heat production were measured. Ucp1 protein expression in white adipose tissue (WAT) was analyzed by Western blot, and Pgc1α mRNA expression was assessed using quantitative real-time PCR (RT-qPCR). RNA sequencing followed by pathway enrichment analysis was performed to identify differentially regulated signaling pathways.

Results: SL rats exhibited significantly higher body weight than NL rats from week 3 onward, with differences maintained through week 13 (P < 0.05). VO₂ and heat production were significantly reduced in the SL group at both time points (P < 0.05). Ucp1 and Pgc1α expression in WAT was markedly downregulated in SL rats at weeks 3 and 13. RNA-seq analysis revealed significant enrichment of the NF-κB signaling pathway in WAT from SL rats.

Conclusion: Early-life overnutrition impairs thermogenic gene expression in white adipose tissue and activates the NF-κB signaling pathway, which may contribute to persistent adipose tissue dysfunction and increased susceptibility to obesity.

Disclosure of Interest: None declared