PP388 - OTOPETRIN 1 PROTECTS AGAINST ADIPOSE TISSUE WASTING DURING CANCER CACHEXIA PROGRESSION

PP388

OTOPETRIN 1 PROTECTS AGAINST ADIPOSE TISSUE WASTING DURING CANCER CACHEXIA PROGRESSION

N. Chen¹, D. Li², X. Yan³, W. Zhai³, C. He³, Z. Li³, D. Huang¹, X. Shen^3,*

¹NHC Key Laboratory of Clinical Nutrition and Intervention, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ²Shanghai Jiao Tong University School of Medicine, Shanghai, ³The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Rationale: Cancer cachexia involves progressive white adipose tissue (WAT) wasting, but key regulators driving this process remain unclear. Identifying such regulators may reveal therapeutic targets.

Methods: Transcriptomic analysis of WAT from Lewis lung carcinoma (LLC) tumor-bearing mice (pre-cachexia and cachexia models) identified OTOP1. Human subcutaneous WAT OTOP1 expression was measured in cancer patients (with/without cachexia) and correlated with BMI, albumin, and hemoglobin. In adipocytes treated with tumor-conditioned medium, OTOP1 was overexpressed, with or without a PPARγ antagonist; lipolysis, adipogenesis, NF-κB, and PPARγ signaling were assessed. OTOP1 was overexpressed in adipose tissue of LLC tumor-bearing mice to evaluate tissue wasting and lipid metabolism.

Results: OTOP1 expression was markedly reduced in cachectic patients and correlated positively with BMI, albumin, and hemoglobin. OTOP1 overexpression in adipocytes suppressed NF-κB signaling, activated PPARγ, reduced lipolysis, and enhanced adipogenesis; these effects were partially reversed by a PPARγ antagonist. In vivo, OTOP1 overexpression alleviated adipose tissue wasting and improved lipid metabolism in LLC tumor-bearing mice.

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Conclusion: OTOP1 protects against adipose wasting in cancer cachexia by modulating NF-κB and PPARγ pathways, suggesting a potential target for intervention.

Disclosure of Interest: None declared