Hepatic lipids promote liver metastasis

• DOI: 10.1172/jci.insight.136215
• Publication Date: 2020-09-02T15:01:28Z
• Authors: Yongjia Li; Xinming Su; Nidhi Rohatgi; Yan Zhang; Jonathan R. Brestoff; Kooresh I. Shoghi; Yalin Xu; Clay F. Semenkovich; Charles A. Harris; Lindsay L. Peterson; Katherine N. Weib...; Steven L. Teitelbaum; Wei Zou
• Keywords: Steatosis

Obesity predisposes to cancer and a virtual universality of nonalcoholic fatty liver disease (NAFLD). However, the impact hepatic steatosis on metastasis is enigmatic. We find that while control mice were relatively resistant metastasis, those which lipodystrophic or obese, with NAFLD, had dramatic increase in breast melanoma metastases. NAFLD promotes by reciprocal activation initiated tumor-induced triglyceride lipolysis juxtaposed hepatocytes. The lipolytic products are transferred cells via acid transporter protein 1, where they metabolized mitochondrial oxidation promote tumor growth. histology human indicated same occurs humans. Furthermore, comparison isolates normal established steatotic lipids enhanced tumor-stimulating capacity. Normalization glucose metabolism metformin did not reduce steatosis-induced establishing process mediated metabolic syndrome. Alternatively, eradication adipose tissue transplantation reduced mice, indicating predisposition reversible.