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Hepatic lipids promote liver metastasis
Yongjia Li, … , Steven L. Teitelbaum, Wei Zou
Yongjia Li, … , Steven L. Teitelbaum, Wei Zou
Published September 3, 2020
Citation Information: JCI Insight. 2020;5(17):e136215. https://doi.org/10.1172/jci.insight.136215.
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Research Article Hepatology Oncology

Hepatic lipids promote liver metastasis

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Abstract

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

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. Weilbaecher, Steven L. Teitelbaum, Wei Zou

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Figure 5

Steatosis promotes tumor growth.

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Steatosis promotes tumor growth.
(A) Morphology of Bo1 cells cultured wi...
(A) Morphology of Bo1 cells cultured with Con or steatotic liver of FF mice in serum-free medium; left panel shows the normal Bo1 cells cultured with medium with 10% serum. Scale bar: 100 μm. (B and C) Bo1 cells were injected directly into livers of 2-month-old FF and control mice. Tumor burden was analyzed 8 days later: (B) in vivo BLI image and (C) quantification of tumor burden in liver. n = 3–5. (D) PCNA immunostaining of liver of control or FF mice 12 days after intracardiac injection of Bo1 cells. n = 3. Data are presented as mean ± SD. *P < 0.05, as determined by unpaired 2-tailed t test (C).

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