Hepatocellular carcinoma induced by hepatocyte Pten deletion reduces BAT UCP-1 and thermogenic capacity in mice, despite increasing serum FGF-21 and iWAT browning.

Autor: Peixoto ÁS; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Moreno MF; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Castro É; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Perandini LA; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Belchior T; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Oliveira TE; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Vieira TS; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Gilio GR; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Tomazelli CA; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Leonardi BF; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Ortiz-Silva M; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Silva Junior LP; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil., Moretti EH; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Steiner AA; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Festuccia WT; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508000, Sao Paulo, Brazil. william.festuccia@usp.br.
Jazyk: angličtina
Zdroj: Journal of physiology and biochemistry [J Physiol Biochem] 2023 Nov; Vol. 79 (4), pp. 731-743. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1007/s13105-023-00970-4
Abstrakt: Hepatocellular carcinoma (HCC) markedly enhances liver secretion of fibroblast growth factor 21 (FGF-21), a hepatokine that increases brown and subcutaneous inguinal white adipose tissues (BAT and iWAT, respectively) uncoupling protein 1 (UCP-1) content, thermogenesis and energy expenditure. Herein, we tested the hypothesis that an enhanced BAT and iWAT UCP-1-mediated thermogenesis induced by high levels of FGF-21 is involved in HCC-associated catabolic state and fat mass reduction. For this, we evaluated body weight and composition, liver mass and morphology, serum and tissue levels of FGF-21, BAT and iWAT UCP-1 content, and thermogenic capacity in mice with Pten deletion in hepatocytes that display a well-defined progression from steatosis to steatohepatitis (NASH) and HCC upon aging. Hepatocyte Pten deficiency promoted a progressive increase in liver lipid deposition, mass, and inflammation, culminating with NASH at 24 weeks and hepatomegaly and HCC at 48 weeks of age. NASH and HCC were associated with elevated liver and serum FGF-21 content and iWAT UCP-1 expression (browning), but reduced serum insulin, leptin, and adiponectin levels and BAT UCP-1 content and expression of sympathetically regulated gene glycerol kinase (GyK), lipoprotein lipase (LPL), and fatty acid transporter protein 1 (FATP-1), which altogether resulted in an impaired whole-body thermogenic capacity in response to CL-316,243. In conclusion, FGF-21 pro-thermogenic actions in BAT are context-dependent, not occurring in NASH and HCC, and UCP-1-mediated thermogenesis is not a major energy-expending process involved in the catabolic state associated with HCC induced by Pten deletion in hepatocytes.
(© 2023. The Author(s) under exclusive licence to University of Navarra.)
Databáze: MEDLINE
Externí odkaz: