Peixoto 2023 J Physiol Biochem

Peixoto ÁS, Moreno MF, Castro É, Perandini LA, Belchior T, Oliveira TE, Vieira TS, Gilio GR, Tomazelli CA, Leonardi BF, Ortiz-Silva M, Silva Junior LP, Moretti EH, Steiner AA, Festuccia WT (2023) Hepatocellular carcinoma induced by hepatocyte Pten deletion reduces BAT UCP-1 and thermogenic capacity in mice, despite increasing serum FGF-21 and iWAT browning. https://doi.org/10.1007/s13105-023-00970-4

» J Physiol Biochem 79:731-43. PMID: 37405670 Open Access

Peixoto Albert S, Moreno Mayara F, Castro Erique, Perandini Luiz A, Belchior Thiago, Oliveira Tiago E, Vieira Thayna S, Gilio Gustavo R, Tomazelli Caroline A, Leonardi Bianca F, Ortiz-Silva Milene, Silva Junior Luciano P, Moretti Eduardo H, Steiner Alexandre A, Festuccia William T (2023) J Physiol Biochem

Abstract: 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. • Keywords: Brown adipose tissue, Energy expenditure, Nonalcoholic fatty liver disease, Thermogenic capacity, UCP-1, White adipose tissue browning • Bioblast editor: Plangger M • O2k-Network Lab: BR Sao Paulo Festuccia W

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Liver, Fat 

HRR: Oxygraph-2k 

2023-07, Labelling