IFN-alpha induces apoptosis of adipose tissue cells.
Interferon alpha (IFN-alpha) is produced in response to viral infections and used clinically in the therapy of a variety of cancers and viral infections. IFN-alpha treatment is often associated with severe weight reduction. To elucidate the mechanism of IFN-associated weight loss, we studied its effect on adipocytes in vitro and in vivo. Diet-induced obese (DIO) C57BL/6 mice were treated continuously for 8 days with human IFN-alpha A/D (100 U/g body weight) or with vehicle alone. The body weight and adipose cell size of IFN-alpha A/D-treated DIO mice were significantly lower (P<0.05 and P<0.001, respectively) as compared with those of control DIO mice. PI3K and Bcl-2 were down-regulated whereas Bax expression was elevated in adipose tissue following IFN treatment as compared to adipose tissue of control DIO mice. Treatment of differentiated 3T3-F442A adipocytes with IFN-alpha A/D (250 U/ml, 36 h) significantly increased the number of apoptotic cells from 15.8% in control cells to 56+/-6%. In conclusion, weight loss following IFN-alpha therapy is due at least in part to increased apoptosis of adipocytes.
Birk
Ruth Z
RZ
National Institute of Biotechnology, Ben-Gurion University, Beer-Sheba 84105, Israel. rbirk@bgu.ac.il
Rubinstein
Menachem
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects*; D058534:Class I Phosphatidylinositol 3-Kinases; D015536:Down-Regulation; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D058534:Class I Phosphatidylinositol 3-Kinases; D016898:Interferon-alpha; D019869:Phosphatidylinositol 3-Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C421683:Pik3cd protein, mouse