Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor γ1 (PPARγ1) overexpression

被引:534
作者
Yu, ST
Matsusue, K
Kashireddy, P
Cao, WQ
Yeldandi, V
Yeldandi, AV
Rao, MS
Gonzalez, FJ
Reddy, JK
机构
[1] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA
[2] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1074/jbc.M210062200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peroxisome proliferator activated-receptor (PPAR) isoforms, alpha and gamma, function as important coregulators of energy (lipid) homeostasis. PPARalpha regulates fatty acid oxidation primarily in liver and to a lesser extent in adipose tissue, whereas PPARgamma serves as a key regulator of adipocyte differentiation and lipid storage. Of the two PPARgamma isoforms, PPARgamma1 and PPARgamma2 generated by alternative splicing, PPARgamma1 isoform is expressed in liver and other tissues, whereas PPARgamma2 isoform is expressed exclusively in adipose tissue where it regulates adipogenesis and lipogenesis. Since the function of PPARgamma1 in liver is not clear, we have, in this study, investigated the biological impact of overexpression of PPARgamma1 in mouse liver. Adenovirus-PPARgamma1 injected into the tail vein induced hepatic steatosis in PPARalpha(-/-) mice. Northern blotting and gene expression profiling results showed that adipocyte-specific genes and lipogenesis-related genes are highly induced in PPARalpha(-/-) livers with PPARgamma1 overexpression. These include adipsin, adiponectin, aP2, caveolin-1, fasting-induced adipose factor, fat-specific gene 27 (FSP27), CD36, Delta(9) desaturase, and malic enzyme among others, implying adipogenic transformation of hepatocytes. Of interest is that hepatic steatosis per se, induced either by feeding a diet deficient in choline or developing in fasted PPARalpha(-/-) mice, failed to induce the expression of these PPARgamma-regulated adipogenesis-related genes in steatotic liver. These results suggest that a high level of PPARgamma1 in mouse liver is sufficient for the induction of adipogenic transformation of hepatocytes with adipose tissue-specific gene expression and lipid accumulation. We conclude that excess PPARgamma activity can lead to the development of a novel type of adipogenic hepatic steatosis.
引用
收藏
页码:498 / 505
页数:8
相关论文
共 61 条
  • [11] Peroxisome proliferator-activated receptors: Nuclear control of metabolism
    Desvergne, B
    Wahli, W
    [J]. ENDOCRINE REVIEWS, 1999, 20 (05) : 649 - 688
  • [12] FAN JY, 1983, J CELL SCI, V61, P219
  • [13] Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta
    Forman, BM
    Chen, J
    Evans, RM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) : 4312 - 4317
  • [14] Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis
    Ge, K
    Guermah, M
    Yuan, CX
    Ito, M
    Wallberg, AE
    Spiegelman, BM
    Roeder, RG
    [J]. NATURE, 2002, 417 (6888) : 563 - 567
  • [15] Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferator-activated receptor-γ agonists
    Gerhold, DL
    Liu, F
    Jiang, G
    Li, Z
    Xu, J
    Lu, M
    Sachs, JR
    Bagchi, A
    Fridman, A
    Holder, DJ
    Doebber, TW
    Berger, J
    Elbrecht, A
    Moller, DE
    Zhang, BB
    [J]. ENDOCRINOLOGY, 2002, 143 (06) : 2106 - 2118
  • [16] A role for C/EBPβ in regulating peroxisome proliferator-activated receptor γ activity during adipogenesis in 3T3-L1 preadipocytes
    Hamm, JK
    Park, BH
    Farmer, SR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (21) : 18464 - 18471
  • [17] Peroxisomal and mitochondrial fatty acid β-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor α and peroxisomal fatty Acyl-CoA oxidase -: Genotype correlation with fatty liver phenotype
    Hashimoto, T
    Fujita, T
    Usuda, N
    Cook, W
    Qi, C
    Peters, JM
    Gonzalez, FJ
    Yeldandi, AV
    Rao, MS
    Reddy, JK
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (27) : 19228 - 19236
  • [18] Defect in peroxisome proliferator-activated receptor α-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting
    Hashimoto, T
    Cook, WS
    Qi, C
    Yeldandi, AV
    Reddy, JK
    Rao, MS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) : 28918 - 28928
  • [19] A GENE INDUCIBLE BY SERUM GROWTH-FACTORS ENCODES A MEMBER OF THE STEROID AND THYROID-HORMONE RECEPTOR SUPERFAMILY
    HAZEL, TG
    NATHANS, D
    LAU, LF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (22) : 8444 - 8448
  • [20] AdipoQ is a novel adipose-specific gene dysregulated in obesity
    Hu, E
    Liang, P
    Spiegelman, BM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (18) : 10697 - 10703