Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner

Ornella Parolini, M. Penza, C. Montani, A. Romani, P. Vignolini, B. Pampaloni, A. Tanini, M. L. Brandi, P. Alonso-Magdalena, A. Nadal, L. Ottobrini, E. Bignotti, S. Calza, A. Maggi, P. G. Grigolato, Diego Di Lorenzo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

149 Citazioni (Scopus)

Abstract

The soy isoflavone genistein targets adipose tissue and elicits physiological effects that may vary based on dietary intake. We hypothesized that the adipose effects of genistein are dose and gender dependent. Four-week-old C57BL/6 male and female mice received daily oral doses of genistein (50-200,000 microg/kg.d) or 17beta-estradiol (E2) (5 microg/kg.d) for 15 d or a diet containing 800 ppm genistein. Genistein increased epididymal and renal fat pad and adipocyte size at doses up to 50,000 microg/kg.d or at 800 ppm in the diet in males but not in females. The alteration in adipocity correlated with changes in peripheral insulin resistance. These treatments increased genistein serum concentrations from 35+/-6 to 103+/-26 nM 12 h after treatment and lowered plasma triglycerides and cholesterol levels. The 200,000 microg/kg.d genistein dose decreased adipose tissue weight similarly to E2. This genistein dose down-regulated estrogen receptor (beta more than alpha) and progesterone receptor expression and induced estrogen-dependent adipose differentiation factors; it did not change expression of the minimal consensus estrogen-responsive element in ERE-tK-LUC mice, which was positively modulated in other tissues (e.g. the lung). E2 down-regulated almost all examined adipogenic factors. Gene microarray analysis identified factors in fat metabolism and obesity-related phenotypes differentially regulated by low and high doses of genistein, uncovering its adipogenic and antiadipogenic actions. The lower dose induced the phospholipase A2 group 7 and the phospholipid transfer protein genes; the 200,000 microg/kg.d dose inhibited them. The antiadipogenic action of genistein and down-regulation of adipogenic genes required the expression of ERbeta. In conclusion, nutritional doses of genistein are adipogenic in a gender-specific manner, whereas pharmacological doses inhibited adipose deposition.
Lingua originaleEnglish
pagine (da-a)5740-5751
Numero di pagine12
RivistaEndocrinology
Volume147
DOI
Stato di pubblicazionePubblicato - 2006

Keywords

  • Adipocytes
  • Adipose Tissue
  • Animals
  • Body Composition
  • Body Fat Distribution
  • Cell Count
  • Cell Differentiation
  • Cell Size
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epididymis
  • Estrogen Receptor beta
  • Female
  • Gene Expression Profiling
  • Genistein
  • Kidney
  • Lipogenesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Estrogen
  • Sex Characteristics

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