Thumbnail
Access Restriction
Open

Author Morooka, Nobukatsu ♦ Ueguri, Kei ♦ Yee, Karen Kar Lye ♦ Yanase, Toshihiko ♦ Sato, Takashi
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ADIPOSE TISSUE ♦ ANDROGENS ♦ GENES ♦ INFLAMMATION ♦ LUCIFERASE ♦ LYMPHOKINES ♦ MACROPHAGES ♦ METABOLIC DISEASES ♦ METABOLISM ♦ MONOCYTES ♦ NECROSIS ♦ NEOPLASMS ♦ RADIOPROTECTIVE SUBSTANCES ♦ RECEPTORS ♦ TRANSCRIPTION
Abstract Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-09-02
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 477
Issue Number 4


Open content in new tab

   Open content in new tab