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Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth

Say Viengchareun1, Nathalie Servel, Bruno Fève

  • 1Inserm, U693, Le Kremlin-Bicêtre, France.

Plos One
|February 7, 2008
PubMed

Insights

Prolactin receptor signaling is crucial for brown fat development and function in newborns. Loss of this receptor impairs adipocyte differentiation and survival, highlighting its role in thermoregulation and potential as a therapeutic target.

Area of Science:

  • Endocrinology
  • Metabolism
  • Developmental Biology

Background:

  • Lactogenic hormones prolactin (PRL) and placental lactogens (PL) are vital for reproduction and mammary development.
  • These hormones signal through the prolactin receptor (PRLR), which is highly expressed in brown adipose tissue (BAT).
  • The specific impact of PRLR signaling on adipocyte function and metabolism in BAT remains largely unknown.

Purpose of the Study:

  • To investigate the role of prolactin receptor (PRLR) signaling in brown adipose tissue (BAT) differentiation and function.
  • To elucidate the molecular mechanisms by which PRLR signaling influences adipocyte development and metabolism.
  • To assess the impact of PRLR deficiency on thermoregulation and survival in newborn mice.

Main Methods:

  • Phenotypic characterization of PRLR knockout (KO) newborn mice, focusing on thermoregulation.
  • Gene expression studies of BAT differentiation markers in PRLR KO mice and derived preadipocytes.
  • Establishment and analysis of immortalized PRLR KO preadipocyte cell lines to study PRL signaling pathways.
  • Investigation of the role of Insulin-like Growth Factor-2 (IGF-2) in mediating PRLR effects.

Main Results:

  • Newborn PRLR KO mice exhibited hypotrophic BAT depots with reduced expression of key adipogenic and thermogenic genes (PPARγ2, PGC-1α, UCP1).
  • PRLR deficiency led to impaired differentiation of brown preadipocytes and decreased viability during cold exposure.
  • PRL-induced IGF-2 expression via JAK2/STAT5 signaling was identified as a key mediator, with exogenous IGF-2 rescuing differentiation defects in PRLR KO cells.

Conclusions:

  • Lactogens, in conjunction with IGF-2, are essential regulators of brown adipocyte differentiation and growth.
  • PRLR signaling is a critical factor in perinatal BAT development and thermoregulation.
  • PRLR signaling represents a potential therapeutic target for protecting newborns against hypothermia.
Abstract

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