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<p>Altered activity of brown adipose tissue (BAT) contributes to obesity, insulin resistance, and cardiovascular disease. BAT secretes endocrine factors (“batokines”) that regulate thermogenesis. We identify the serpin vaspin as a batokine that modulates adrenergic control of lipolysis and thermogenesis. Adipocyte-specific vaspin overexpression in mice reduces BAT activation and impairs thermoregulation during cold exposure or fasting. Mechanistically, vaspin binds low-density lipoprotein receptors (LRP1, LDLR, vLDLR), inhibiting adrenergic signaling and lipolysis in brown and white adipocytes by modulating phosphodiesterase activity and endocytic lipid uptake. Gene set enrichment analyses in human subcutaneous adipose tissue and in vitro studies confirm vaspin’s anti-lipolytic effects in humans. Overall, vaspin emerges as a regulatory BATokine that fine-tunes BAT thermogenic activity to limit excessive energy expenditure and preserve metabolic balance.</p>

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Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Inka Rapöhn,
  • Helen Broghammer,
  • Anne Hoffmann,
  • Kevin Möhlis,
  • Anna Moormann,
  • Isabell Kaczmarek,
  • Doreen Thor,
  • Henning Großkopf,
  • Laura Krieg,
  • Isabel Karkossa,
  • Kristin Schubert,
  • Martin von Bergen,
  • Kerstin Krause,
  • Jana Breitfeld,
  • Peter Kovacs,
  • Nora Klöting,
  • Rima Nuwayhid,
  • Stefan Langer,
  • Adhideb Ghosh,
  • Christian Wolfrum,
  • Michael Stumvoll,
  • Matthias Blüher,
  • John T. Heiker,
  • Juliane Weiner

摘要

Altered activity of brown adipose tissue (BAT) contributes to obesity, insulin resistance, and cardiovascular disease. BAT secretes endocrine factors (“batokines”) that regulate thermogenesis. We identify the serpin vaspin as a batokine that modulates adrenergic control of lipolysis and thermogenesis. Adipocyte-specific vaspin overexpression in mice reduces BAT activation and impairs thermoregulation during cold exposure or fasting. Mechanistically, vaspin binds low-density lipoprotein receptors (LRP1, LDLR, vLDLR), inhibiting adrenergic signaling and lipolysis in brown and white adipocytes by modulating phosphodiesterase activity and endocytic lipid uptake. Gene set enrichment analyses in human subcutaneous adipose tissue and in vitro studies confirm vaspin’s anti-lipolytic effects in humans. Overall, vaspin emerges as a regulatory BATokine that fine-tunes BAT thermogenic activity to limit excessive energy expenditure and preserve metabolic balance.