Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo
Abstract
Abstract 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.
Article Details
Authors (24)
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
Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH—Helmholtz-Zentrum für Umweltforschung
Kerstin Krause
Jana Breitfeld
Division of Endocrinology, Nephrology and Rheumatology, Department of Medicine III, Leipzig University
Peter Kovacs
Division of Endocrinology, Nephrology and Rheumatology, Department of Medicine III, Leipzig University
Nora Klöting
Rima Nuwayhid
Stefan Langer
Adhideb Ghosh
Christian Wolfrum
Michael Stumvoll
Matthias Blüher
John T. Heiker
Juliane Weiner