A Brain-Melanocortin-Vagus Axis Mediates Adipose Tissue Expansion Independently of Energy Intake
Jenna Holland,
Joyce Sorrell,
Emily Yates,
Kathleen Smith,
Shahriar Arbabi,
Myrtha Arnold,
Marita Rivir,
Rachel Morano,
Jenny Chen,
Xiang Zhang,
Richard Dimarchi,
Stephen C. Woods,
Joan Sanchez-Gurmaches,
Eric Wohleb,
Diego Perez-Tilve
Affiliations
Jenna Holland
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Joyce Sorrell
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Emily Yates
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Kathleen Smith
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Shahriar Arbabi
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Myrtha Arnold
Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland
Marita Rivir
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Rachel Morano
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Jenny Chen
Genomics, Epigenomics and Sequencing Core, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Xiang Zhang
Genomics, Epigenomics and Sequencing Core, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Richard Dimarchi
Novo Nordisk Research Center Indianapolis, IN, USA; Department of Chemistry, Indiana University, Bloomington, IN, USA
Stephen C. Woods
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Joan Sanchez-Gurmaches
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Endocrinology and Division of Developmental Biology, Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH, USA
Eric Wohleb
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Diego Perez-Tilve
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Corresponding author
Summary: The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing sympathetic nervous system input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here, we demonstrate that reduction of brain-melanocortin signaling actively promotes fat mass gain by activating the lipogenic program and adipocyte and endothelial cell proliferation in white fat depots independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. Those vagally regulated obesogenic signals also contribute to the fat mass gain following chronic high-fat diet feeding. These data reveal a physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity. : Brain-melanocortin signaling controls fat mass indirectly by regulating energy balance and by direct control of lipid mobilization from adipose tissue via sympathetic nervous system activity. Holland et al. show that reduced brain-melanocortin signaling promotes white adipose tissue expansion via signals conveyed by efferent innervation of the vagus nerve.
