Diet-regulated production of PDGFcc by macrophages controls energy storage

Author:

Cox Nehemiah1ORCID,Crozet Lucile12,Holtman Inge R.3ORCID,Loyher Pierre-Louis1,Lazarov Tomi12ORCID,White Jessica B.2ORCID,Mass Elvira14ORCID,Stanley E. Richard5ORCID,Elemento Olivier67ORCID,Glass Christopher K.3ORCID,Geissmann Frederic12ORCID

Affiliation:

1. Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

2. Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.

3. Department of Cellular and Molecular Medicine, University of California, San Diego, CA, USA.

4. Developmental Biology of the Immune System, LIMES Institute, University of Bonn, 53115 Bonn, Germany.

5. Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

6. Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA.

7. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

Abstract

Macrophages: key mediators of fat storage Recent work has suggested that macrophages may regulate adiposity, but the mechanisms underlying this process remain unresolved. Cox et al. report that a macrophage-derived growth factor, Pvf3, and its receptor on fat body cells are needed for lipid storage in fruit fly larvae (see the Perspective by O'Brien and Domingos). The mouse Pvf3 ortholog, PDGFcc, was similarly required to store fat in newborn and adult mice. When PDGFcc was blocked or deleted, food intake and absorption were normal, but mice increased their energy expenditure partly due to enhanced brown adipose tissue thermogenesis. PDGFcc was produced exclusively by fat-resident macrophages rather than by those mediating inflammation and insulin resistance. This work may inform future treatments for lipodystrophy, cachexia, and obesity. Science , abe9383, this issue p. eabe9383 ; see also abj5072, p. 24

Funder

National Heart, Lung, and Blood Institute

National Cancer Institute

National Institute of Allergy and Infectious Diseases

Memorial Sloan-Kettering Cancer Center

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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