Diet-regulated production of PDGFcc by macrophages controls energy storage

Abstract

Metazoans have evolved specialized fat-storing tissues dedicated to the dynamic storage of energy. Fat tissues in mammals consist of lipid-storing adipocytes, macrophages, and stromal cells. Macrophages are tightly associated with adipocytes yet, their function in fat remains enigmatic. We report that resident, but not bone-marrow-derived, macrophages are critical for establishment and control of fat stores in metazoans. Mice lacking resident macrophages form adipocytes but fail to store lipids or to expand lipid stores in response to diet. Experiments in isolated fat-pads demonstrate that resident macrophages control fat storage via PDGFcc production in a tissue autonomous manner. Macrophage-derived PDGFfamily growth factors in Drosophila larvae similarly act on fat cells to allow storage of lipid, demonstrating evolutionary conservation. We propose that resident macrophages, similar to adipocytes, are a critical component of the adipose tissue required for its function. Furthermore, our data suggest approaches to regulate adiposity by targeting resident macrophages and PDGFcc.

Resident macrophages restrain pathological adipose tissue remodeling and protect vascular integrity in obese mice

“…A lipid receptor known as Trem2 has been identified as one of the master regulators of lipid‐associated macrophage function, helping to prevent both adipocyte hypertrophy and systemic metabolic imbalance (Jaitin et al , 2019 ). An evolutionarily conserved pathway was recently discovered in resident macrophages that control fat storage via PDGFcc secretion (preprint: Cox et al , 2020 ), which underlines their importance in maintaining the functionality of the WAT cellular microenvironment. Another study elegantly demonstrated not only the close vasculature association of ATMs and their contribution to endocytosis but also identified a clear anti‐inflammatory/detoxifying gene signature (Silva et al , 2019 ).…”

Macrophage polarization state affects lipid composition and the channeling of exogenous fatty acids into endogenous lipid pools

“…Firstly, by buffering fluctuations in tissue lipid levels, adipose tissue- and liver-resident macrophages help to maintain metabolic homeostasis ( 5 , 10 , 11 ). Moreover, it was recently demonstrated that adipose-tissue-resident macrophages (ATMs) facilitate lipid storage within white adipocytes, providing an additional means by which ATMs contribute to metabolic homeostasis ( 12 ). Secondly, increased tissue lipid levels can lead to triacylglycerol (TG) accumulation and inflammation within macrophages, thereby contributing to the development of metabolic dysfunction ( 13 , 14 ).…”

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

“…In terms of macrophage origin, the traditional view believed that bone marrow-derived mononuclear macrophages (also known as recruited macrophages) are recruited into damage tissue via chemokine (C-C motif) receptor 2 (Ccr2) in response to chemokines and inflammatory signals and affect wound healing by secreting inflammatory factors such as TNFα ( 58 ) ( 64 ). Ccr2 encodes a receptor for monocyte chemoattractant protein-1, a chemokine that specifically mediates monocyte chemotaxis, and is expressed on monocytes and macrophages, but not in microglia or tissue resident macrophage at the resting state ( 65 ).…”

“…Even scar-resident oligodendrocytes obstructed axon extension through secreted Ntm. Additionally, the traditional view is that scar-resident macrophages come from the blood supply ( 58 ) ( 64 ). But recent studies have shown that monocytes after spinal cord injury can come from adjacent skull and spine bone marrow ( 66 ).…”