University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Cardiovascular Medicine; UMass Metabolic Network

Publication Date

3-1-2016

Document Type

Article

Disciplines

Cardiovascular Diseases | Cell Biology | Cellular and Molecular Physiology

Abstract

The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion and destabilization. Despite these facts, there is an accumulating body of evidence that macrophages also have beneficial functions in both atherosclerosis and visceral obesity. Potentially beneficial functions that are common to these different contexts include the regulation of efferocytosis, lipid buffering, and anti-inflammatory effects. Autophagy, the process by which cytoplasmic contents are delivered to the lysosome for degradation, is integral to many of these protective biologic functions. The macrophage utilizes autophagy as a molecular tool to maintain tissue integrity and homeostasis at baseline (e.g., bone growth) and in the face of ongoing metabolic insults (e.g., fasting, hypercholesterolemia, obesity). Herein, we highlight recent evidence demonstrating that abrogation of certain macrophage functions, in particular autophagy, exacerbates both atherosclerosis and obesity-induced insulin resistance. Insulin signaling through mammalian target of rapamycin (mTOR) is a crucial regulatory node that links nutrient availability to macrophage autophagic flux. A more precise understanding of the metabolic substrates and triggers for macrophage autophagy may allow therapeutic manipulation of this pathway. These observations underscore the complexity of the field "immunometabolism", validate its importance, and raise many fascinating and important questions for future study.

Keywords

Atherosclerosis, Autophagy, Cholesterol, Insulin resistance, Macrophage, Visceral adipose, mTOR

Rights and Permissions

Citation: J Mol Med (Berl). 2016 Mar;94(3):267-75. doi: 10.1007/s00109-016-1385-4. Epub 2016 Feb 4. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of molecular medicine (Berlin, Germany)

PubMed ID

26847458

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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