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Intermuscular adipose tissue in metabolic disease

Abstract

Intermuscular adipose tissue (IMAT) is a distinct adipose depot described in early reports as a ‘fatty replacement’ or ‘muscle fat infiltration’ that was linked to ageing and neuromuscular disease. Later studies quantifying IMAT with modern in vivo imaging methods (computed tomography and magnetic resonance imaging) revealed that IMAT is proportionately higher in men and women with type 2 diabetes mellitus and the metabolic syndrome than in people without these conditions and is associated with insulin resistance and poor physical function with ageing. In parallel, agricultural research has provided extensive insight into the role of IMAT and other muscle lipids in muscle (that is, meat) quality. In addition, studies using rodent models have shown that IMAT is a bona fide white adipose tissue depot capable of robust triglyceride storage and turnover. Insight into the importance of IMAT in human biology has been limited by the dearth of studies on its biological properties, that is, the quality of IMAT. However, in the past few years, investigations have begun to determine that IMAT has molecular and metabolic features that distinguish it from other adipose tissue depots. These studies will be critical to further decipher the role of IMAT in health and disease and to better understand its potential as a therapeutic target.

Key points

  • Intermuscular adipose tissue (IMAT) is a unique adipose depot that strongly associates with insulin resistance, type 2 diabetes mellitus and ageing.

  • Quantitatively, IMAT comprises a fairly small proportion of total body adipose and subcutaneous adipose tissue, although the amount of IMAT in the total body can be similar to the amount of abdominal visceral adipose tissue.

  • The molecular, cellular and other biological properties of IMAT are only beginning to be appreciated and understood.

  • IMAT has at least three distinct cellular origins.

  • Access to human IMAT samples through biopsies, combined with the latest molecular biology methods of transcriptomics, proteomics (such as single-cell or single-nuclei sequencing) and secretome (exosomes) analyses, will be critical to better understand the role of this distinct adipose tissue in human health and disease.

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Fig. 1: Micrograph depicting human IMAT in erector spinae muscle in a patient with spinal stenosis.
Fig. 2: Magnetic resonance images.
Fig. 3: Whole-body magnetic resonance imaging.
Fig. 4: Schematic with proposed mechanisms, secretome, adipokines and non-adipocyte cells that underlie the biological properties of IMAT with metabolic disease.

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Acknowledgements

The authors would like to acknowledge the contributions of David E. Kelley, M.D. (retired associate vice president cardiometabolic disease, Merck Research Laboratories, Rahway, NJ, USA), Anne B. Newman, M.D. (School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA) and Tamara B. Harris, M.D. (retired, National Institute on Aging, Bethesda, MD, USA) to the study of IMAT.

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Goodpaster, B.H., Bergman, B.C., Brennan, A.M. et al. Intermuscular adipose tissue in metabolic disease. Nat Rev Endocrinol (2022). https://doi.org/10.1038/s41574-022-00784-2

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