Neuropathy and neural plasticity in the subcutaneous white adipose depot
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Abstract
The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.
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The decrease in nerve density was particularly evident in adipose tissue, consistent with previous reports documenting decreased adipose-tissue innervation in obesity.
“Among other tissues, this decrease was particularly evident in adipose tissue, consistent with previous reports documenting decreased adipose-tissue innervation in obesity25–27.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [25]
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- [16]Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond). 2010; 34 Suppl 1: S36– 42. Epub 2010/10/12. 10.1038/ijo.2010.182 20935665 PMC3999344 · DOI · Paper page
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- Authors
- Blaszkiewicz, M., Willows, J. W., Dubois, A. L., Waible, S., DiBello, K., Lyons, L. L., Johnson, C. P., Paradie, E., Banks, N., Motyl, K., Michael, M., Harrison, B., & Townsend, K. L.
- Affiliations
- University of Maine (US)
- Maine Medical Center Research Institute (US)
- University of New England (US)
- Corresponding author
- Townsend, Kristy L.
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-09-11
- Volume
- 14
- Issue
- 9
- Pages
- e0221766
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6738614
- OpenAlex
- W2972486514
- Cited by
- 87
- References
- 66
- Citations by year
- 2026: 16 · 2025: 14 · 2024: 13 · 2023: 12 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 5
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK114320-01A1)
- american diabetes association (1-14-JF-55)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- adipose tissue innervation, neuroplasticity, subcutaneous white adipose tissue, obesity, diabetes mellitus, aging, peripheral neuropathy, neurotrophic factors, synaptic markers, cold exposure, physical activity, metabolic dysfunction
- MeSH terms
- Aging, Animals, Cold Temperature, Diabetes Mellitus, Disease Models, Animal, Energy Metabolism, Humans, Male, Nerve Growth Factors, Neuronal Plasticity, Obesity, Peripheral Nervous System Diseases, Body Mass Index, Subcutaneous Fat, Mice, Adipose Tissue, White
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