Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis
Open accessAbstract
OBJECTIVE: Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. METHOD: We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). RESULTS: 2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. CONCLUSIONS: These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis.
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Increased SNS tone in WAT could be directly triggered by hypoglycemia sensing in the brain.
“This increased SNS tone in WAT could be directly triggered by hypoglycemia sensing in the brain 67, 68.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [67]
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- Authors
- Garretson, J. T., Szymanski, L. A., Schwartz, G. J., Xue, B., Ryu, V., & Bartness, T. J.
- Affiliations
- Georgia State University (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Garretson, John T.
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 5
- Issue
- 8
- Pages
- 626-634
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC5021673
- OpenAlex
- W2465919060
- Cited by
- 80
- References
- 48
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 3 · 2023: 8 · 2022: 14 · 2021: 5 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 8 · 2016: 1
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R37DK035254, DK105441-01, R01DK035254)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- white adipose tissue lipolysis, brown adipose tissue thermogenesis, sympathetic nervous system, beta3-adrenergic receptor, hormone-sensitive lipase, dorsal root ganglion neurons, 3,5-dimethylpyrazole, Siberian hamster, cold exposure
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