Cited by 80Adipose Tissue and MetabolismLipid metabolism and biosynthesisRegulation of Appetite and Obesity

Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis

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Garretson, John T., Szymanski, Laura A., Schwartz, Gary J., Xue, Bingzhong, Ryu, Vitaly, Bartness, Timothy J.·2016·Molecular Metabolism

Abstract

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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Crossref · 10.1016/j.molmet.2016.06.013

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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.”

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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)
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
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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