Journal article
Neuronal modulation of brown adipose activity through perturbation of white adipocyte lipogenesis
Molecular metabolism (Germany), Vol.16, pp.116-125
10/2018
DOI: 10.1016/j.molmet.2018.06.014
PMID: 30005879
Abstract
Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of “beige” adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT).
Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This increased sympathetic innervation could be observed at both 22 °C and 30 °C, indicating it is not a response to heat loss but rather adipocyte signaling. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed.
These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.
•Inhibition of DNL in white adipocytes increases iWAT and BAT sympathetic neuron activities.•Loss of FASN in WAT, but not BAT enhances innervation and thermogenesis in iWAT and BAT independent of thermoregulation.•Suppression of DNL in iWAT appears to trigger BAT thermogenesis through a neural link.•Although greatly increased in activity at 6 °C, DNL in BAT is dispensable to maintain euthermia.
Details
- Title: Subtitle
- Neuronal modulation of brown adipose activity through perturbation of white adipocyte lipogenesis
- Creators
- Adilson Guilherme - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USADavid J Pedersen - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USAFelipe Henriques - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USAAlexander H Bedard - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USAElizabeth Henchey - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USAMark Kelly - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USADonald A Morgan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAKamal Rahmouni - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAMichael P Czech - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA
- Resource Type
- Journal article
- Publication Details
- Molecular metabolism (Germany), Vol.16, pp.116-125
- DOI
- 10.1016/j.molmet.2018.06.014
- PMID
- 30005879
- NLM abbreviation
- Mol Metab
- ISSN
- 2212-8778
- eISSN
- 2212-8778
- Publisher
- Elsevier GmbH
- Grant note
- name: NIH, award: DK30898, DK103047
- Language
- English
- Date published
- 10/2018
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040012102771
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