Dataset Information

Sensory neurons expressing calcitonin gene-related peptide ? regulate adaptive thermogenesis and diet-induced obesity.

ABSTRACT:

Objectives

Heat-sensory neurons from the dorsal root ganglia (DRG) play a pivotal role in detecting the cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis remains elusive. It is also unknown whether these neurons play a role in obesity and energy metabolism.

Methods

We used genetic ablation of heat-sensing neurons expressing calcitonin gene-related peptide ? (CGRP?) to assess whole-body energy expenditure, weight gain, glucose tolerance, and insulin sensitivity in normal chow and high-fat diet-fed mice. Exvivo lipolysis and transcriptional characterization were combined with adipose tissue-clearing methods to visualize and probe the role of sensory nerves in adipose tissue. Adaptive thermogenesis was explored using infrared imaging of intrascapular brown adipose tissue (iBAT), tail, and core temperature upon various stimuli including diet, external temperature, and the cooling agent icilin.

Results

In this report, we show that genetic ablation of heat-sensing CGRP? neurons promotes resistance to weight gain upon high-fat diet (HFD) feeding and increases energy expenditure in mice. Mechanistically, we found that loss of CGRP?-expressing sensory neurons was associated with reduced lipid deposition in adipose tissue, enhanced expression of fatty acid oxidation genes, higher exvivo lipolysis in primary white adipocytes, and increased mitochondrial respiration from iBAT. Remarkably, mice lacking CGRP? sensory neurons manifested increased tail cutaneous vasoconstriction at room temperature. This exacerbated cold perception was not associated with reduced core temperature, suggesting that heat production and heat conservation mechanisms were engaged. Specific denervation of CGRP? neurons in intrascapular BAT did not contribute to the increased metabolic rate observed upon global sensory denervation.

Conclusions

Taken together, these findings highlight an important role of cutaneous thermoreceptors in regulating energy metabolism by triggering counter-regulatory responses involving energy dissipation processes including lipid fuel utilization and cutaneous vasodilation.

SUBMITTER: Makwana K

PROVIDER: S-EPMC7820934 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Sensory neurons expressing calcitonin gene-related peptide α regulate adaptive thermogenesis and diet-induced obesity.

Makwana Kuldeep K Chodavarapu Harshita H Morones Nancy N Chi Jingyi J Barr William W Novinbakht Edward E Wang Yidan Y Nguyen Peter Tuan PT Jovanovic Predrag P Cohen Paul P Riera Celine E CE

Molecular metabolism 20210105

<h4>Objectives</h4>Heat-sensory neurons from the dorsal root ganglia (DRG) play a pivotal role in detecting the cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis remains elusive. It is also unknown whether these neurons play a role in obesity and energy metabolism.<h4>Methods</h4>We used genetic ablation of heat-sensing neurons expressing calcito ...[more]

PMID: 33412345

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