Elsevier

Molecular Metabolism

Volume 4, Issue 4, April 2015, Pages 337-343
Molecular Metabolism

Brief communication
Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis

https://doi.org/10.1016/j.molmet.2015.01.007Get rights and content
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open access

Abstract

Objective

Elevations in brain angiotensin-II cause increased energy expenditure and a lean phenotype. Interestingly, the metabolic effects of increased brain angiotensin-II mimic the actions of leptin, suggesting an interaction between the two systems. Here we demonstrate that angiotensin-type 1a receptors (AT1aR) in the subfornical organ (SFO), a forebrain structure emerging as an integrative metabolic center, play a key role in the body weight-reducing effects of leptin via brown adipose tissue (BAT) thermogenesis.

Methods

Cre/LoxP technology coupled with targeted viral delivery to the SFO in a mouse line bearing a conditional allele of the Agtr1a gene was utilized to determine the interaction between leptin and SFO AT1aR in metabolic regulation.

Results

Selective deletion of AT1aR in the SFO attenuated leptin-induced weight loss independent of changes in food intake or locomotor activity. This was associated with diminished leptin-induced increases in core body temperature, blunted upregulation of BAT thermogenic markers, and abolishment of leptin-mediated sympathetic activation to BAT.

Conclusions

These data identify a novel interaction between angiotensin-II and leptin in the control of BAT thermogenesis and body weight, and highlight a previously unrecognized role for the forebrain SFO in metabolic regulation.

Keywords

Leptin
Brown adipose tissue
Brain
Angiotensin
Sympathetic nervous system
Metabolic regulation

Abbreviations

Ang-II
angiotensin-II
AT1aR
angiotensin type 1a receptor
BAT
brown adipose tissue
CNS
central nervous system
LepRb
leptin receptor
OVLT
organum vasculosum lamina terminalis
RAS
renin-angiotensin system
SFO
subfornical organ
SNA
sympathetic nerve activity

Cited by (0)

6

Drs. Mark and Davisson are co-senior authors.