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

CN Young, DA Morgan, SD Butler, K Rahmouni… - Molecular …, 2015 - Elsevier
CN Young, DA Morgan, SD Butler, K Rahmouni, SB Gurley, TM Coffman, AL Mark…
Molecular metabolism, 2015Elsevier
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 (AT 1a R) 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 …
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.
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