Activation of Anxiogenic Circuits Instigates Resistance to Diet-Induced Obesity via Increased Energy Expenditure

Highlights

• Deletion of the Bdnf gene in Emx1-expressing neurons of the brain leads to leanness

• The Bdnf mutant displays elevated anxiety and impaired GABAergic transmission

• The leanness of the mutant is due to increased basal metabolism and thermogenesis

• Amygdalar BDNF re-expression reverses anxiety and metabolic phenotypes of the mutant

Summary

Anxiety disorders are associated with body weight changes in humans. However, the mechanisms underlying anxiety-induced weight changes remain poorly understood. Using Emx1^Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some amygdalar subregions. The resulting mutant mice displayed impaired GABAergic transmission and elevated anxiety. They were leaner when fed either a chow diet or a high-fat diet, owing to higher sympathetic activity, basal metabolic rate, brown adipocyte thermogenesis, and beige adipocyte formation, compared to control mice. BDNF re-expression in the amygdala rescued the anxiety and metabolic phenotypes in mutant mice. Conversely, anxiety induced by amygdala-specific Bdnf deletion or administration of an inverse GABA_A receptor agonist increased energy expenditure. These results reveal that increased activities in anxiogenic circuits can reduce body weight by promoting adaptive thermogenesis and basal metabolism via the sympathetic nervous system and suggest that amygdalar GABAergic neurons are a link between anxiety and metabolic dysfunction.