Editors' ChoiceMetabolism

Anxious to lose weight

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Science Translational Medicine  20 Feb 2019:
Vol. 11, Issue 480, eaaw5329
DOI: 10.1126/scitranslmed.aaw5329

Abstract

Anxiety leads to increased whole-body energy expenditure and thermogenesis in mice, preventing weight gain upon high-fat diet feeding.

Anxiety is a state of fear and apprehension about what is to come. Occasional and transient anxiety is a natural response to potential threats, but prolonged anxiety can be debilitating and lead to body weight alteration. Although some patients suffering from anxiety disorders gain weight, many suffer from sudden weight loss. The mechanisms mediating these effects are unclear.

To solve this conundrum, Xie and colleagues explored metabolic changes in a mouse model of anxiety induced by ablation of brain-derived neurotrophic factor (BDNF) from the cortex, hippocampus, and some parts of the amygdala. Mice lacking BDNF ate more than their control littermates, yet they did not gain more weight. On the contrary, when fed with a high-fat diet, mice lacking BDNF resisted the increase in body weight observed in controls. This effect was associated with a rapid increase in energy expenditure and body temperature, due to brown adipose tissue activation. Moreover, BDNF knockout mice showed improved regulation of blood glucose.

Using a series of cell-specific BDNF deletion models, BDNF re-expression studies, as well as transneuronal tracing, the authors found that BDNF deletion specifically in the amygdala partially mimicked the metabolic phenotype observed in animals with BDNF deletion in several brain areas. Lastly, pharmacological induction of anxiety rapidly increased energy expenditure

Establishing a link between anxiety and increased metabolic activity in humans will require additional investigation. Similarly, why some individuals with anxiety lose weight while others gain it is a question that remains unexplored. Nevertheless, the link between psychiatric disorders and systemic metabolism is intriguing and has important implications for our understanding of body weight management and guidance of patients undergoing therapy for anxiety disorders.

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