AsianScientist (Nov. 11, 2014) – Scientists have identified the molecule that links exercise to improved symptoms of depression—a hormone secreted by fat cells known as adiponectin. These results have been published in the Proceedings of the National Academy of Sciences.
Depressive disorders affect an estimated 121 million people around the world. While antidepressant medication is currently the first line of treatment, interventions such as exercise therapy are increasingly recognized as helpful.
Clinical studies have shown that patients with depression have lower plasma levels of adiponectin, which increase in response to antidepressant treatment. However, whether adiponectin acts directly on the brain and its mechanisms of action remain unknown.
In the present study led by Professor So Kwok-Fai from the University of Hong Kong, a team of researchers has identified a previously unknown role for adiponectin, a hormone involved in the regulation of glucose levels and fatty acid breakdown.
Firstly, they showed that adiponectin injected into the bloodstream of mice was able to cross the blood-brain barrier. Once there, adiponectin correlated with an increase in the number of hippocampal neurons and reduced depression-like behaviors in mice.
Although running on a wheel was able to improve the symptoms of depression, mice genetically engineered to lack adiponectin did not benefit as much from the exercise as mice capable of producing adiponectin. Adiponectin-lacking mice also showed a reduced activation of the protein kinase AMPK.
Using cell lines lacking the adiponectin receptors ADNR1 and ANDR2, the authors were able to show that the increase in cell proliferation required ADNR1 but not ADNR2. Taken together, the results suggest that exercise increases the production of adiponectin, which crosses the blood-brain barrier and is recognized by ADNR1 receptors on the brain. Activation of the ADNR1 receptors then induces downstream changes such as AMPK phosphorylation, which ultimately alleviate depression-like behaviors.
The researchers note that adiponectin can also be induced by treatment with peroxisome proliferation-activated receptor-γ (PPARγ) agonists and even herbs such as Radix Astragali, suggesting that these could potentially be used to treat depression.
The article can be found at: Yau et al. (2014) Physical Exercise-Induced Hippocampal Neurogenesis and Antidepressant Effects are Mediated by the Adipocyte Hormone Adiponectin.
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