Depressed and Fat?? Your Fat Tissue is Making it Worse
There has been a long and strong correlation between depression and obesity. Depression very often leads to overeating which in turn results in obesity. Then one becomes more depressed because of their physical appearance, eating to sooth the emotional pain resulting in a vicious cycle. Adding to this mix is the close association between obesity and type 2 diabetes. Of note is the fact that the prevalence of depression is twice as high in type 2 diabetics compared to the general population. As I said, a vicious cycle. The problem with some antidepressant medications is that they increase the risk of developing type 2 diabetes in high risk populations.
Now some very surprising results have emerged from studies in mice that demonstrate a strong correlation between a hormone secreted exclusively from fat tissue (adipose tissue) and depressive behaviors. This hormone is known as adiponectin. Visit the Adipose Tissue: Not Just Fat page for more information on this hormone. Adiponectin is exclusively secreted from adipose tissue and possesses strong anti-diabetic properties primarily due to the fact that its actions in the liver and skeletal muscle leads to increased insulin sensitivity. There is emerging clinical evidence pointing to a correlation between the levels of adiponectin in the blood and depression. What is not completely known is whether adiponectin plays a role in the pathophysiology of depression or whether the hormone is modulating depressive behaviors.
Results from a study published online July 9, 2012 in the Proceedings of the National Academy of Sciences (www.pnas.org/lookup/suppl/doi:10.1073/pnas.1202835109) demonstrate that adiponectin levels are a critical determinant of susceptibility to depression and most surprisingly that the hormone itself exhibits antidepressant-like activity.
The study was performed in mice and involved what is called a chronic social defeat stress model. Basically, weaker male mice are placed in a cage with a dominant male who proceeds to challenge and antagonize the weaker male. The outcomes of this type of model are highly similar to symptoms of depression in humans including social withdrawal and anhedonia (defined as the inability to experience pleasure from activities usually found enjoyable). When the plasma levels of adiponectin were analyzed in these mice they were found to be reduced. Of note is that the reduced levels of circulating adiponectin in the defeated mice were not correlated to reduced fat mass. In addition, there were no significant changes in adiponectin mRNA levels in adipose tissue of defeated mice compared to non-defeated control mice. In mice that have one adiponectin gene knocked out (referred to as haploinsufficiency), there was found to be a correlation to depressive behavior susceptibility similar to that seen in the defeated mice with who carry both wild-type copies of the adiponectin gene. In addition, if neutralizing antibodies to adiponectin are injected into the brains of mice they exhibit increased susceptibility to depressive-like behaviors. Conversely, if adiponectin is injected into the brains of mice the result is anti-depressive as measured by by the forced swim test and tail suspension tests that are widely used in the screening of antidepressant medications.
So here's the take home from this study. In humans with depression there is an increased tendency toward obesity which results in further depressive-like behaviors. As the level of fat tissue increases there is a concomitant drop in the level of circulating adiponectin. Thus, as one gets fatter the corresponding drop in the levels of the fat tissue hormone adiponectin result in increased depressive tendencies and also to increased likelihoods of developing type 2 diabetes.
Now some very surprising results have emerged from studies in mice that demonstrate a strong correlation between a hormone secreted exclusively from fat tissue (adipose tissue) and depressive behaviors. This hormone is known as adiponectin. Visit the Adipose Tissue: Not Just Fat page for more information on this hormone. Adiponectin is exclusively secreted from adipose tissue and possesses strong anti-diabetic properties primarily due to the fact that its actions in the liver and skeletal muscle leads to increased insulin sensitivity. There is emerging clinical evidence pointing to a correlation between the levels of adiponectin in the blood and depression. What is not completely known is whether adiponectin plays a role in the pathophysiology of depression or whether the hormone is modulating depressive behaviors.
Results from a study published online July 9, 2012 in the Proceedings of the National Academy of Sciences (www.pnas.org/lookup/suppl/doi:10.1073/pnas.1202835109) demonstrate that adiponectin levels are a critical determinant of susceptibility to depression and most surprisingly that the hormone itself exhibits antidepressant-like activity.
The study was performed in mice and involved what is called a chronic social defeat stress model. Basically, weaker male mice are placed in a cage with a dominant male who proceeds to challenge and antagonize the weaker male. The outcomes of this type of model are highly similar to symptoms of depression in humans including social withdrawal and anhedonia (defined as the inability to experience pleasure from activities usually found enjoyable). When the plasma levels of adiponectin were analyzed in these mice they were found to be reduced. Of note is that the reduced levels of circulating adiponectin in the defeated mice were not correlated to reduced fat mass. In addition, there were no significant changes in adiponectin mRNA levels in adipose tissue of defeated mice compared to non-defeated control mice. In mice that have one adiponectin gene knocked out (referred to as haploinsufficiency), there was found to be a correlation to depressive behavior susceptibility similar to that seen in the defeated mice with who carry both wild-type copies of the adiponectin gene. In addition, if neutralizing antibodies to adiponectin are injected into the brains of mice they exhibit increased susceptibility to depressive-like behaviors. Conversely, if adiponectin is injected into the brains of mice the result is anti-depressive as measured by by the forced swim test and tail suspension tests that are widely used in the screening of antidepressant medications.
So here's the take home from this study. In humans with depression there is an increased tendency toward obesity which results in further depressive-like behaviors. As the level of fat tissue increases there is a concomitant drop in the level of circulating adiponectin. Thus, as one gets fatter the corresponding drop in the levels of the fat tissue hormone adiponectin result in increased depressive tendencies and also to increased likelihoods of developing type 2 diabetes.
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