Mental Health

Uncovering the Relationship Between Obesity and Depression

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Obesity is a risk factor for several health conditions including diabetes, heart problems, liver disease and stroke. However, recent research has highlighted that obesity can also result in mental health disorders such as anxiety and depression. Studies conducted in the past have also established that obese and overweight people are more likely to suffer from mental health issues.

The role of the brain in controlling hunger

The human brain has different types of nerve cells that help in maintaining the energy balance in the body.

  • Agouti-related protein (AgRP): AgRP is one such nerve cell (also called a neuron) present in the hypothalamus (a part of the forebrain), that induces appetite and increases hunger. AgRP neurons also help in maintaining the circadian rhythm (sleep-wake cycle), fertility, and pain sensation of the body. AgRP neurons also act as an anxiolytic (anti-anxiety) agent, preventing anxiety during the state of fasting (low energy). AgRP neurons also release neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA), which are chemical agents (neurotransmitters) used by the nerve cells to communicate with each other. While NPY increases the impulse to eat more and promotes weight gain, GABA helps in maintaining a normal appetite.
  • Bed Nucleus of the Stria Terminus (BNST): BNST is a structure present in the base of the amygdala (a part of the forebrain) that acts along with the hypothalamus (present in the base of the brain) to control appetite. BNST also contains melanocortin 4 receptor (MC4R) neurons which help in preventing obesity by targeting the hunger hormone.

New study on the relationship between obesity and mental health

In a study published in the journal Molecular Psychiatry-Nature on 26th March 2021, scientists used a group of mice that were eight weeks old and divided them into two groups - the experiment group and the control group. The experiment group was fed with a high-fat diet, while the control group was given a standard or low-fat diet for 6 weeks.

The experiment aimed to determine the negative effects of obesity and the behavioural changes in the mice after getting the high-fat diet. To evaluate the behavioural changes, scientists included several tests such as open-field test, elevated-plus-maze test, tail suspension test, forced swim test, and marble-burying test in the study.

Results of the study

The study was carried out for 6 weeks, after which it was found that:

  • Mice fed with a high-fat diet showed a significant increase in body weight as compared to the control group which was given a low-fat diet.
  • Mice that were given the high-fat diet showed signs of depression and anxiety.
  • The mice in the experiment group showed no response of AgRP neurons to hunger. Therefore, there was an increased impulse to eat food and increased anxiety during fasting.
  • There was a decreased activity of GABAAR-α5 (a kind of neurotransmitter) in the experiment group, which led to the occurrence of anxiety and depression-like symptoms. Reduced activity of GABAAR-α5 has been associated with the development of various mental disorders such as anxiety, depression, autism spectrum disorder and Alzheimer’s disease.
  • The mice fed with high-fat food also showed increased activity of a receptor (5-HT3R) in melanocortin 4 receptor (MC4R) neurons. This resulted in abnormal hyperactivity of MC4R neurons, which promoted weight gain, anxiety and depression in the mice.

Scientists concluded that a high-fat diet can not only result in weight gain but can also lead to anxiety and depression. However, scientists tried to restore the normal functioning of the nerve cells to determine if it was possible to induce weight loss and eliminate the signs of mental dysfunction.

Reciprocating the action of the high-fat diet

Scientists used two different measures to reverse the action of the high-fat diet on brain cells.

  • The genetic changes: Researchers genetically enhanced the activity of GABAAR-α5 and disrupted the 5HT3R, which not only helped in reducing signs of mental dysfunctions but also reduced high-fat diet-associated obesity.
  • The drug cocktail: Scientists administered the combination of two anti-convulsant drugs, zonisamide and granisetron, in the mice which were fed with the high-fat diet. The results showed that the drugs acted on GABAAR-α5 and 5HT3R and reversed the mental dysfunction induced by the high-fat diet. The drug combination also promoted weight loss in obese mice.

What should be done to maintain a healthy weight?

Maintaining a healthy weight is essential for both physical and mental wellness. Working with a registered nutritionist to identify requisite calories and formulate a wholesome and nutritious meal plan is essential for a healthy mind and body. A few tips are listed below:

  • Consume a diet that has whole grains, healthy fats and protein-rich foods such as nuts (almonds, walnuts) and seeds (chia seeds, sunflower seeds), fatty fishes, eggs, soy and whole grains. Eat small portions during each meal.
  • Practise moderate-intensity exercise such as swimming, brisk walking and cycling for at least half an hour every day.
  • Reduce stress by practising meditation, yoga, tai chi and breathing or relaxation exercises.
  • Sleep for at least 7 to 8 hours a day.


This study helped scientists conclude that obesity and mental health conditions, especially anxiety and depression, have a two-way relationship with each other. The brain cells of two different parts of the brain, the hypothalamus and BNST work together to regulate the appetite as well as the stress response of the body. However, more research is needed to be done to firmly establish these links.

It is important to adopt healthy eating habits and live a physically active lifestyle to prevent obesity. At the same time, practising meditation, yoga and relaxation exercises are key to good mental health. One should consult a mental health expert if they experience signs of anxiety or depression.


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