Three Genes Link Obesity and Mood Disorders, Study Suggests

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by Steve Bryson PhD |

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Three genes with epigenetic changes — those related to gene activity — are associated with both obesity and mood disorders, such as depression, a review study reported.

Findings showed that these genes are linked to inflammatory processes. 

The study, “The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review,” was published in the International Journal of Molecular Sciences and conducted by a team from Iran.

Mood disorders are common to people with obesity. Studies suggest that both genetics and environment play a role in the development of both conditions. It is also “well-established that 12% of the responsible genes for obesity are shared with depression,” the researchers wrote.

Beyond mutations in specific genes, changes in epigenetic mechanisms — that control whether a gene is active or silent — may be responsible for the co-development of these disorders. 

In particular, DNA methylation is an epigenetic mechanism whereby small molecules called methyl groups are added to a particular gene, turning it off so that no protein is produced. 

However, whether changes in DNA methylation occur in genes associated with both obesity and mood disorders remains unclear.

“The critical question is whether epigenetic changes in overlapped genes could cause obesity and mood disorders,” the researchers wrote. “In other words, mood disorders, especially depression, may result in obesity through DNA methylation of the shared genes, which could affect the body composition.”

To find out, they looked for studies with a focus on alterations in genes that overlap in people with obesity or mood disorders.

Their search covered several medical databases to identify studies with no restrictions on language, publication period, patients’ age, or study design.

A search to find genes linked to obesity looked at studies that are part of the epigenome-wide association study (EWAS) — an examination of genome-wide markers, such as DNA methylation, to find associations between epigenetic variation and particular characteristics, including diseases. 

A second search was conducted to find associations between the epigenome and mood disorders, including depression, bipolar disorder, or suicide. 

After excluding studies that investigated gene mutations or other diseases such as autoimmune disorders, cancer, and inflammation-related conditions, a total of 10 studies were identified for this analysis. 

From these, three genes — TAPBP, SORBS2, and BDNF — had changes in DNA methylation associated with obesity and mood disorders. 

The TAPBP gene carries instructions to make a protein called tapsin, vital for proper immune responses. Mice with mutations in TAPBP show defects in immune defense. 

TAPBP is linked to both obesity and mood disorders through a pathway known as JNK, which plays a key role in the inflammatory response. As seen in tissues isolated from people with obesity, inflammatory factors can cause continuous activation of JNK.

In turn, the SORBS2 gene, which codes for a protein called sorbin, is involved in several biological pathways. Lower activity of this gene has been reported in people with mood disorders. SORBS2 methylation has also been associated with body mass index, a measure of body fat based on weight and height.

SORBS2 is related to mood disorders through a pathway called Notch, which is important in regulating nerve cell growth and immune responses. Proinflammatory proteins activate Notch signaling, as observed in a variety of inflammatory disorders. 

The BDNF gene codes for a member of nerve cells growth proteins, important in the maintenance and survival of nerve cells. As with the SORBS2 gene, the activity of BDNF is reduced in people with depression, and methylation changes have been related to obesity and obesity. 

BDNF is considered a potential mediator of anti-inflammatory effects. Its neuroprotective potential is supported by pathways regulated by the production of inflammatory signaling proteins. 

“As the results … exhibited that TAPBP, BDNF, and SRBP2 are related together by inflammatory pathways, we hypothesis that hypermethylation in these genes might play a crucial role in the co-occurrence of obesity and mood disorders due to the inflammation process,” the investigators wrote. 

“Future studies should focus on the molecular pathophysiology of these disorders in the hope of opening new approaches for target treatment,” they added.

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