2 Mutations Linked to High Leptin Levels Found in Adolescent Bulimics, Study Reports

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by Steve Bryson PhD |

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Mrp4 gene and obesity

Adolescents with an eating disorder who carry two obesity-related genetic mutations have high levels of the hunger-reducing hormone leptin in their blood, a Mexican study has found. Higher levels of leptin were also found in participants who reported more binge-eating episodes.  

The findings point to a possible mechanism of leptin resistance making the hormone less effective in these patients. 

The study, “Interaction of FTO rs9939609 and the native American-origin ABCA1 p.Arg230Cys with circulating leptin levels in Mexican adolescents diagnosed with eating disorders: preliminary results,” was published in the journal Psychiatry Research.

Leptin is released from fat cells to send signals to the brain that suppress hunger and regulate energy balance. Levels of leptin in the blood have been found altered in people with eating disorders.

Recent genome-wide studies have identified genetic variants associated with eating behaviors and obesity. Examples are found in the FTO and ABCA1 genes. 

A mutation in ABCA1 — known as rs9282541-A — was found to regulate HDL cholesterol levels and obesity, while an FTO variant — rs9939609-A — was associated with obesity and an inability to control eating behaviors after meals. However, how these genes modulate leptin remain unexplored. 

In the study, researchers based at the National Institute of Genomic Medicine, in Mexico, and their collaborators recruited 99 adolescents with confirmed eating disorders (average age of nearly 14 years) to investigate the effect of the FTO and ABCA1 genetic variants and their association with blood leptin levels. 

Among the participants (all were of Mexican heritage), 21 had binge-eating disorders, 22 had anorexia nervosa — characterized by abnormally low body weight and an intense fear of gaining weight — and 56 had bulimia nervosa, in which individuals binge eat and then purposely purge their intake through vomiting. 

The study included 69 female and 30 male adolescents. According to their body mass index (BMI), 20 were considered obese, 13 were overweight, and two were underweight. 

Participants answered the Questionnaire on Eating and Weight Patterns-5, and other psychiatric complications were assessed using the MINI-kid questionnaire. Blood was collected to measure leptin levels and for genetic analysis. 

Other psychiatric disorders were identified in 82 individuals, 37 of whom reported a major depressive episode, 36 had attention-deficit/hyperactivity disorder, 22 were at risk for suicide, and 13 experienced generalized anxiety disorder

Overall, mean leptin levels were 2.01. Higher hormone levels were associated with greater BMI. No differences in leptin levels were found between males and females, and across age ranges.

Leptin levels differed based on the specific eating-disorder diagnosis. The highest levels were in adolescents with a binge-eating disorder (2.28) and the lowest levels were found in those with anorexia (1.65). 

Participants who had more than three episodes of binge eating in a week had the highest leptin levels (2.53). The group with at least one binge episode per week had more leptin (2.23) than patients without such episodes (1.68). 

The results “could be pointing to a deregulation in the brain of the signal emitted by leptin to reduce food intake, pointing to a possible leptin resistance mechanism in patients with [binge-eating disorder] or [bulimia],” the investigators wrote. 

An assessment of psychiatric conditions found that individuals with an anxiety disorder had a higher level of leptin than those without the diagnosis.

Six participants carried the FTO rs9939609-A variant, and two had the ABCA1 rs9282541-A mutation. These variants were not associated with BMI or psychiatric conditions. 

The team found an association between the rs9282541-A mutation in ABCA1 and the ratio of weight to leptin levels. Adolescents carrying this variant had a higher ratio compared to non-carriers.

Significant differences in leptin levels were found in participants in this group, unlike in carriers of the other variant.

Participants with bulimia who carried both variants had the highest leptin levels. Those with binge eating disorders and anorexia had a trend toward higher levels of leptin, but the difference did not reach statistical significance. 

“In conclusion, we found an interaction between ABCA1 [rs9282541-A] and FTO rs9939609 with circulating leptin levels, in patients diagnosed with eating disorders suggesting a potential role of specific genetic variation in the regulation of appetite,” the scientists wrote. 

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