A Brain Protein may Affect Fat Deposition

Obesity is characterized by the presence of excess fatty tissue, called adipose, which usually accumulates around the waist. People with a larger waist circumference are considered more obese and are often of a higher weight and higher cardiovascular risk; obesity is a major health concern associated with increased morbidity and mortality from cardiovascular complications, such as hypertension, diabetes, and heart disease. The condition is the product of both environment (diet and lifestyle) and genetics.

Despite popular clamor for discoveries of an “obesity gene”, the disorder is most likely a polygenic disorder, meaning that a number of genes contribute to its development and maintenance. The disorder is also estimated to be 30–70 percent heritable, meaning that it runs in families with a roughly 50/50 chance of a person having to struggle with it if his/her parents were obese. Research has identified a few genes with single nucleotide polymorphisms (SNPs) that are associated with increased waist circumference and increased body mass index (BMI), another measure of obesity; the genes include FTO, which is also associated with diabetes susceptibility and food selection, and MC4R, which is associated with fat and energy metabolism.

In 2009, an analysis of eight different research projects that investigated more than 31,000 obese individuals found an association between waist circumference and a variant of neurexin 3 (NRXN3), a protein found in the brain. Heard-Costa et al. published their findings in the Public Library of Science under the title “NRXN3 Is a Novel Locus for Waist Circumference” (PLoS Genet 5(6), June 2009). The research group demonstrated an association between an SNP in the NRXN3 gene (called a variant) and larger waist circumference, higher BMI, and obesity (not unexpectedly because a larger waist circumference would imply a higher BMI because it is based on the relativity of height to weight, and this would imply obesity because a higher BMI is the definition of obesity). The findings of the study indicated that the variant influences overall adiposity, that is the deposition of fatty tissue throughout the body, not just in the abdominal region. This indicates a more complex and generalized role of the protein in fat storage.

However, the role of SNPs in disease is tricky because their presence and effect differ among ethnic populations. A study of the Japanese population published in August 2010 (epub ahead of print, Hotta et al. Journal of Human Genetics) found no association of the NRXN3 variant and increased waist circumference.

Heard-Costa’s findings are interesting though because NRXN3 is known to be present in the central nervous system, and it is associated with alcohol dependence, cocaine addiction, and illegal drug abuse. The area of the brain in which the addiction pathway travels also takes part in the learning and reward responses. The addition of fat deposition to the roles of the protein raises the question of obesity as a byproduct of addiction. To what extent does food addiction or desire contribute to increased fat deposits and, consequently, weight gain and obesity? The study suggests that obesity is a centrally-mediated disorder with physiological components, which means it may be treatable by medical means, much like attempts are being made to overcome cocaine addiction with pharmaceuticals.