Do Nerve Genes Determine Excess Skin Fat?

As any clinician knows, patterns of fat deposition tend to vary greatly even in people with similar amounts of total body fat.

Not only are there the typical “male” and “female” patterns (commonly referred to as “apple” and “pear” shape) but there are also important differences in how much of excess fat is stored underneath the skin versus inside the abdomen or in other organs.

These patterns of fat distribution have important consequences for the health risks associated with excess fat – excess skin or subcutaneous fat tends to have little impact on cardiometabolic risk (some even claim it may be protective) whereas excess fat stored in muscle or internal organs are linked to a wide range of health problems like diabetes, fatty liver disease, or sleep apnea.

Why people differ in their propensity to deposit fat in these different locations is not entirely clear. Some of this is certainly regulated by sex hormones and cortisol but it has long been suspected that there may also be genetic factors at play.

In a rather surprising twist, this notion is now supported by a paper just published in PLoS one by Kyung-Tai Lee and colleagues from the National Institute of Animal Science in Suwon, North Korea.

Based on previous studies that showed a high heritability for backfat thickness (between 50% and 70%) and intramuscular fat (38% and 67%) content in pigs, Lee and colleagues first sequenced a region of pig chromosome 6 that had been shown to affect fatness traits in these animals.

This led to the identification of 13 genes, 8 of which are interestingly also involved in psychiatric disorders and can affect nerve growth and function. All of these genes appeared to be related to back fat thickness (i.e. excess skin fat) rather than to muscle fat.

The researchers next examined the relationship between markers of these genes and skin fat thickness in a cohort of 8,842 Korean individuals. Surprisingly 8 of the same genes that were associated with back fat in pigs were also associated with skin fat thickness in this population. (For expert readers, the 8 neuronal genes responsible for subcutaneous fat thickness were: NEGR1, SLC44A5, PDE4B, LPHN2, ELTD1, ST6GALNAC3, ST6GALNAC5, and TTLL7).

From these studies the researchers conclude that common variations in these neuronal genes may surprisingly determine not only the genetic risk for obesity but also play an important role in the development of excess skin fat.

How exactly these genes regulate skin fat will certainly now be the focus of intense research.

To clinicians, these studies should serve as a reminder that the regulation and function of fat tissue is staggeringly complicated and fascinating.

Clearly fat distribution is not just a function of calories in and calories out.

Edmonton, Alberta

Lee KT, Byun MJ, Kang KS, Park EW, Lee SH, Cho S, Kim H, Kim KW, Lee T, Park JE, Park W, Shin D, Park HS, Jeon JT, Choi BH, Jang GW, Choi SH, Kim DW, Lim D, Park HS, Park MR, Ott J, Schook LB, Kim TH, & Kim H (2011). Neuronal genes for subcutaneous fat thickness in human and pig are identified by local genomic sequencing and combined SNP association study. PloS one, 6 (2) PMID: 21311593