The team has discovered a new function of the gene H19. This gene proves to have a unique protective effect against the development of overweight and consequently could affect the onset of overweight-associated disease such as diabetes, overweight and cardiovascular diseases.

H19 belongs to the app. one percent of our genes, which we - as opposed to the remaining 99 percent - inherit exclusively from either our mother or father, the so-called monoallelic genes.

As a result of extensive studies, the researchers have also discovered how genes derived from our father primarily lead to the development of white fat tissue, which most often are found on the stomach, thighs and backside, and which can lead to metabolic diseases.

Likewise, it appears that genes from our mother primarily lead to the development of brown fat tissue, which is characterized by having a protective effect against obesity.

In their view the results could constitute a first step towards the development of better treatments of obesity.

- By using mouse models, we have identified that the gene H19 performs a form of gene control in brown fat cells. We have been able to demonstrate that an overexpression of the H19 gene in mice protects against obesity and insulin resistance. In addition, we have been able to detect similar patterns of gene control in obese people. We therefore believe that our results can be the first step towards developing groundbreaking new and improved treatments for obesity-related diseases, says the senior author.

Authors observed maternally expressed, imprinted lncRNA H19 increased upon cold-activation and decreased in obesity in BAT (brown adipose tissue). Inverse correlations of H19 with BMI were also observed in humans. H19 overexpression promoted, while silencing of H19 impaired adipogenesis, oxidative metabolism and mitochondrial respiration in brown but not white adipocytes.

In vivo, H19 overexpression protected against DIO, improved insulin sensitivity and mitochondrial biogenesis, whereas fat H19 loss sensitized towards HFD weight gains.

Strikingly, paternally expressed genes (PEG) were largely absent from BAT and authors demonstrated that H19 recruits PEG-inactivating H19-MBD1 complexes and acts as BAT-selective PEG gatekeeper. 

https://www.sdu.dk/en/om_sdu/fakulteterne/naturvidenskab/nyheder2018/2018_09_05_bruntfedt

https://www.nature.com/articles/s41467-018-05933-8