KLF14 and the genetic basis of obesity

Heart disease and obesity are inter-related, as well as being related to cholesterol and fat deposition in the body. On May 15, 2011, the journal Nature Genetics published work by a British research group that indicates a potential “master switch” for keeping all of these negative factors at bay.

The gene identified by the notation KLF14 was previously associated with type 2 diabetes and higher cholesterol levels – the new research identified how. The research team found that KLF14 acts as a trans regulator of gene expression in adipocytes – put simply, the gene appears to be a master regulator of protein production in fat cells. Fat cells and their distribution in the body are associated, most notably, with obesity, as well as diabetes and high cholesterol, which can lead to coronary artery disease and other cardiovascular complications. Knowing which switch initiates the signals that can lead to the development of these conditions may lead to a way to simply prevent them all at once.

Reuters quoted one of the research team members as saying, “KLF14 seems to act as a master switch controlling processes that connect changes in the behavior of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions”.

The researchers evaluated more than 20,000 genes in fat samples from 800 female twins to come across KLF14, which may be the key to treating, and preventing, metabolic disease. The results were confirmed in 600 subcutaneous fat samples from Iceland. This is the first study to show that small changes in a single regulatory gene can have a cascade of dramatic metabolic effects.

As explained by ScienceDaily, the activity of the KLF14 gene is inherited from one’s mother. The copy of the gene received from the father at conception is switched off, a common genetic process called imprinting. Only the maternal copy of the gene had effects on gene regulation. Also, mutations in the gene were associated with alterations in the control of gene expression, directly correlating the genotype with metabolic phenotype – processes that control metabolism and, potentially, disease.

Though not a master switch gene for obesity per se, KLF14 may be a master switch for metabolic phenotypes that can lead to obesity or cause complications in the presence of obesity. The findings shed light on the genetics underlying an uncomfortable condition many fight their entire lives and give some control over a previously uncontrollable force behind weight gain and obesity-related disease. In addition, the findings for KLF14 may create a roadmap for discovering the basis for other complex disease traits.