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Scientists in Iceland and at Oxford University and King's College in London announce that they have discovered a single, master gene that controls the amount of fat that accumulates in the human body.

May Be Responsible for High Cholesterol and Diabetes, British Researchers Say

This gene also regulates the effects of jiggly subcutaneous fat on the muscles and the liver that may cause high cholesterol, diabetes, and a form of skin cancer known as basal cell carcinoma.

Researchers study fat samples taken in biopsies from 800 sets of female twins in the United Kingdom and 600 other people in Iceland. They found that a gene called basic transcription element-binding protein 5, now renamed Krüppel-like factor 14 or KLF14, sends signals that control the growth of fat cells, and that the growth of fat cells in turn changes how the liver and the muscles respond to insulin and absorb sugar. Excess sugar, in turn, becomes triglycerides that may be converted into cholesterol.

Like many other human genes, this gene is a member of a family of genes that scientists originally observed in fruit flies. In both fruit flies and humans, the Krüppel genes regulate cell growth signals. Some genes in this group code proteins that override genetic protection against cancer. Other genes in this family cause smooth cells in the lining of arteries to proliferate and toughen the artery around cholesterol plaques and are involved in increasing the rate at which blood clots form.

The KLF14 gene and other genes in this family can interfere with "good" genes that stop the growth of cancer cells in the S phase, right after all the genetic material has been copied into a new cancer cell. This is the time at which the newly formed cancer cell is least active and most susceptible to elimination by the immune system. This effect is most noticeable in "slow-growing" cancers such as basal cell carcinoma, the most common cancer of the skin.

An oddity of the KLF14 gene is that, while people inherit one copy of the gene from their fathers and one copy of the gene from their mothers, only the gene inherited from the mother is active.

Will scientists someday be able to switch off the KLF14 gene to cure obesity, diabetes, high cholesterol, and cancer? It is unlikely that this one discovery will lead to magic bullets for any of these diseases. Genetics is just one factor in the development of these diseases, and there may be a protective role for KLF14 that has not yet been discovered. This exciting genetic discovery, however, may lead to the creation of treatments for a wide range of disease that are very helpful for certain individuals in the context of healthy lifestyles and good medical care.

  • the MuTHER Consortium, Small KS, Hedman AK, Grundberg E, Nica AC, Thorleifsson G, Kong A, Thorsteindottir U, Shin SY, Richards HB
  • the GIANT Consortium
  • the MAGIC Investigators
  • the DIAGRAM Consortium, Soranzo N, Ahmadi KR, Lindgren CM, Stefansson K, Dermitzakis ET, Deloukas P, Spector TD, McCarthy MI. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nat Genet. 2011 May 15. [Epub ahead of print]
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