Scientists identify gene that regulates body weight in humans and mice

November 21, 2013
Research has pointed to the importance of genetic factors in human obesity and has shown that heritability plays a role in 40 percent to 90 percent of cases. Now investigators reporting online November 21 in The American Journal of Human Genetics, published by Cell Press, have found that loss of a particular gene's function in humans and mice causes morbid obesity. The study of a morbidly obese family provides new insights into the pathways that control body weight and nutritional status, and the results could be useful for designing therapies for obesity and malnutrition. Credit: John Martignetti

Research has pointed to the importance of genetic factors in human obesity and has shown that heritability plays a role in 40% to 90% of cases. Now investigators reporting online November 21 in The American Journal of Human Genetics, published by Cell Press, have found that loss of a particular gene's function in humans and mice causes morbid obesity. The study of a morbidly obese family provides new insights into the pathways that control body weight and nutritional status, and the results could be useful for designing therapies for obesity and malnutrition.

"Starting with gene discovery in a single family with morbid obesity, these studies led to the identification a gene that seems to be fundamental to regulating nutritional status," says one of the senior authors, Dr. John Martignetti of the Icahn School of Medicine at Mount Sinai in New York City. "This gene is shown to be present not only in humans and mice but also in the simplest known single-cell animal. Nature considers this gene so important that it has preserved its structure for more than 700 million years."

Drs. Martignetti and Adel Shalata, of the Ziv Medical Center Safed, Israel, and their team analized a large Israeli Arab family affected by autosomal-recessive and identified a truncating mutation in the gene that recently was found to encode CEP19, a ciliary protein. When the investigators deleted the Cep19 gene in mice, the animals became obese and diabetic and had increased appetites, decreased energy expenditure, and impaired fat metabolism.

"The mouse models we have generated, which can be more than twice as heavy as other mice and are insulin resistant, represent important research tools for basic biology and clinical testing," says Dr. Martignetti.

The researchers note that the of this ciliary protein in maintaining a balance between leanness and obesity remains unknown. Additional studies are needed if researchers are to determine the mechanisms behind CEP19's effects on appetite control, energy expenditure, and insulin signaling and sensitivity.

Uncovering the details behind the pathways that control body weight will only become more pressing with time. "Obesity is a global epidemic, affecting almost all areas of human health, from heart disease to cancer, and impacting upon most of the major causes of preventable death," says Dr. Martignetti. "Moreover, obesity rates are rising dramatically worldwide. If we are going to combat this disease, we need to understand its medical basis."

Explore further: Researchers discover gene that causes obesity in mice

More information: AJHG, Shalata et al.: "Morbid obesity in humans and mice resulting from inactivation of the ciliary protein MO1/CEP19.." dx.doi.org/10.1016/j.ajhg.2013.10.025

Related Stories

Researchers discover gene that causes obesity in mice

March 5, 2013
Researchers have discovered that deleting a specific gene in mice prevents them from becoming obese even on a high fat diet, a finding they believe may be replicated in humans.

Novel genetic mutations cause low metabolic rate and obesity

October 24, 2013
Researchers from the University of Cambridge have discovered a novel genetic cause of severe obesity which, although relatively rare, demonstrates for the first time that genes can reduce basal metabolic rate – how the ...

Gene mutation linked to obesity

July 18, 2013
Researchers at Boston Children's Hospital have identified a genetic cause of severe obesity that, though rare, raises new questions about weight gain and energy use in the general obese population. The research, published ...

Obese mums may pass health risks on to grandchildren

June 5, 2013
Health problems linked to obesity—like heart disease and diabetes—could skip an entire generation, a new study suggests.

Morbid obesity in women on the rise, study finds

April 4, 2013
(Medical Xpress)—A Deakin University study has found that the rate of morbid obesity in women increased by almost 70 per cent over a 10 year period.

Obesity suppresses cellular process critical to kidney health

October 5, 2013
Obesity increases a chronic kidney disease patient's risk of developing kidney failure.

Recommended for you

Gene variant activity is surprisingly variable between tissues

August 21, 2017
Every gene in almost every cell of the body is present in two variants called alleles—one from the mother, the other one from the father. In most cases, both alleles are active and transcribed by the cells into RNA. However, ...

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Ratfish
not rated yet Nov 21, 2013
So...which is more plausible: 1) 2/3rds of Americans' genes rapidly mutated over the last several decades and caused them to become overweight/obese even though they eat exactly as their ancestors did or 2) that people nowadays eat tons of garbage while sitting around watching TV, thus making them ever-fatter year after year?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.