Gene produces hormones that lead to obesity

Jul 14, 2008

(PhysOrg.com) -- Obesity and common weight gain share a genetic basis. Professor Philippe Froguel, from Imperial College in Great Britain, and his team from the laboratoire Génomique et physiologie moléculaire des maladies métaboliques (CNRS/ Université Lille 2 / Institut Pasteur de Lille), in collaboration with teams from Inserm and Danish, Swiss and German partners, have discovered a new obesity gene that plays an essential role in the maturation of several key hormones that control food intake.

Mutations in this gene increase the risk of severe obesity and can lead to excessive weight. These results were published online in the journal Nature Genetics.

The gene PCSK1 produces an enzyme called proconvertase 1 which activates several hormones and circulating peptides that are essential to life and are involved in controlling appetite – examples include insulin, glucagon (and derivatives such as GLP1, a new treatment for type 2 diabetes) and proopiomelanocortin (which makes a person feel full).

This enzyme had been previously identified as being almost completely ineffective in three obese patients with abnormalities in intestinal functioning.

The French-British team became interested in the frequent mutations in the gene PCSK1 which modify the structure of proconvertase 1. They showed that the enzyme activity in the mutated gene is intermediate between what was seen in the three obese patients and that of a non-mutated gene. These mutations increase the risk of becoming severely obese and have contributed to weight gain in, among others, French, Swiss, and Danish populations. Carriers of mutations of the PCSK1 gene also have a tendency to be hypoglycemic after meals due to insulin abnormalities linked to this mutation.

This discovery shows that apparently minor abnormalities in a key enzyme for the maturation of several hormones involved in controlling appetite (insulin, GLP1, melanocortin) are enough to significantly increase the risk of severe obesity and to lead to excessive weight in the general population.

After the early 2008 discovery that frequent variants in the melanocortin 4 receptor play a role in obesity (also published in Nature Genetics), the French-British team demonstrated that severe obesity and common weight gain have a common genetic base principally linked to defects in the complex hormone system (including some hormones produced by the intestine) and in specific receptors in certain areas of the brain that regulate food intake and satiation. At a time when the prevalence of morbid obesity (body-mass index greater than 40 kg/m2) has doubled in the past decade, these results highlight the importance of early dietary control to prevent and reduce obesity.

This study was carried out thanks to volunteers from families with obese children.

Citation: Common nonsynonymous variants in PCSK1 confer risk of obesity, Michael Benzinou et al. Nature Genetics, July 6, 2008.

Provided by CNRS

Explore further: DNA signature found in ice storm babies

add to favorites email to friend print save as pdf

Related Stories

Cell biology: Flushing out fats

Dec 19, 2012

The Wip1 protein is important for survival, but mutations that inactivate it carry some surprising features. "A lack of Wip1 results in an excessive immune reaction to infectious organisms, in some cases ...

Oversized fat droplets: Too much of a good thing

Aug 29, 2012

As the national waistline expands, so do pools of intra-cellular fat known as lipid droplets. Although most of us wish our lipid droplets would vanish, they represent a cellular paradox: on the one hand droplets ...

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0