Salle 5, Site Marcelin Berthelot
Open to all
-

Starvation is a major cause of death in the world, killing more than 6 million children each year. Throughout evolution famine has been a constant threat to all animal species. As a result, evolution has selected for powerful mechanisms to maintain life even under conditions in which nutrients are severely limited. When body fat disappears, it is essential that the body maintain levels of plasma glucose that are sufficient to nourish the brain. The famous French scientist Claude Bernard was the first to call attention to this compensation with his famous quotation: "La fixité du milieu intérieur est la condition d'une vie libre et indépendante"

Recently, our laboratory found that a peptide hormone, ghrelin, is essential to the survival of chronically starved mice. Ghrelin was discovered in 1999 by Kojima and Kangawa in Japan. It is a peptide of 28 amino acids that has a unique modification, namely, an 8 carbon fatty acid, octanoate, attached in thioester linkage to a serine at position three. The octanoate modification is essential for ghrelin activity, and it is conserved in all vertebrate species.

Most ghrelin is produced primarily in the stomach. Its concentration in plasma rises steeply before meals, and it declines dramatically following eating. Administration of excess ghrelin to rodents and humans increases food intake. Itwas therefore postulated that ghrelin provides the signal that makes animals hungry prior to meals. This hypothesis was disproven when the gene for ghrelin and its receptor were eliminated in mice through homologous recombination. When deprived of food, the ghrelin-deficient mice became just as hungry as wild-type mice. Moreover, when fed a high-calorie diet the ghrelin-deficient mice became just as obese as wild-type mice.

Ghrelin was discovered because of its ability to release growth hormone from pituitary cells. Nevertheless, ghrelin-deficient mice grew normally and had no signs of growth hormone deficiency. Therefore, the true function of ghrelin was an enigma.