The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review
Summary
Leptin and ghrelin are two hormones that have been recognized to have a major influence on energy balance.
Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. As a growing number of people suffer from obesity, understanding the mechanisms by which various hormones and neurotransmitters have influence on energy balance has been a subject of intensive research. In obese subjects the circulating level of the anorexigenic hormone leptin is increased, whereas surprisingly, the level of the orexigenic hormone ghrelin is decreased. It is now established that obese patients are leptin-resistant. However, the manner in which both the leptin and ghrelin systems contribute to the development or maintenance of obesity is as yet not clear. The purpose of this review is to provide background information on the leptin and ghrelin hormones, their role in food intake and body weight in humans, and their mechanism of action. Possible abnormalities in the leptin and ghrelin systems that may contribute to the development of obesity will be mentioned. In addition, the potentials of leptin and ghrelin as drug targets will be discussed. Finally, the influence of the diet on leptin and ghrelin secretion and functioning will be described.
Introduction
In most humans, body weight is maintained in a stable condition. Humans can have the same body weight for many years. To have a constant weight, there must be an energy balance; energy intake has to be equal to energy expenditure. However, when the energy balance gets disturbed, this may eventually lead to sustained weight problems like, for example, in obese subjects. A growing number of people, including children, suffer from obesity, particularly in the Western society. In the United States, the prevalence of obesity is very high. In 1999–2002, 65.1% of the adults were overweight, of whom 30.4% were obese. In 2002, the prevalence of obesity in Europe ranged from 9% in Italy to 30% in Greece (2). Morbidity and mortality increase gradually with excess of body mass index (BMI). Therefore, many investigators try to identify the mechanisms behind the imbalance between energy intake and energy expenditure.
Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake and body weight are leptin and ghrelin. Both originate in the periphery and signal through different pathways to the brain, particularly to the hypothalamus. In the hypothalamus, activation of the leptin or ghrelin receptor initiates different signalling cascades leading to changes in food intake. As both the leptin and ghrelin systems are disturbed in obesity, it is important to reveal their mechanism of action for the purpose of developing novel therapeutic interventions.
Authors: M. D. Klok, S. Jakobsdottir, M. L. Drent
Department of Endocrinology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Date: 24 August 2006
Link: https://onlinelibrary.wiley.com/doi/10.1111/j.1467-789X.2006.00270.x
Nutrigenomics Institute is not responsible for the comments and opinions included in this article
