leptin and pyroglutamyl-histidyl-glycine

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.

Topics: Alzheimer Disease; Animals; Appetite Depressants; Disease Models, Animal; Energy Metabolism; Homeostasis; Humans; Leptin; Neuroprotective Agents; Oligopeptides; Pyrrolidonecarboxylic Acid

It is suggested that the symptoms of anorexia nervosa are physiological responses to starvation. There is no evidence of a neural or non-neural dysfunction that predisposes women for anorexia nervosa and the endocrine and psychological consequences of starvation are reversed once patients have re-learnt how to eat and regained a normal body weight. Because variability in the supply of food may be a common evolutionary condition, it is more likely that body weight is variable than constant in normal circumstances. The role of the neuroendocrine system in times of feast and famine is to allow the individual to adopt behavioral strategies as needed rather than maintaining body weight homeostasis. Treatment of anorexic patients should aim at reducing their high level of physical activity in order to facilitate eating.

Topics: Anorexia Nervosa; Feeding and Eating Disorders; Female; Humans; Leptin; Mental Disorders; Neurosecretory Systems; Oligopeptides; Pyrrolidonecarboxylic Acid; Starvation

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

Topics: Adrenergic beta-Antagonists; Animals; Cells, Cultured; Hypothalamus; Leptin; Mice; Mice, Inbred C57BL; Neuropeptides; Obesity; Oligopeptides; Osteoblasts; Osteogenesis; Pyrrolidonecarboxylic Acid; Receptor, Melanocortin, Type 4; Receptors, Adrenergic, beta; Receptors, Corticotropin; Receptors, Leptin; Sympathetic Nervous System