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Adipose tissue plays a dynamic role in whole-body energy homeostasis by acting as an endocrine organ. Collective evidence indicates a strong link between neural influences and adipocyte expression and secretion of leptin. Developmental changes in these relationships are considered important for pubertal transition in reproductive function. Leptin augments secretion of gonadotropin hormones, which...
There is an intimate interplay between systemic insulin action and the actions of the adipocyte-derived proteins leptin and adiponectin. Concordant findings in humans and rodents demonstrate that leptin gates critical physiological functions to the prevailing nutritional state, however the physiological functions of adiponectin are less convincingly established. Murine evidence suggests that adiponectin...
It is well established that individuals with the metabolic syndrome have a significantly increased risk of cardiovascular disease and much effort has been expended to elicit the underlying mechanisms. Various studies have proposed that excessive or deficient physiological effects mediated by leptin make an important contribution, yet many paradoxical observations often preclude a clear definition...
A number of studies indicate that a growing list of cancers may be influenced by obesity. In obese individuals these cancers can be more frequent and more aggressive resulting in reduced survival. One of the most prominent and well characterized cancers in this regard is breast cancer. Obesity plays a complex role in breast cancer and is associated with increased inflammation, angiogenesis and alterations...
Since the initial identification of leptin as the product of the ob gene in 1994, the signaling pathways by which this hormone alters cell physiology have been the subject of extensive investigations. The fact that leptin can induce nitric oxide (NO) production was first demonstrated in studies of the pituitary gland and pancreatic islets. A large number of additional studies further showed that this...
The studies based on candidate genes and encoded proteins known to cause severe obesity in rodents, have shown that these genes also contribute to human early-onset obesity especially for those involved in the leptin pathway: the leptin (LEP) and leptin receptor (LEPR) genes. Since 1997, less than 20 individuals carrying a LEP gene mutation have been identified. Patients are mostly characterized by...
Recombinant methionyl human leptin (r-metHuLeptin) was first used as a replacement therapy in patients bearing inactivating mutations in the leptin gene. In this indication, it was shown since 1999 to be very efficient in inducing a dramatic weight loss in rare children and adults with severe obesity due to the lack of leptin. These first clinical trials clearly showed that r-metHuLeptin acted centrally...
Despite growing evidence for adipose tissue regulation of bone mass, the role of the adipokine leptin in bone remodeling remains controversial. The majority of in vitro studies suggest leptin enhances osteoblastic proliferation and differentiation while inhibiting adipogenic differentiation from marrow stromal cells. Alternatively, some evidence demonstrates either no effect or a pro-apoptotic action...
Two years ago, the Lasker Award was shared by Douglas Coleman and Jeffrey Friedman for their discovery of leptin, a hormone that exerts a key role in the central regulation of appetite and body weight. Douglas Coleman is recognized as the researcher who raised the hypothesis and predicted that a circulating satiety factor was lacking in the ob/ob mouse, and predicted that this factor acted at the...
Adipose tissue produces leptin and adiponectin – energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine studies. Leptin and adiponectin and their respective receptors are expressed in the human lung. The association between systemic or airway leptin and asthma in humans is currently controversial, particularly among adults. The majority...
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