A leptin missense mutation associated with hypogonadism and morbid obesity

Strobel, Alexander; Issad, Tarik; Camoin, Luc; Özata, Metịn; Ad, Strosberg

doi:10.1038/ng0398-213

Cited by 1,077 publications

(586 citation statements)

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“…Acute dietary fasting also profoundly suppresses serum leptin levels and attenuates the leptin pulse area and incremental pulse amplitude (Bergendahl et al, 2000). In humans, as in mice, congenital absence of leptin or functional leptin receptor causes severe obesity accompanied by neuroendocrine abnormalities (Montague et al, 1997;Strobel et al, 1998;Ozata et al, 1999;Clement et al, 1998). Interestingly, the neuroendocrine defects that are present in leptin-deficient rodents and in leptin-resistant humans differ from each other, which indicates that the role of leptin in mediating the neuroendocrine response to starvation may be different in humans versus rodents (Montague et al, 1997;Strobel et al, 1998;Ozata et al, 1999;Clement et al, 1998).…”

Section: Leptinmentioning

confidence: 99%

“…In humans, as in mice, congenital absence of leptin or functional leptin receptor causes severe obesity accompanied by neuroendocrine abnormalities (Montague et al, 1997;Strobel et al, 1998;Ozata et al, 1999;Clement et al, 1998). Interestingly, the neuroendocrine defects that are present in leptin-deficient rodents and in leptin-resistant humans differ from each other, which indicates that the role of leptin in mediating the neuroendocrine response to starvation may be different in humans versus rodents (Montague et al, 1997;Strobel et al, 1998;Ozata et al, 1999;Clement et al, 1998). Data from Chan et al (2003) has suggested that a reduction of circulating leptin levels in lean men regulates the acute fasting-induced changes that occur in the HPG axis and, in part, the changes that occur in the hypothalamic-pituitarythyroid (HPT) axis and in IGF-1-binding capacity, but it is not responsible for changes in the HPA, rennin-aldosterone, and GH-IGF-1 axes associated with acute fasting (Chan et al, 2003).…”

Section: Leptinmentioning

confidence: 99%

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Caloric restriction: Impact upon pituitary function and reproduction

Martin

Golden

Carlson

et al. 2008

Ageing Research Reviews

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Reduced energy intake, or caloric restriction (CR), is known to extend life span and to retard agerelated health decline in a number of different species, including worms, flies, fish, mice and rats. CR has been shown to reduce oxidative stress, improve insulin sensitivity, and alter neuroendocrine responses and central nervous system (CNS) function in animals. CR has particularly profound and complex actions upon reproductive health. At the reductionist level the most crucial physiological function of any organism is its capacity to reproduce. For a successful species to thrive, the balance between available energy (food) and the energy expenditure required for reproduction must be tightly linked. An ability to coordinate energy balance and fecundity involves complex interactions of hormones from both the periphery and the CNS and primarily centers upon the master endocrine gland, the anterior pituitary. In this review article we review the effects of CR on pituitary gonadotrope function and on the male and female reproductive axes. A better understanding of how dietary energy intake affects reproductive axis function and endocrine pulsatility could provide novel strategies for the prevention and management of reproductive dysfunction and its associated comorbidities.

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Section: Leptinmentioning

confidence: 99%

Section: Leptinmentioning

confidence: 99%

Caloric restriction: Impact upon pituitary function and reproduction

Martin

Golden

Carlson

et al. 2008

Ageing Research Reviews

View full text Add to dashboard Cite

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“…3, OMIM #164160) has been found mutated in very rare forms of human obesity. 2,3 The identification of a polymorphic tetranucleotide repeat in the 3 0 flanking region of the LEP gene (LEP-tet) provided an useful marker for linkage and association studies between this gene and a number of phenotypes other that obesity, such as noninsulin-dependent diabetes mellitus, hypertension and insulin resistance syndrome. 4,5 LEP-tet is composed by 15 alleles, which can be divided into two groups with different size distribution: a shorter one (class I) and a longer one (class II).…”

Section: Introductionmentioning

confidence: 99%

Microsatellite polymorphism of the human leptin gene (LEP) and risk of cardiovascular disease

et al. 2005

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Background: No data have been so far reported on the relationship between polymorphisms of LEP gene and cardiovascular disease. Patients and methods: We genotyped a tetranucleotide repeat mapped in the 3 0 UTR of the LEP gene (LEP-tet) in 109 subjects with cardiovascular events and in 109 control subjects. Results: Univariate analysis and multivariate logistic regression analysis adjusted for age, gender, smoking status, history of hyperlipidemia, hypertension or diabetes showed not significant association between the genotype of the LEP-tet and cardiovascular diseases. Moreover, no differences were observed in the plasma leptin concentrations between cases and control subjects (22719 vs 22714 ng/ml, P ¼ 0.52) and in relation to the LEP-tet classes or carriage of specific allelels (P ¼ 0.76 for the association between LEP-tet classes and leptin levels in overall analysis). Conclusions: In conclusion, our data do not support an association between the LEP-tet microsatellite polymorphism of the human LEP gene and cardiovascular diseases.

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“…Accordingly, mutations in the ob gene encoding leptin produce hyperphagia and morbid obesity in mice (ob/ob mice) 5,17 and humans. [36][37][38][39][40] Similar to states of starvation, leptin deficiency also leads to deficits in the reproductive, thyroid, and adrenal axes. [41][42][43][44] Moreover, exogenous leptin corrects these manifestations in leptin-deficient mice [45][46][47][48] and humans.…”

mentioning

confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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A leptin missense mutation associated with hypogonadism and morbid obesity

Cited by 1,077 publications

References 13 publications

Caloric restriction: Impact upon pituitary function and reproduction

Caloric restriction: Impact upon pituitary function and reproduction

Microsatellite polymorphism of the human leptin gene (LEP) and risk of cardiovascular disease

Body weight is regulated by the brain: a link between feeding and emotion

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