Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications

@article{Brennan2006DrugIT,
  title={Drug Insight: the role of leptin in human physiology and pathophysiology—emerging clinical applications},
  author={Aoife M Brennan and Christos S. Mantzoros},
  journal={Nature Clinical Practice Endocrinology \&Metabolism},
  year={2006},
  volume={2},
  pages={318-327}
}
  • A. Brennan, C. Mantzoros
  • Published 1 June 2006
  • Biology, Medicine
  • Nature Clinical Practice Endocrinology &Metabolism
Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to… 
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TLDR
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References

SHOWING 1-10 OF 83 REFERENCES
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency.
The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple
Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults.
TLDR
Leptin replacement therapy in leptin-deficient adults with established morbid obesity results in profound weight loss, increased physical activity, changes in endocrine function and metabolism, including resolution of type 2 diabetes mellitus and hypogonadism, and beneficial effects on ingestive and noningestive behavior.
The Role of Leptin in Human Obesity and Disease: A Review of Current Evidence
  • C. Mantzoros
  • Biology, Medicine
    Annals of Internal Medicine
  • 1999
TLDR
The current understanding of leptin's role in various physiologic and pathophysiologic states in humans is presented and the potential therapeutic implications of the authors' advancing knowledge on energy homeostasis and body weight regulation are discussed.
Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy.
TLDR
Leptin replacement improved menstrual abnormalities and low E2 levels and corrected the attenuated LH response to LHRH in a group of young women with lipodystrophy and leptin deficiency, adding to the growing body of evidence that metabolic signals such as leptin play a role in neuroendocrine regulation.
Role of leptin in the neuroendocrine response to fasting
TLDR
It is proposed that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin, and preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starve-induced delay in ovulation in female mice.
Long-term efficacy of leptin replacement in patients with generalized lipodystrophy.
TLDR
R-metHuLeptin led to significant and sustained improvements in glycemia, dyslipidemia, and hepatic steatosis and represents the first novel, effective, long-term treatment for severe forms of lipodystrophy.
Effects of recombinant leptin therapy in a child with congenital leptin deficiency.
TLDR
The administration of leptin corrects their obesity by reducing their food intake and increasing their energy expenditure and these mice also have hyperinsulinemia, corticosterone excess, and infertility, which also are reversed by treatment with leptin.
Recombinant methionyl human leptin administration to achieve high physiologic or pharmacologic leptin levels does not alter circulating inflammatory marker levels in humans with leptin sufficiency or excess.
TLDR
Three interventional studies involving administration of recombinant methionyl human leptin to lean, otherwise healthy obese, and obese diabetic subjects investigate whether increasing circulating leptin levels over a wide spectrum of values would alter serum levels of inflammatory markers and other cytokines important in the T helper cell response.
Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance
  • A. Sahu
  • Biology
    Frontiers in Neuroendocrinology
  • 2003
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