GEOFFREY HARRIS PRIZE LECTURE 2018: Novel pathways regulating neuroendocrine function, energy homeostasis and metabolism in humans.

Aimilia Eirini Papathanasiou,Olivia M Farr,Eric Nolen-Doerr,Christos S Mantzoros

doi:10.1530/eje-18-0847

Aimilia Eirini Papathanasiou, Olivia M Farr + Show 2 more

Open Access

https://doi.org/10.1530/eje-18-0847

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Abstract

The discovery of leptin, an adipocyte-secreted hormone, set the stage for unraveling the mechanisms dictating energy homeostasis, revealing adipose tissue as an endocrine system that regulates appetite and body weight. Fluctuating leptin levels provide molecular signals to the brain regarding available energy reserves modulating energy homeostasis and neuroendocrine response in states of leptin deficiency and to a lesser extent in hyperleptinemic states. While leptin replacement therapy fails to provide substantial benefit in common obesity, it is an effective treatment for congenital leptin deficiency and states of acquired leptin deficiency such as lipodystrophy. Current evidence suggests that regulation of eating behavior in humans is not limited to homeostatic mechanisms and that the reward, attention, memory and emotion systems are involved, participating in a complex central nervous system network. It is critical to study these systems for the treatment of typical obesity. Although progress has been made, further studies are required to unravel the physiology, pathophysiology and neurobehavioral mechanisms underlying potential treatments for weight-related problems in humans.

Highlights

Fluctuating leptin levels provide molecular signals to the brain regarding available energy reserves modulating energy homeostasis and neuroendocrine response in states of leptin deficiency and to a lesser extent in hyperleptinemic states
We begin discussing leptin as a well-studied peripheral signal and its role in leanness before discussing typical obesity, which is a state of leptin tolerance or resistance, and the other peripheral/ central mechanisms that may be at play in regulating body weight with a focus on human physiology
We demonstrate that fluctuations in circulating leptin levels inversely relate to those in adrenocorticotropic hormone (ACTH) and cortisol in healthy men [19]

Summary

Introduction

Fluctuating leptin levels provide molecular signals to the brain regarding available energy reserves modulating energy homeostasis and neuroendocrine response in states of leptin deficiency and to a lesser extent in hyperleptinemic states. In states of acute energy deficit and/or low body fat mass or leanness, low leptin levels trigger the hypothalamus to increase appetite and decrease energy expenditure in mice [5] and in humans. We begin discussing leptin as a well-studied peripheral signal and its role in leanness before discussing typical obesity, which is a state of leptin tolerance or resistance, and the other peripheral/ central mechanisms that may be at play in regulating body weight with a focus on human physiology.

Results

Conclusion