Leptin resensitisation: a reversion of leptin-resistant states.

María F Andreoli,Mario Perello,Isin Cakir,Jose Donato

doi:10.1530/joe-18-0606

Abstract

Leptin resistance refers to states in which leptin fails to promote its anticipated effects, frequently coexisting with hyperleptinaemia. Leptin resistance is closely associated with obesity and also observed in physiological situations such as pregnancy and in seasonal animals. Leptin resensitisation refers to the reversion of leptin-resistant states and is associated with improvement in endocrine and metabolic disturbances commonly observed in obesity and a sustained decrease of plasma leptin levels, possibly below a critical threshold level. In obesity, leptin resensitisation can be achieved with treatments that reduce body adiposity and leptinaemia, or with some pharmacological compounds, while physiological leptin resistance reverts spontaneously. The restoration of leptin sensitivity could be a useful strategy to treat obesity, maintain weight loss and/or reduce the recidivism rate for weight regain after dieting. This review provides an update and discussion about reversion of leptin-resistant states and modulation of the molecular mechanisms involved in each situation.

Highlights

Obesity results from an imbalance between energy intake and energy expenditure and represents a major threat to health across the globe
Gestational leptin resistance is characterised by impaired leptin-induced pSTAT3 in the hypothalamus and likely plays a role in the adaptations observed during pregnancy, including increase in food intake and adiposity (Ladyman et al 2010)
Experimental evidence shows that leptin resistance can be reversed, at least to some extent, in several animal models of obesity (Fig. 2)

Summary

Introduction

Obesity results from an imbalance between energy intake and energy expenditure and represents a major threat to health across the globe. Chronic administration of leptin to mimic the leptinaemia kinetics observed in obesity slightly decreases energy expenditure (Ravussin et al 2014), and higher doses of leptin induce long-lasting effects that can completely deplete body fat stores in animals (Halaas et al 1997, Montez et al 2005).

Results

Conclusion