When Leptin Is Not There: A Review of What Nonsyndromic Monogenic Obesity Cases Tell Us and the Benefits of Exogenous Leptin.

Kaio Cezar Rodrigues Salum,João Regis Ivar Carneiro,Cicero Brasileiro Mello,Ana Carolina Proença Da Fonseca,Verônica Marques Zembrzuski,Clarissa Menezes Maya-Monteiro,Fabiana Barzotto Kohlrausch,Jônatas De Mendonça Rolando,Patrícia Torres Bozza

doi:10.3389/fendo.2021.722441

Abstract

Obesity is a pandemic condition of complex etiology, resulting from the increasing exposition to obesogenic environmental factors combined with genetic susceptibility. In the past two decades, advances in genetic research identified variants of the leptin-melanocortin pathway coding for genes, which are related to the potentiation of satiety and hunger, immune system, and fertility. Here, we review cases of congenital leptin deficiency and the possible beneficial effects of leptin replacement therapy. In summary, the cases presented here show clinical phenotypes of disrupted bodily energy homeostasis, biochemical and hormonal disorders, and abnormal immune response. Some phenotypes can be partially reversed by exogenous administration of leptin. With this review, we aim to contribute to the understanding of leptin gene mutations as targets for obesity diagnostics and treatment strategies.

Highlights

ObesityThe equilibrium between the amount of energy intake and expenditure is the key to fat tissue homeostasis
Homozygous Lep and its human homolog gene (LEP) autosomal recessive mutations are correlated to the expression of disease phenotypes including hyperphagia, hyperinsulinemia, immune system dysfunction, and infertility
Since the description of the first monogenic variant, a total of 17 mutations in 67 cases were reported in the literature, with the majority reported from highly consanguineous families [20, 27, 77]

Summary

Introduction

The equilibrium between the amount of energy intake and expenditure is the key to fat tissue homeostasis. Such an equation is not that simple as it seems. The global obesity prevalence is greater than the underweight prevalence [2]. 107.7 million children and 603.7 million adults presented with obesity in 2015. In this same year, high body mass index (BMI) was associated with 4 million deaths [3]. It was estimated that obesity and overweight will affect 57.8% of the global adult population in 2030 [4]

Objectives

Findings

Conclusion