Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life.

Jae Geun Kim,Jin Kwon Jeong,Byung Ju Lee

doi:10.3390/nu12113256

Abstract

Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.

Highlights

Leptin, one of the most extensively characterized adipokines produced mainly from the white adipose tissue, travels the entire body through the bloodstream and triggers leptin receptor-associated signaling to regulate a broad spectrum of whole body physiological homeostasis, including metabolic and cardiovascular systems
These investigations indicate the necessity for normal maternal nutritional balance and leptin level for healthy neural development and metabolic homeostasis in their offspring
Oppositely,these reduced maternal leptin levels significantly correlated with fat massweights gain [41,42]

Summary

Introduction

One of the most extensively characterized adipokines produced mainly from the white adipose tissue, travels the entire body through the bloodstream and triggers leptin receptor-associated signaling to regulate a broad spectrum of whole body physiological homeostasis, including metabolic and cardiovascular systems. Impairment in leptin signaling in early life results in the development of permanent cardiometabolic abnormality [9,10,11,12]. Both animals and humans with genetic deletions or mutations of either leptin or leptin receptor develop insulin resistance and a severe obese phenotype in postnatal life [9,10,11,12,13,14,15,16]. Recovery of leptin signaling in the postnatal period of leptin signaling-deficient animals failed to reverse most of the metabolic abnormalities, indicating the existence of developmental time-sensitive and leptin-dependent programming for cardiometabolic functioning in later life [11]. We will provide a more recent update for early (from gestation to childhood) and adulthood leptin as a predictor of future cardiovascular and metabolic fate

Maternal and Cord Leptin during Gestation

Postnatal Leptin

Merge of Leptin with Early Environmental Factors

Leptin as a Hallmark of Cardiometabolic Fate in Adulthood

Findings

Conclusions