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Leptin pp 67-78 | Cite as

Leptin, Obesity, and Leptin Resistance

  • Heike MünzbergEmail author
  • Steven B. Heymsfield
Chapter

Abstract

The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was rather stigmatized as a condition caused by lack of character and self-control. With leptin and its receptor being the first single genes that could cause morbid obesity in man and mice, it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. Unfortunately, the high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. It is now hoped that leptin resistance can be overcome by drugs that enhance leptin sensitivity. We review current knowledge of the mechanisms that cause leptin resistance and factors that influence leptin resistance and sensitivity. This topic is further discussed in the context of how and if improvement of leptin resistance can hold the key to cure human obesity.

Keywords

Leptin receptor STAT3 SOCS3 Hypothalamus Blood–brain barrier Leptin transport Cellular leptin resistance 

Abbreviations

ob/ob mice

Leptin-deficient mice

db/db mice

Leptin receptor-deficient mice

BBB

Blood–brain barrier

LepRb

Long form leptin receptor

CSF

Cerebrospinal fluid

JAK2

Janus-kinase-2

Y985/1077/1138

Tyrosine residues 985/1077/1138

SHP-2

Src homology-2 domain protein

MAPK

Mitogen-activated-protein-kinase

STAT3/5

Signal-transducer-and-acti- vator-of transcription-3/5

pSTAT3

Phosphor-STAT3

SOCS-3

Suppressor-of-cytokine-sig-naling-3

PTP1B

Phosphotyrosine phospha tase-1B

HFD

High-fat diet

DIO

Diet-induced obesity

ARC

Arcuate nucleus

α-MSH

α-Melanocyte-stimulating hormone

AgRP

Agouti-related protein

LPS

Lipopolysaccharides

CVO

Circumventricular organ

ME

Median eminence

VMH

Ventromedial hypothalamus

ER

Endoplasmatic reticulum

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Pennington Biomedical Research Center, LSU systemBaton RougeUSA

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