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Leptin, Obesity, and Leptin Resistance

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Leptin

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.

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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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  1. Pennington Biomedical Research Center, LSU system, 6400 Perkins Road, Baton Rouge, LA, 70808, USA

    Heike Münzberg Ph.D. & Steven B. Heymsfield M.D.

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  1. Heike Münzberg Ph.D.
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  2. Steven B. Heymsfield M.D.
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Correspondence to Heike Münzberg Ph.D. .

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  1. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Sam Dagogo-Jack, MD

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Münzberg, H., Heymsfield, S.B. (2015). Leptin, Obesity, and Leptin Resistance. In: Dagogo-Jack, MD, S. (eds) Leptin. Springer, Cham. https://doi.org/10.1007/978-3-319-09915-6_6

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