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Yin and Yang of hypothalamic insulin and leptin signaling in regulating white adipose tissue metabolism

  • Thomas Scherer
  • Christoph Buettner
Article

Abstract

Fatty acids released from white adipose tissue (WAT) provide important energy substrates during fasting. However, uncontrolled fatty acid release from WAT during non-fasting states causes lipotoxicity and promotes inflammation and insulin resistance, which can lead to and worsen type 2 diabetes (DM2). WAT is also a source for insulin sensitizing fatty acids such as palmitoleate produced during de novo lipogenesis. Insulin and leptin are two major hormonal adiposity signals that control energy homeostasis through signaling in the central nervous system. Both hormones have been implicated to regulate both WAT lipolysis and de novo lipogenesis through the mediobasal hypothalamus (MBH) in an opposing fashion independent of their respective peripheral receptors. Here, we review the current literature on brain leptin and insulin action in regulating WAT metabolism and discuss potential mechanisms and neuro-anatomical substrates that could explain the opposing effects of central leptin and insulin. Finally, we discuss the role of impaired hypothalamic control of WAT metabolism in the pathogenesis of insulin resistance, metabolic inflexibility and type 2 diabetes.

Keywords

Adipose tissue Lipolysis De novo lipogenesis Sympathetic nervous system Brain Insulin Leptin 

Abbreviations

ARC

Arcuate nucleus of the hypothalamus

DM2

Diabetes mellitus type 2

WAT

White adipose tissue

MBH

Mediobasal hypothalamus

FFAs

Free fatty acids

TGs

Triglycerides

Agrp

Agouti-related peptide

NPY

Neuropeptide Y

Pomc

Proopiomelanocortin

SD

Sprague Dawley

Nirko

Neuronal insulin receptor knock-out

PI3K

Phosphoinositide 3 kinase

STAT

Signal transducer and activator of transcription

HSL

Hormone sensitive lipase

PVN

Paraventricular nucleus

ICV

Intracerebroventricular

Notes

Acknowledgements

This work was supported by NIH Grants DK074873, DK083568 and DK082724 and an ADA basic research award to C.B. and a European Foundation for the Study of Diabetes grant to T.S.. C.B. is the recipient of a Hirschl Award.

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Medicine and Department of NeuroscienceMount Sinai School of MedicineNew YorkUSA

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