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

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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.

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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

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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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  1. Department of Medicine and Department of Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY, 10029-6574, USA

    Thomas Scherer & Christoph Buettner

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Scherer, T., Buettner, C. Yin and Yang of hypothalamic insulin and leptin signaling in regulating white adipose tissue metabolism. Rev Endocr Metab Disord 12, 235–243 (2011). https://doi.org/10.1007/s11154-011-9190-4

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  • DOI: https://doi.org/10.1007/s11154-011-9190-4

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