Insulin sensing by astrocytes is critical for normal thermogenesis and body temperature regulation

in Journal of Endocrinology
Authors:
Iyad H Manaserh Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA
Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

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Emily Maly Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

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Marziyeh Jahromi Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

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Lakshmikanth Chikkamenahalli Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

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Joshua Park Department of Neuroscience, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

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Jennifer Hill Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA
Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

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Correspondence should be addressed to J W Hill: JenniferW.Hill@utoledo.edu
DOI:
https://doi.org/10.1530/JOE-20-0052
Volume/Issue:
Volume 247: Issue 1
Article Type:
Research Article
Page Range:
39–52
Online Publication Date:
Oct 2020
Copyright:
© 2020 Society for Endocrinology 2020
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The important role of astrocytes in the central control of energy balance and glucose homeostasis has recently been recognized. Changes in thermoregulation can lead to metabolic dysregulation, but the role of astrocytes in this process is not yet clear. Therefore, we generated mice congenitally lacking insulin receptors (Ir) in astrocytes (IrKOGFAP mice) to investigate the involvement of astrocyte insulin signaling. IrKOGFAP mice displayed significantly lower energy expenditure and a strikingly lower basal and fasting body temperature. When exposed to cold, however, they were able to mount a thermogenic response. IrKOGFAP mice displayed sex differences in metabolic function and thermogenesis that may contribute to the development of obesity and type II diabetes as early as 2 months of age. While brown adipose tissue exhibited higher adipocyte size in both sexes, more apoptosis was seen in IrKOGFAP males. Less innervation and lower BAR3 expression levels were also observed in IrKOGFAP brown adipose tissue. These effects have not been reported in models of astrocyte Ir deletion in adulthood. In contrast, body weight and glucose regulatory defects phenocopied such models. These findings identify a novel role for astrocyte insulin signaling in the development of normal body temperature control and sympathetic activation of BAT. Targeting insulin signaling in astrocytes has the potential to serve as a novel target for increasing energy expenditure.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
14
Article Type:
Research Article
Received Date:
03 Jul 2020
Accepted Date:
13 Jul 2020
Print Publication Date:
01 Oct 2020
Online Publication Date:
Oct 2020
Keywords:
astrocytic insulin signaling; body temperature; systemic metabolism; B3-adrenergic signaling

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