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β-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies

β-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies
β-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies

UNLABELLED: Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta-adrenergic regulation of IL-6 release in a combination of studies on humans and animals in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline [4 M:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta(1) agonist), clenbuterol (beta(2)), CL316243 (beta(3)), or saline placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo.

IN VITRO STUDIES: In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta 2/beta 3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.

Adipocytes, Adipose Tissue, Adrenergic alpha-Agonists, Adrenergic beta-Agonists, Adult, Animals, Clenbuterol, Dioxoles, Dobutamine, Female, Humans, In Vitro Techniques, Interleukin-6, Isoproterenol, Male, Mice, Mice, Inbred C57BL, Norepinephrine, Receptors, Adrenergic, beta, Journal Article, Research Support, Non-U.S. Gov't
0021-972X
5864-5869
Mohamed-Ali, V.
a681cb9a-deee-43e7-8cff-42219891ca96
Flower, L.
c51c8a7f-4bad-444e-ab9d-f2ec0f34371f
Sethi, J.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Hotamisligil, G.
59ea0e53-a259-4224-9d24-d503c4a29d15
Gray, R.
4c798da0-5d58-40a2-b1cb-f5c1144f39cb
Humphries, S.E.
3645cb7c-dbba-4027-8b08-4b4cda8a8c52
York, D.A.
bf72052a-83b4-404b-984c-2846eab86750
Pinkney, J.
412d6268-047d-4979-8586-14e3286fad48
Mohamed-Ali, V.
a681cb9a-deee-43e7-8cff-42219891ca96
Flower, L.
c51c8a7f-4bad-444e-ab9d-f2ec0f34371f
Sethi, J.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Hotamisligil, G.
59ea0e53-a259-4224-9d24-d503c4a29d15
Gray, R.
4c798da0-5d58-40a2-b1cb-f5c1144f39cb
Humphries, S.E.
3645cb7c-dbba-4027-8b08-4b4cda8a8c52
York, D.A.
bf72052a-83b4-404b-984c-2846eab86750
Pinkney, J.
412d6268-047d-4979-8586-14e3286fad48

Mohamed-Ali, V., Flower, L., Sethi, J., Hotamisligil, G., Gray, R., Humphries, S.E., York, D.A. and Pinkney, J. (2001) β-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. Journal of Clinical Endocrinology & Metabolism, 86 (12), 5864-5869. (doi:10.1210/jcem.86.12.8104).

Record type: Article

Abstract

UNLABELLED: Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta-adrenergic regulation of IL-6 release in a combination of studies on humans and animals in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline [4 M:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta(1) agonist), clenbuterol (beta(2)), CL316243 (beta(3)), or saline placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo.

IN VITRO STUDIES: In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta 2/beta 3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.

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More information

Published date: December 2001
Keywords: Adipocytes, Adipose Tissue, Adrenergic alpha-Agonists, Adrenergic beta-Agonists, Adult, Animals, Clenbuterol, Dioxoles, Dobutamine, Female, Humans, In Vitro Techniques, Interleukin-6, Isoproterenol, Male, Mice, Mice, Inbred C57BL, Norepinephrine, Receptors, Adrenergic, beta, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 418874
URI: http://eprints.soton.ac.uk/id/eprint/418874
ISSN: 0021-972X
PURE UUID: b09738b5-7900-4529-ba8e-78dae6497393
ORCID for J. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

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Date deposited: 23 Mar 2018 17:30
Last modified: 17 Dec 2019 01:27

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