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Interleukin-6 contributes to early fasting-induced free fatty acid mobilization in mice


Wueest, Stephan; Item, Flurin; Boyle, Christina N; Jirkof, Paulin; Cesarovic, Nikola; Ellingsgaard, Helga; Böni-Schnetzler, Marianne; Timper, Katharina; Arras, Margarete; Donath, Marc Y; Lutz, Thomas A; Schoenle, Eugen J; Konrad, Daniel (2014). Interleukin-6 contributes to early fasting-induced free fatty acid mobilization in mice. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 306(11):R861-R867.

Abstract

Contracting muscle releases interleukin-6 (IL-6) enabling the metabolic switch from carbohydrate to fat utilization. Similarly, metabolism is switched during transition from fed to fasting state. Herein, we examined a putative role for IL-6 in the metabolic adaptation to normal fasting. In lean C57BL/6J mice, 6 h of food withdrawal increased gene transcription levels of IL-6 in skeletal muscle but not in white adipose tissue. Concomitantly, circulating IL-6 and free fatty acid (FFA) levels were significantly increased, whereas respiratory quotient (RQ) was reduced in 6-h fasted mice. In white adipose tissue, phosphorylation of hormone-sensitive lipase (HSL) was increased on fasting, indicating increased lipolysis. Intriguingly, fasting-induced increase in circulating IL-6 levels and parallel rise in FFA concentration were absent in obese and glucose-intolerant mice. A causative role for IL-6 in the physiological adaptation to fasting was further supported by the fact that fasting-induced increase in circulating FFA levels was significantly blunted in lean IL-6 knockout (KO) and lean C57BL/6J mice treated with neutralizing IL-6 antibody. Consistently, phosphorylation of HSL was significantly reduced in adipose tissue of IL-6-depleted mice. Hence, our findings suggest a novel role for IL-6 in energy supply during early fasting.

Abstract

Contracting muscle releases interleukin-6 (IL-6) enabling the metabolic switch from carbohydrate to fat utilization. Similarly, metabolism is switched during transition from fed to fasting state. Herein, we examined a putative role for IL-6 in the metabolic adaptation to normal fasting. In lean C57BL/6J mice, 6 h of food withdrawal increased gene transcription levels of IL-6 in skeletal muscle but not in white adipose tissue. Concomitantly, circulating IL-6 and free fatty acid (FFA) levels were significantly increased, whereas respiratory quotient (RQ) was reduced in 6-h fasted mice. In white adipose tissue, phosphorylation of hormone-sensitive lipase (HSL) was increased on fasting, indicating increased lipolysis. Intriguingly, fasting-induced increase in circulating IL-6 levels and parallel rise in FFA concentration were absent in obese and glucose-intolerant mice. A causative role for IL-6 in the physiological adaptation to fasting was further supported by the fact that fasting-induced increase in circulating FFA levels was significantly blunted in lean IL-6 knockout (KO) and lean C57BL/6J mice treated with neutralizing IL-6 antibody. Consistently, phosphorylation of HSL was significantly reduced in adipose tissue of IL-6-depleted mice. Hence, our findings suggest a novel role for IL-6 in energy supply during early fasting.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
05 Vetsuisse Faculty > Institute of Laboratory Animal Science
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2 April 2014
Deposited On:17 Jun 2014 15:12
Last Modified:05 Apr 2016 17:55
Publisher:American Physiological Society
ISSN:0363-6119
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajpregu.00533.2013
PubMed ID:24694381

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