Interleukin-6 contributes to early fasting-induced free fatty acid mobilization in mice.
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.
Department of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland;
Stephan
S
Wueest
Department of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland;
Flurin
F
Item
Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland;
Christina N
CN
Boyle
Division of Surgical Research, University Hospital Zurich, Zurich Switzerland;
Paulin
P
Jirkof
Division of Surgical Research, University Hospital Zurich, Zurich Switzerland;
Nikola
N
Cesarovic
Division of Endocrinology, Diabetes & Metabolism and Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland;
Helga
H
Ellingsgaard
Division of Endocrinology, Diabetes & Metabolism and Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland;
Marianne
M
Böni-Schnetzler
Division of Endocrinology, Diabetes & Metabolism and Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland;
Katharina
K
Timper
Division of Surgical Research, University Hospital Zurich, Zurich Switzerland;
Margarete
M
Arras
Division of Endocrinology, Diabetes & Metabolism and Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland;
Marc Y
MY
Donath
Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; and Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland.
Thomas A
TA
Lutz
Department of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland;
Eugen J
EJ
Schoenle
Department of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; and daniel.konrad@kispi.uzh.ch.
Daniel
D
Konrad
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000523:psychology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal
D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6
energy supply; lipolysis; metabolic adaptation