Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat.
Interleukin-6 (IL-6) is a major cytokine involved in both normal physiological brain functions and underlying significant neuropathology. IL-6 has been suggested to play a role in the control of body weight but the results are somewhat controversial. In this study we have challenged transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice) with a high-fat diet (55% kcal from fat) versus a control diet (10%). The results demonstrate that the GFAP-IL6 mice are resistant to high-fat diet-induced increases in body weight and body fat, apparently without altering food intake and with no evidences of increased sympathetic tone. The high-fat diet-induced impaired responses to an insulin tolerance test (ITT), and to an oral glucose tolerance test (OGTT) in both genotypes. The GFAP-IL6 mice did not differ from littermate wild-type (WT) mice in ITT, but they were more glucose intolerant following the high-fat diet feeding. In summary, the present results demonstrate that brain-specific IL-6 controls body weight which may be a significant factor in physiological conditions and/or in diseases causing neuroinflammation.
Hidalgo
Juan
J
Institute of Neurosciences, Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain. Juan.Hidalgo@uab.es
Florit
Sergi
S
Giralt
Mercedes
M
Ferrer
Beatriz
B
Keller
Charlotte
C
Pilegaard
Henriette
H
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003080:Cold Temperature; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000502:physiology; D007328:Insulin / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism
D004041:Dietary Fats; D005904:Glial Fibrillary Acidic Protein; D007328:Insulin; D015850:Interleukin-6; D012313:RNA