Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat

TY - JOUR

T1 - Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat

AU - Hidalgo, Juan

AU - Florit, Sergi

AU - Giralt, Mercedes

AU - Ferrer, Beatriz

AU - Keller, Charlotte

AU - Pilegaard, Henriette

N1 - Keywords: Adiposity; Animals; Astrocytes; Body Composition; Body Weight; Cold Temperature; Diet; Dietary Fats; Female; Glial Fibrillary Acidic Protein; Glucose Tolerance Test; Hypothalamus; Insulin; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Promoter Regions, Genetic; RNA; Reverse Transcriptase Polymerase Chain Reaction; Sex Characteristics; Stress, Psychological

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.bbi.2009.09.002

DO - 10.1016/j.bbi.2009.09.002

M3 - Journal article

C2 - 19748567

SN - 0889-1591

VL - 24

SP - 119

EP - 126

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

IS - 1

ER -