Increased food intake leads to obesity and insulin resistance in the tg2576 Alzheimer's disease mouse model.
Recent studies suggest that hyperinsulinemia and insulin resistance are linked to Alzheimer's disease (AD). In this study, we used Tg2576 transgenic (Tg) mice, a widely used transgenic mouse model for AD, to explore the relationship between increased amyloid beta-peptide (Abeta) and insulin resistance. When fed a high-fat diet (HFD), Tg mice developed obesity and insulin resistance at 16 wk of age. Furthermore, HFD-fed Tg mice displayed abnormal feeding behavior and increased caloric intake with time. Although caloric intake of HFD-fed Tg mice was similar to that of normal diet-fed Tg or wild-type mice during 4 to 8 wk of age, it increased sharply at 12 wk, and went up further at 16 wk, which paralleled changes in the level of Abeta40 and Abeta42 in the brain of these mice. Limiting food intake in HFD-fed Tg mice by pair-feeding a caloric intake identical with that of normal diet-fed mice completely prevented the obesity and insulin intolerance of HFD-fed Tg mice. The hypothalamus of HFD-fed Tg mice had a significant decrease in the expression of the anorexigenic neuropeptide, brain-derived neurotrophic factor, at both the mRNA and protein levels. These findings suggest that the increased Abeta in the brain of HFD-fed Tg2576 mice is associated with reduced brain-derived neurotrophic factor expression, which led to abnormal feeding behavior and increased food intake, resulting in obesity and insulin resistance in these animals.
Kohjima
Motoyuki
M
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Sun
Yuxiang
Y
Chan
Lawrence
L
D000273:Adipose Tissue / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology*; D002149:Energy Intake / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D054439:Ghrelin / Q000097:blood; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012528:Satiety Response / Q000502:physiology; D013997:Time Factors
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D004041:Dietary Fats; D054439:Ghrelin; D020738:Leptin; D012333:RNA, Messenger