RT Journal Article
T1 A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse
A1 López-Gambero, Antonio J.
A1 Rosell-Valle, Cristina
A1 Medina-Vera, Dina
A1 Navarro, Juan Antonio
A1 Vargas, Antonio
A1 Rivera, Patricia
A1 Sanjuan, Carlos
A1 Rodríguez de Fonseca, Fernando
A1 Suárez, Juan
K1 Alzheimer’s disease
K1 5xFAD
K1 Insulin signaling
K1 Energy expenditure
K1 Hypothalamus
K1 Neuroinflammation
K1 Ghrelin
K1 Insulin resistance
K1 Leptin
K1 Orexin
K1 Resistin
K1 STAT5 transcription factor
K1 Body weight
K1 Gastric inhibitory polypeptide
K1 Enfermedad de Alzheimer
K1 Proteínas sustrato del receptor de insulina
K1 Metabolismo energético
K1 Hipotálamo
K1 Enfermedades neuroinflamatorias
K1 Ghrelina
K1 Resistencia a la insulina
K1 Leptina
K1 Orexinas
K1 Resistina
K1 Factor de transcripción STAT5
K1 Peso corporal
K1 Polipéptido inhibidor gástrico
AB Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.
PB MDPI
SN 1661-6596
YR 2021
FD 2021-05-20
LK http://hdl.handle.net/10668/4486
UL http://hdl.handle.net/10668/4486
LA en
NO López-Gambero AJ, Rosell-Valle C, Medina-Vera D, Navarro JA, Vargas A, Rivera P, et al. A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse. Int J Mol Sci. 2021 May 20;22(10):5365
DS RISalud
RD Apr 7, 2025