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High-Fat-Diet-Induced Weight Gain Ameliorates Bone Loss without Exacerbating AβPP Processing and Cognition in Female APP/PS1 Mice.

Peng Y, Liu J, Tang Y, Liu J, Han T, Han S, Li H, Hou C, Liu J, Long J - Front Cell Neurosci (2014)

Bottom Line: Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction.The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated.These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

View Article: PubMed Central - PubMed

Affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an , China.

ABSTRACT
Osteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer's disease (AD) than the age-matched non-dementia individuals. Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In this study, feeding a high-fat diet (HFD, 45% calorie from fat) to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning, and memory performance of the transgenic mice measured by T maze and Morris water maze, compared with the mice fed a normal-fat diet (10% calorie from fat). In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

No MeSH data available.


Related in: MedlinePlus

Soluble Aβ level and brain insulin signaling. Aβ40(A), and Aβ42(B) levels were much higher in APP/PS1 and APP/PS1 + HFD mice compared with that those of C57BL/6 mice, and the Aβ40 and Aβ42 levels were determined to be the same between APP/PS1 and APP/PS1 + HFD mice by ELISA. The expression of AβPP, Aβ tetramer, Aβ dimer (C), phosphorylation of AKT, and phosphorylation of GSK3β (G) in brain tissue were analyzed by western blot. Quantification of western blot of AβPP (D), Aβ tetramer (E), Aβ dimer (F), p-AKT (H), and p-GSK3β (I). Data were means ± SEM. n = 7 for C57BL/6 mice, n = 9 for APP/PS1 mice, and n = 8 for APP/PS1 + HFD mice. The results were analyzed by one-way ANOVA, followed by Newman–Keuls post hoc test. ***p < 0.001.
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Figure 3: Soluble Aβ level and brain insulin signaling. Aβ40(A), and Aβ42(B) levels were much higher in APP/PS1 and APP/PS1 + HFD mice compared with that those of C57BL/6 mice, and the Aβ40 and Aβ42 levels were determined to be the same between APP/PS1 and APP/PS1 + HFD mice by ELISA. The expression of AβPP, Aβ tetramer, Aβ dimer (C), phosphorylation of AKT, and phosphorylation of GSK3β (G) in brain tissue were analyzed by western blot. Quantification of western blot of AβPP (D), Aβ tetramer (E), Aβ dimer (F), p-AKT (H), and p-GSK3β (I). Data were means ± SEM. n = 7 for C57BL/6 mice, n = 9 for APP/PS1 mice, and n = 8 for APP/PS1 + HFD mice. The results were analyzed by one-way ANOVA, followed by Newman–Keuls post hoc test. ***p < 0.001.

Mentions: Neuronal insulin resistance has been confirmed in the brain of AD (Talbot et al., 2012). The neuronal insulin acts through a similar tyrosine kinase pathway as peripheral insulin acts. Insulin binds to insulin receptor (IR) followed by phosphorylation of phosphatidylinositol 3-kinase (PI3K), which leads to AKT/protein kinase B (PKB) phosphorylation and activation, and then glycogen synthesis kinase 3 (GSK3) is phosphorylated and inactivated (El Khoury et al., 2014). HFD feeding is linked to cognitive impairment mediated by brain insulin resistance and accelerated Aβ generation (Ho et al., 2004; McNeilly et al., 2011). The neural levels of p-AKT and p-GSK3 were determined in this study to evaluate the brain insulin signaling. The Aβ levels were also measured in APP/PS1 mice fed HFD (Figures 3A–I).


High-Fat-Diet-Induced Weight Gain Ameliorates Bone Loss without Exacerbating AβPP Processing and Cognition in Female APP/PS1 Mice.

Peng Y, Liu J, Tang Y, Liu J, Han T, Han S, Li H, Hou C, Liu J, Long J - Front Cell Neurosci (2014)

Soluble Aβ level and brain insulin signaling. Aβ40(A), and Aβ42(B) levels were much higher in APP/PS1 and APP/PS1 + HFD mice compared with that those of C57BL/6 mice, and the Aβ40 and Aβ42 levels were determined to be the same between APP/PS1 and APP/PS1 + HFD mice by ELISA. The expression of AβPP, Aβ tetramer, Aβ dimer (C), phosphorylation of AKT, and phosphorylation of GSK3β (G) in brain tissue were analyzed by western blot. Quantification of western blot of AβPP (D), Aβ tetramer (E), Aβ dimer (F), p-AKT (H), and p-GSK3β (I). Data were means ± SEM. n = 7 for C57BL/6 mice, n = 9 for APP/PS1 mice, and n = 8 for APP/PS1 + HFD mice. The results were analyzed by one-way ANOVA, followed by Newman–Keuls post hoc test. ***p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125950&req=5

Figure 3: Soluble Aβ level and brain insulin signaling. Aβ40(A), and Aβ42(B) levels were much higher in APP/PS1 and APP/PS1 + HFD mice compared with that those of C57BL/6 mice, and the Aβ40 and Aβ42 levels were determined to be the same between APP/PS1 and APP/PS1 + HFD mice by ELISA. The expression of AβPP, Aβ tetramer, Aβ dimer (C), phosphorylation of AKT, and phosphorylation of GSK3β (G) in brain tissue were analyzed by western blot. Quantification of western blot of AβPP (D), Aβ tetramer (E), Aβ dimer (F), p-AKT (H), and p-GSK3β (I). Data were means ± SEM. n = 7 for C57BL/6 mice, n = 9 for APP/PS1 mice, and n = 8 for APP/PS1 + HFD mice. The results were analyzed by one-way ANOVA, followed by Newman–Keuls post hoc test. ***p < 0.001.
Mentions: Neuronal insulin resistance has been confirmed in the brain of AD (Talbot et al., 2012). The neuronal insulin acts through a similar tyrosine kinase pathway as peripheral insulin acts. Insulin binds to insulin receptor (IR) followed by phosphorylation of phosphatidylinositol 3-kinase (PI3K), which leads to AKT/protein kinase B (PKB) phosphorylation and activation, and then glycogen synthesis kinase 3 (GSK3) is phosphorylated and inactivated (El Khoury et al., 2014). HFD feeding is linked to cognitive impairment mediated by brain insulin resistance and accelerated Aβ generation (Ho et al., 2004; McNeilly et al., 2011). The neural levels of p-AKT and p-GSK3 were determined in this study to evaluate the brain insulin signaling. The Aβ levels were also measured in APP/PS1 mice fed HFD (Figures 3A–I).

Bottom Line: Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction.The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated.These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

View Article: PubMed Central - PubMed

Affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an , China.

ABSTRACT
Osteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer's disease (AD) than the age-matched non-dementia individuals. Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In this study, feeding a high-fat diet (HFD, 45% calorie from fat) to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning, and memory performance of the transgenic mice measured by T maze and Morris water maze, compared with the mice fed a normal-fat diet (10% calorie from fat). In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

No MeSH data available.


Related in: MedlinePlus