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Obesity and Hepatic Steatosis Are Associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice.

Shie FS, Shiao YJ, Yeh CW, Lin CH, Tzeng TT, Hsu HC, Huang FL, Tsay HJ, Liu HK - PLoS ONE (2015)

Bottom Line: For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity.In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis.Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan, ROC.

ABSTRACT
Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ) in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.

No MeSH data available.


Related in: MedlinePlus

Characterization of obese conditions among each experimental group.WT or AD transgenic mice were treated with NCD or HFSTZ (A) Body weights were recorded by week. (B) Epididymal fat tissue was collected, fat mass estimation based on the percentage of epididymal fat of total body weight at after 11 weeks of dietary manipulations. (C) Representative histological microphotographs of HE-stained epididymal fat sections (scale bar, 50 μm). Adipocyte size was measured by ImageJ. (D) Serum leptin and (E) free fatty acid were quantified by ELISA after 11 weeks of dietary manipulation. Bars represent the mean ± SEM of at least three independent experiments. Experimental groups labeled with different letters are significantly different from each other (p < 0.05).
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pone.0134531.g002: Characterization of obese conditions among each experimental group.WT or AD transgenic mice were treated with NCD or HFSTZ (A) Body weights were recorded by week. (B) Epididymal fat tissue was collected, fat mass estimation based on the percentage of epididymal fat of total body weight at after 11 weeks of dietary manipulations. (C) Representative histological microphotographs of HE-stained epididymal fat sections (scale bar, 50 μm). Adipocyte size was measured by ImageJ. (D) Serum leptin and (E) free fatty acid were quantified by ELISA after 11 weeks of dietary manipulation. Bars represent the mean ± SEM of at least three independent experiments. Experimental groups labeled with different letters are significantly different from each other (p < 0.05).

Mentions: As shown in Fig 2A, the initial body weights of WT and AD mice were not different prior to the dietary manipulations. However, during the 11 weeks of the experiment, body weight gain in HFSTZ AD mice was significantly higher than that of HFSTZ WT mice. In contrast, there was no difference in body weight gain between NCD WT and NCD AD mice. The ratio of epididymal fat weight to body weight was significantly increased in HFSTZ WT and HFSTZ AD mice compared with NCD WT and AD mice at the end of experiment (Fig 2B). The mean size of adipocytes in HFSTZ AD mice was significantly enlarged compared with that of the other groups (Fig 2C).


Obesity and Hepatic Steatosis Are Associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice.

Shie FS, Shiao YJ, Yeh CW, Lin CH, Tzeng TT, Hsu HC, Huang FL, Tsay HJ, Liu HK - PLoS ONE (2015)

Characterization of obese conditions among each experimental group.WT or AD transgenic mice were treated with NCD or HFSTZ (A) Body weights were recorded by week. (B) Epididymal fat tissue was collected, fat mass estimation based on the percentage of epididymal fat of total body weight at after 11 weeks of dietary manipulations. (C) Representative histological microphotographs of HE-stained epididymal fat sections (scale bar, 50 μm). Adipocyte size was measured by ImageJ. (D) Serum leptin and (E) free fatty acid were quantified by ELISA after 11 weeks of dietary manipulation. Bars represent the mean ± SEM of at least three independent experiments. Experimental groups labeled with different letters are significantly different from each other (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526466&req=5

pone.0134531.g002: Characterization of obese conditions among each experimental group.WT or AD transgenic mice were treated with NCD or HFSTZ (A) Body weights were recorded by week. (B) Epididymal fat tissue was collected, fat mass estimation based on the percentage of epididymal fat of total body weight at after 11 weeks of dietary manipulations. (C) Representative histological microphotographs of HE-stained epididymal fat sections (scale bar, 50 μm). Adipocyte size was measured by ImageJ. (D) Serum leptin and (E) free fatty acid were quantified by ELISA after 11 weeks of dietary manipulation. Bars represent the mean ± SEM of at least three independent experiments. Experimental groups labeled with different letters are significantly different from each other (p < 0.05).
Mentions: As shown in Fig 2A, the initial body weights of WT and AD mice were not different prior to the dietary manipulations. However, during the 11 weeks of the experiment, body weight gain in HFSTZ AD mice was significantly higher than that of HFSTZ WT mice. In contrast, there was no difference in body weight gain between NCD WT and NCD AD mice. The ratio of epididymal fat weight to body weight was significantly increased in HFSTZ WT and HFSTZ AD mice compared with NCD WT and AD mice at the end of experiment (Fig 2B). The mean size of adipocytes in HFSTZ AD mice was significantly enlarged compared with that of the other groups (Fig 2C).

Bottom Line: For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity.In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis.Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan, ROC.

ABSTRACT
Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ) in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.

No MeSH data available.


Related in: MedlinePlus