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Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.
Peptides 2015; 71:84-93P

Abstract

Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups, whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment.

Authors+Show Affiliations

Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.Division of Endocrinology & Metabolism, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea.Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea. Electronic address: smpark@hoseo.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26188171

Citation

Kang, Suna, et al. "Central Acylated Ghrelin Improves Memory Function and Hippocampal AMPK Activation and Partly Reverses the Impairment of Energy and Glucose Metabolism in Rats Infused With Β-amyloid." Peptides, vol. 71, 2015, pp. 84-93.
Kang S, Moon NR, Kim DS, et al. Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid. Peptides. 2015;71:84-93.
Kang, S., Moon, N. R., Kim, D. S., Kim, S. H., & Park, S. (2015). Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid. Peptides, 71, pp. 84-93. doi:10.1016/j.peptides.2015.07.005.
Kang S, et al. Central Acylated Ghrelin Improves Memory Function and Hippocampal AMPK Activation and Partly Reverses the Impairment of Energy and Glucose Metabolism in Rats Infused With Β-amyloid. Peptides. 2015;71:84-93. PubMed PMID: 26188171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid. AU - Kang,Suna, AU - Moon,Na Rang, AU - Kim,Da Sol, AU - Kim,Sung Hoon, AU - Park,Sunmin, Y1 - 2015/07/15/ PY - 2015/03/18/received PY - 2015/06/09/revised PY - 2015/07/03/accepted PY - 2015/7/19/entrez PY - 2015/7/19/pubmed PY - 2016/6/18/medline KW - Cognitive function KW - Energy KW - Ghrelin KW - Glucose KW - Tau SP - 84 EP - 93 JF - Peptides JO - Peptides VL - 71 N2 - Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups, whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment. SN - 1873-5169 UR - https://www.unboundmedicine.com/medline/citation/26188171/Central_acylated_ghrelin_improves_memory_function_and_hippocampal_AMPK_activation_and_partly_reverses_the_impairment_of_energy_and_glucose_metabolism_in_rats_infused_with_β_amyloid_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(15)00201-6 DB - PRIME DP - Unbound Medicine ER -