Effects of caloric restriction on O-GlcNAcylation, Ca(2+) signaling, and learning impairment in the hippocampus of ob/ob mice.
Diabetes may adversely affect cognitive function and, conversely, caloric restriction (CR) increases longevity and improves memory. To shed light on the unknown underlying mechanisms involved in these observations, we examined the effects of CR on serum metabolic parameters and hippocampal protein expression in the ob/ob mice model of obesity-induced diabetes. We found that CR reduced hepatic steatosis and insulin resistance in ob/ob mice. In addition, CR increased the levels of hippocampal O-linked-N-acetylglucosamine (O-GlcNAc) and GlcNAc transferase and decreased the expression of calcium/calmodulin-dependent protein kinase II, lipocalin-2, and phosphorylated tau. Furthermore, CR lessened the learning deficits that are typically seen in ob/ob mice. These findings indicate that CR may reverse obesity-related brain glucose impairment and intracellular Ca(2+) dysfunction and relieve learning impairment associated with diabetes.
Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA.
Byeong Tak
BT
Jeon
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Rok Won
RW
Heo
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Eun Ae
EA
Jeong
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Chin-Ok
CO
Yi
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Jong Youl
JY
Lee
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Kyung Eun
KE
Kim
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Hwajin
H
Kim
Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: anaroh@gnu.ac.kr.
Gu Seob
GS
Roh
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D031204:Caloric Restriction; D048909:Diabetes Complications / Q000150:complications; D005234:Fatty Liver / Q000517:prevention & control; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D007333:Insulin Resistance; D007858:Learning; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
D016875:tau Proteins; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D000117:Acetylglucosamine
Calcium homeostasis; Caloric restriction; Hippocampus; Learning impairment; O-linked-N-acetylglucosamine