Effect of restricted feeding on serum beta-hydroxybutyrate level and lipoprotein lipase expression in cerebral cortex in mice
LI Xin-hui*, ZHAN Zhi-peng, ZHANG Jing-zhu, REN Ya-hao, ZHAO Yue, AN Li
*Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, Liaoning 110122, China Corresponding author: AN Li, E-mail:anli@ cmu.edu.cn
Abstract:Objective To explore the effect of restricted feeding on the serum beta-hydroxybutyrate (βOHB) level and lipoprotein lipase (LPL) expression in cerebral cortex in mice. Methods Based on their body weight, 50 healthy adult C57BL/6J mice were randomly divided into 5 groups (each n=10), and blood was respectively collected at 0, 8, 12, 16 and 24 h after fasting for detection of serum βOHB by ELISA. Additionally, the other 20 mice were randomly divided into 2 groups (each n=10), the fasting group and control group. The mice in the fasting group received alternate-day fasting diet for 4 consecutive weeks, while those in the control group were fed ad libitum. The body weight and the percentage of body fat were measured at the end of the experiment. Moreover, the expression of LPL mRNA and protein in the cerebral cortex of mice were detected by real-time RT-PCR and Western blot respectively. Results The serum βOHB level in mice was gradually increased with the extension of fasting time, with (0.93±0.13) nmol/L, (0.95 ± 0.37) nmol/L, (1.33 ± 0.26) nmol/L, (1.68 ± 0.13) nmol/L and (1.74 ± 0.27) nmol/L at 0, 8, 12, 16 and 24 h after fasting respectively. Compared with the serum βOHB level at 0 h, the βOHB levels at 12, 16 and 24 h after fasting were significantly increased (all P<0.05). No significant difference was found between the serum βOHB levels at 16 and 24 h after fasting (P>0.05), but both were remarkably higher than that at 12 h (P<0.05). During the experiment, no abnormal manifestations were found in the mice of the alternate-day fasting group and the control group; moreover, their body weight and percentage of body fat showed no statistically significant difference (P>0.05). Compared with the control group, the expression of LPL mRNA and protein in the cerebral cortex of the mice in the alternate-day fasting group was remarkably up-regulated(P<0.01; P<0.05). Conclusions The serum βOHB level in mice is significantly increased during 12-24 h after fasting, and alternate-day fasting for 4 weeks can up-regulate the expression of LPL mRNA and protein in the cerebral cortex of mice.
[1] Shimazu T, Hirschey MD, Newman J, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor[J]. Science, 2013, 339(6116): 211-214. [2] Semenkovich CF, Chen SH, Wims M, et al. Lipoprotein lipase and hepatic lipase mRNA tissue specific expression, developmental regulation, and evolution[J]. J Lipid Res, 1989, 30(3): 423-431. [3] Xie C, Wang ZC, Liu XF, et al. Association between schizophrenia and single nucleotide polymorphisms in lipoprotein lipase gene in a Han Chinese population[J]. Psychiatr Genet, 2011, 21(6): 307-314. [4] Gong H, Dong W, Rostad SW, et al. Lipoprotein lipase (LPL) is associated with neurite pathology and its levels are markedly reduced in the dentate gyrus of Alzheimer’s disease brains[J]. J Histochem Cytochem, 2013, 61(12): 857-868. [5] Goldberg IJ, Eckel RH, Abumrad NA. Regulation of fatty acid uptake into tissues: lipoprotein lipase-and CD36-mediated pathways[J]. J Lipid Res, 2009, 50(Supplement): S86-S90. [6] Plaisance EP, Lukasova M, Offermanns S, et al. Niacin stimulates adiponectin secretion through the GPR109A receptor[J]. Am J Physiol Endocrinol Metab, 2009, 296(3): E549-E558. [7] Halberg N, Henriksen M, Sderhamn N, et al. Effect of intermittent fasting and refeeding on insulin action in healthy men[J]. J Appl Physiol, 2005, 99(6): 2128-2136. [8] Taggart AKP, Kero J, Gan X, et al. (D)-β-hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G[J]. J Biol Chem J, 2005, 280(29): 26649-26652. [9] Hatori M, Vollmers C, Zarrinpar A, et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet[J]. Cell Metab, 2012, 15(6): 848-860. [10] Anson RM, Jones B, de Cabod R. The diet restriction paradigm: a brief review of the effects of every-other-day feeding[J]. Age, 2005, 27(1): 17-25. [11] Varady KA, Hellerstein MK. Alternate-day fasting and chronic disease prevention: a review of human and animal trials[J]. Am J Clin Nutr, 2007, 86(1): 7-13. [12] Desautels M, Dulos RA. Effects of repeated cycles of fasting-refeeding on brown adipose tissue composition in mice[J]. Am J Physiol, 1988, 255(2): E120-E128. [13] Xie C, Wang ZC, Liu XF, et al. The common biological basis for common complex diseases: evidence from lipoprotein lipase gene[J]. Eur J Hum Genet 2010, 18(1): 3-7. [14] Wang H, Eckel RH. Lipoprotein lipase: from gene to obesity[J]. Am J Physiol, 2009, 297(2): E271-E288. [15] Yoshida K, Shimizugawa T, Ono M, et al. Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase[J]. J Lipid Res, 2002, 43(11): 1770-1772. [16] Lee J H, Kim KA, Kwon KB, et al. Diallyl disulfide accelerates adipogenesis in 3T3-L1 cells[J]. Int J Mol Med, 2007, 20(1): 59-64.