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ORIGINAL ARTICLE
Expression Profile of Brain Aging and Metabolic Function are Altered by Resveratrol or α-Ketoglutarate Supplementation in Rats Fed a High-Fat Diet
 
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Department of Animal Nutrition and Feed Sciences, National Research Institute of Animal Production, Krakowska Str. 1, 32-083 Balice, Poland
 
2
Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska Str. 1, 32-083 Balice, Poland
 
 
Submission date: 2021-04-08
 
 
Final revision date: 2021-06-15
 
 
Acceptance date: 2021-06-17
 
 
Online publication date: 2021-07-20
 
 
Publication date: 2021-07-20
 
 
Corresponding author
Paulina Szczurek-Janicka   

Department of Animal Nutrition and Feed Sciences, National Research Institute of Animal Production, Krakowska Street 1, 32-083, Balice, Poland
 
 
Pol. J. Food Nutr. Sci. 2021;71(3):255-268
 
KEYWORDS
TOPICS
ABSTRACT
The aim of this study was to examine the impact of different dietary interventions started at middle age on the metabolic phenotype and gene expression profiling in the hypothalamus. One-year old rats were fed either a control diet, high-fat diet (HFD), HFD supplemented with resveratrol (HFD+RESV), or HFD supplemented with α-ketoglutarate (HFD+AKG). A 6-week HFD feeding led to significant changes in concentrations of plasma glucose, insulin, lipids, and thyroid hormones. Moreover, 32% of the 84 analyzed genes correlated with aging were differentially expressed compared to the control group, with the largest functional class being related to inflammatory response. Dietary RESV ameliorated the changes in plasma glucose, total cholesterol, and triiodothyronine concentrations induced by HFD feeding and significantly downregulated 60% of the surveyed genes compared to the control group, resulting in a major molecular shift compared to HFD alone. In contrast, AKG supplementation did not affect the metabolic phenotype, but prevented the gene expression pattern caused by HFD consumption, mimicking the effects observed in the control group. HFD feeding induces metabolic dysfunction and age-related genetic alterations in the hypothalamus of middle-aged rats, while dietary RESV or AKG may partially retard these effects, even though these compounds act in a different and specific manner.
ABBREVIATIONS
AKG – α-ketoglutarate, AUC – area under the curve, BW – body weight, HDL – high-density lipoproteins, HFD – high-fat diet, LDL – low-density lipoproteins, NPY – neuropeptide Y, RESV – resveratrol, rT3 – reverse triiodothyronine, SD – standard deviation, T3 – triiodothyronine, T4 – thyroxine, TG – triacylglycerols
FUNDING
The authors received no specific funding for the study.
 
REFERENCES (44)
1.
Andersen, G., Burkon, A., Sulzmaier, F.J., Walker, J.M., Leckband, G., Fuhst, R., Erbersdobler, H.F., Somoza, V. (2011). High dose of dietary resveratrol enhances insulin sensitivity in healthy rats but does not lead to metabolite concentrations effective for SIRT1 expression. Molecular Nutrition & Food Research, 55(8), 1197-1206. https://doi.org/10.1002/mnfr.2....
 
2.
Anderson, R.M., Weindruch, R. (2010). Metabolic reprogramming, caloric restriction and aging. Trends in Endocrinology & Metabolism, 21(3), 134-141. https://doi.org/10.1016/j.tem.....
 
3.
AOAC International. (2000). Official Methods of Analysis of the Association of Official Analytical Chemists. 17th ed. Gaithersburg, MD, USA.
 
4.
Barger, J.L., Kayo, T., Vann, J.M., Arias, E.B., Wang, J., Hacker, T.A., Wang, Y., Raederstorff, D., Morrow, J.D., Leewenburgh, C., Allison, D.B., Saupe, K.W., Cartee, G.D., Weindruch, R., Prolla, T.A. (2008). A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PloS One, 3(6), art. no. e2264. https://doi.org/10.1371/annota....
 
5.
Baur, J.A., Pearson, K.J., Price, N.L., Jamieson, H.A., Lerin, C., Kalra, A., Prabhu, V.V., Allard, J.S., Lopez-Lluch, G., Lewis, K., Pistell, P.J., Poosala, S., Becker, K.G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K.W., Spencer, R.G., Lakatta, W.G., Le Couteur, D., Shaw, R.J., Navas, P., Puigserver, P., Ingram, D.K., de Cabo, R., Sinclair, D.A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 444, 337-342. https://doi.org/10.1038/nature....
 
6.
Berchtold, N.C., Cribbs, D.H., Coleman, P.D., Rogers, J., Head, E., Kim, R., Beach, T., Miller, C., Troncoso, J., Trojanowski, J.Q., Zielke, R.H., Cotman, C.W. (2008). Gene expression changes in the course of normal brain aging are sexually dimorphic. Proceedings of National Academy of Sciences, 105(40), 15605-15610. https://doi.org/10.1073/pnas.0....
 
7.
Boisvert, M.M., Erikson, G.A., Shokhirev, M.N., Allen, N.J. (2018). The aging astrocyte transcriptome from multiple regions of the mouse brain. Cell Reports, 22(1), 269-285. https://doi.org/10.1016/j.celr....
 
8.
Briggs, D.I., Lockie, S.H., Wu, Q., Lemus, M.B., Stark, R., Andrews, Z.B. (2013). Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner. Endocrinology, 154(2), 709-717. https://doi.org/10.1210/en.201....
 
9.
Chen, S., Bin, P., Ren, W., Gao, W., Liu, G., Yin, J., Duan, J., Li, Y., Yao, K., Huang, R., Tan, B., Yin, Y. (2017). Alpha-ketoglutarate (AKG) lowers body weight and affects intestinal innate immunity through influencing intestinal microbiota. Oncotarget, 8(24), art. no. 38184. https://doi.org/10.18632/oncot....
 
10.
Cheserek, M.J., Wu, G., Li, L., Li, L., Karangwa, E., Shi, Y., Le, G. (2016). Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity. Journal of Nutritional Biochemistry, 33, 36-44. https://doi.org/10.1016/j.jnut....
 
11.
Chin, R.M., Fu, X., Pai, M.Y., Vergnes, L., Hwang, H., Deng, G., Diep, S., Lomenick, B., Meli, V.S., Monsalve, G.C., Hu, E., Whelan, S.A., Wang, J.X., Jung, G., Solis, G.M., Fazlollahi, F., Kaweeteerawat, C., Quach, A., Nili, M., Krall, A.S., Godwin, H.A., Chang, H.R., Faull, K.F., Guo, F., Jiang, M., Trauger, S.A., Saghatelian, A., Braas, D., Christofk, H.R., Clarke, C.F., Teitell, M.A., Petrascheck, M., Reue, K., Jung, M.E., Frand, A.R., Huang, J. (2014). The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature, 510(7505), 397-401. https://doi.org/10.1038/nature....
 
12.
Cho, S.J., Jung, U.J., Choi, M.S. (2012). Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. British Journal of Nutrition, 108(12), 2166-2175. https://doi.org/10.1017/S00071....
 
13.
Dacks, P.A., Moreno, C.L., Kim, E.S., Marcellino, B.K., Mobbs, C.V. (2013). Role of the hypothalamus in mediating protective effects of dietary restriction during aging. Frontiers in Neuroendocrinology, 34(2), 95-106. https://doi.org/10.1016/j.yfrn....
 
14.
Dąbek, M., Kruszewska, D., Filip, R., Hotowy, A., Pierzynowski, Ł., Wojtasz‐Pająk, A., Szymanczyk, S., Valverdre-Piedra, J.L., Werpachowska. E., Pierzynowski, S.G. (2005). α‐Ketoglutarate (AKG) absorption from pig intestine and plasma pharmacokinetics. Journal of animal physiology and animal nutrition, 89(11‐12), 419-426. https://doi.org/10.1111/j.1439....
 
15.
De Magalhães, J.P., Curado, J., Church, G.M. (2009). Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics, 25(7), 875-881. https://doi.org/10.1093/bioinf....
 
16.
Franco, J.G., Dias-Rocha, C.P., Fernandes, T.P., Maia, L.A., Lisboa, P.C., Moura, E.G., Pazos-Moura, C.C., Trevenzoli, I.H. (2016). Resveratrol treatment rescues hyperleptinemia and improves hypothalamic leptin signaling programmed by maternal high-fat diet in rats. European Journal of Nutrition, 55(2), 601-610. https://doi.org/10.1007/s00394....
 
17.
Fraser, H.B., Khaitovich, P., Plotkin, J.B., Pääbo, S., Eisen, M.B. (2005). Aging and gene expression in the primate brain. PLoS Biology, 3(9), art. no. e274. https://doi.org/10.1371/journa....
 
18.
González-Velasco, O., Papy-García, D., Le Douaron, G., Sánchez-Santos, J.M., De Las Rivas, J. (2020). Transcriptomic landscape, gene signatures and regulatory profile of aging in the human brain. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 1863(6), art no. 194491. https://doi.org/10.1016/j.bbag....
 
19.
Jimoh, A., Tanko, Y., Ayo, J.O., Ahmed, A., Mohammed, A. (2018). Resveratrol increases serum adiponectin level and decreases leptin and insulin level in an experimental model of hypercholesterolemia. Pathophysiology, 25(4), 411-417. https://doi.org/10.1016/j.path....
 
20.
Kandhare, A.D., Bandyopadhyay, D., Thakurdesai, P.A. (2018). Low molecular weight galactomannans-based standardized fenugreek seed extract ameliorates high-fat diet-induced obesity in mice via modulation of FASn, IL-6, leptin, and TRIP-Br2. RSC Advances, 8(57), 32401-32416. https://doi.org/10.1039/C8RA05....
 
21.
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., Geny, B., Laakso, M., Puigserver, P., Auwex, J. (2006). Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell, 127, 1109-1122. https://doi.org/10.1016/j.cell....
 
22.
Lizarbe, B., Cherix, A., Duarte, J.M., Cardinaux, J.R., Gruetter, R. (2019). High-fat diet consumption alters energy metabolism in the mouse hypothalamus. International Journal of Obesity, 43(6), 1295-1304. https://doi.org/10.1038/s41366....
 
23.
Miura, D., Miura, Y., Yagasaki, K. (2003). Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats. Life Science, 73(11), 1393-1400. https://doi.org/10.1016/S0024-....
 
24.
Mohamed, I.A., Zaki, N.A., Walaa, A.M. (2010). Alterations in insulin, leptin, orexin-A and neuropeptide-Y levels in the high-fat diet fed rats. Australian Journal of Basic and Applied Sciences, 4(6), 1473-1481.
 
25.
Mohan, A., Mather, K.A., Thalamuthu, A., Baune, B.T., Sachdev, P.S. (2016). Gene expression in the aging human brain: an overview. Current Opinion in Psychiatry, 29(2), 159-167. https://doi.org/10.1097/YCO.00....
 
26.
Morrison, C.D., Pistell, P.J., Ingram, D.K., Johnson, W.D., Liu, Y., Fernandez‐Kim, S.O., White, C.L., Purpera, M.N., Uranga, R.M., Bruce-Keller, A.J., Keller, J.N. (2010). High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling. Journal of Neurochemistry, 114(6), 1581-1589. https://doi.org/10.1111/j.1471....
 
27.
Müller, R.H., Radtke, M., Wissing, S.A. (2002). Nanostructured lipid matrices for improved microencapsulation of drugs. International Journal of Pharmaceutics, 242(1-2), 121-128. https://doi.org/10.1016/S0378-....
 
28.
Niemiec, T., Sikorska, J., Harrison, A., Szmidt, M., Sawosz, E., Wirth-Dzieciolowska, E., Wilczak, J., Pierzynowski, S. (2011). Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice. Journal of Physiology and Pharmacology, 62(1), art. no. 37.
 
29.
Noris, M., Remuzzi, G. (2013). Overview of complement activation and regulation. Seminars in Nephrology, 33(6), 479-492. https://doi.org/10.1016/j.semn....
 
30.
NRC. (1995). Nutrient requirement of laboratory animals. In: National Research Council (US) Subcommittee on Laboratory Animal Nutrition. National Academies Press (US), Washington (DC), USA.
 
31.
Nuthikattu, S., Milenkovic, D., Rutledge, J., Villablanca, A. (2019). The western diet regulates hippocampal microvascular gene expression: an integrated genomic analyses in female mice. Scientific Reports, 9(1), art. no. 19058. https://doi.org/10.1038/s41598....
 
32.
Radzki, R.P., Bienko, M., Pierzynowski, S.G. (2009). Effect of dietary alpha-ketoglutarate on blood lipid profile during hypercholesterolaemia in rats. Scandinavian Journal of Clinical and Laboratory Investigation, 69(2), 175-180. https://doi.org/10.1080/003655....
 
33.
Salminen, A., Kaarniranta, K., Hiltunen, M., Kauppinen, A. (2014). Krebs cycle dysfunction shapes epigenetic landscape of chromatin: Novel insights into mitochondrial regulation of aging process. Cell Signal, 26(7), 1598-1603. https://doi.org/10.1016/j.cell....
 
34.
Testa, G., Biasi, F., Poli, G., Chiarpotto, E. (2014). Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Current Pharmaceutical Design, 20(18), 2950-2977. https://doi.org/10.2174/138161....
 
35.
Tian, Q., Zhao, J., Yang, Q., Wang, B., Deavila, J.M., Zhu, M.J., Du, M. (2020). Dietary alpha‐ketoglutarate promotes beige adipogenesis and prevents obesity in middle‐aged mice. Aging Cell, 19(1), art. no. e13059. https://doi.org/10.1111/acel.1....
 
36.
Thomas, S.C., Alhasawi, A., Appanna, V.P., Auger, C., Appanna, V.D. (2015). Brain metabolism and Alzheimer’s disease: The prospect of a metabolite-based therapy. Journal of Nutrition, Health and Aging, 19(1), 58-63. https://doi.org/10.1007/s12603....
 
37.
Uranga, R.M., Bruce‐Keller, A.J., Morrison, C.D., Fernandez‐Kim, S.O., Ebenezer, P.J., Zhang, L., Dasuri, K., Keller, J.N. (2010). Intersection between metabolic dysfunction, high fat diet consumption, and brain aging. Journal of Neurochemistry, 114, 344-361. https://doi.org/10.1111/j.1471....
 
38.
Walle, T., Hsieh, F., DeLegge, M.H., Oatis, J.E., Walle, U.K. (2004). High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism & Disposition, 32(12), 1377-1382. https://doi.org/10.1124/dmd.10....
 
39.
Weindruch, R., Kayo, T., Lee, C.K., Prolla, T.A. (2002). Gene expression profiling of aging using DNA microarrays. Mechanisms of Ageing and Development, 123(2-3), 177-193. https://doi.org/10.1016/S0047-....
 
40.
Xie, Z., Li, H., Wang, K., Lin, J., Wang, Q., Zhao, G., Jia, W., Zhang, Q. (2010). Analysis of transcriptome and metabolome profiles alterations in fatty liver induced by high-fat diet in rat. Metabolism, 59(4), 554-560. https://doi.org/10.1016/j.meta....
 
41.
Ximerakis, M., Lipnick, S.L., Innes, B.T., Simmons, S.K., Adiconis, X., Dionne, DMayweather, B.A., Nguyen, L., Niziolek, Z., Ozek, C., Butty, V.L., Isserlin, R., Buchanan, S.M., Levine, S.S., Regev, A., Bader, G.D., Levin, J.Z., Rubin, L.L. (2019). Single-cell transcriptomic profiling of the aging mouse brain. Nature Neuroscience, 22(10), 1696-1708. https://doi.org/10.1038/s41593....
 
42.
XiYang, Y.B., Wang, Y.C., Zhao, Y., Ru, J., Lu, B.T., Zhang, Y.N., Wang, N.C., Hu, W.Y., Liu, J., Yang, J.W., Wang, Z.J., Hao, C.G., Feng, Z.T., Xiao, Z.C., Dong, W., Quan, X.Z., Zhang, L.F., Wang, T.H. (2016). Sodium channel voltage-gated beta 2 plays a vital role in brain aging associated with synaptic plasticity and expression of COX5A and FGF-2. Molecular Neurobiology, 53(2), 955-967. https://doi.org/10.1007/s12035....
 
43.
Zahn, J.M., Poosala, S., Owen, A.B., Ingram, D.K., Lustig, A., Carter, A., Weeraratna, A.T., Taub, D.D., Gorospe, M., Mazan-Mamczarz, K., Lakatta, E.G., Boheler, K.R., Xu, X., Mattson, M.P., Falco, G., Ko, M.S., Schlessinger, D., Firman, J., Kummerfeld, S.K., Wood, W.H., Zonderman, A.B., Kim, S.K., Becker, K.G. (2007). AGEMAP: a gene expression database for aging in mice. PLoS Genetics, 3(11), art. no. e201. https://doi.org/10.1371/journa....
 
44.
Zhou, B., Yang, L., Li, S., Huang, J., Chen, H., Hou, L., Wang, J., Green, C.D., Yan, Z., Huang, X., Kaeberein, M., Zhu, L., Xiao, H., Liu, Y., Han, J.D. (2012). Midlife gene expressions identify modulators of aging through dietary interventions. Proceedings of the National Academy of Sciences USA, 109(19), E1201-E1209. https://doi.org/10.1073/pnas.1....
 
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