Biogerontology

, Volume 19, Issue 2, pp 121–132 | Cite as

Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging

  • Kosara Smiljanic
  • Smilja Todorovic
  • Aleksandra Mladenovic Djordjevic
  • Tim Vanmierlo
  • Dieter Lütjohann
  • Sanja Ivkovic
  • Selma Kanazir
Research Article
  • 226 Downloads

Abstract

Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. We measured the impact of different DRs on the expression levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed the changes in the amounts of cholesterol, its metabolite, and precursors following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex while the increased levels were detected in the hippocampus. Glucose metabolism was more affected in the cortex, while cholesterol metabolism was more influenced in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with fewer changes compared to the cortex. We showed that LDF and IF differently affected the brain energy homeostasis during aging and that specific brain regions exhibited distinct vulnerabilities towards DRs. Consequently, special attention should be paid to the DR application among elderly as different phases of aging do not respond equally to altered nutritional regimes.

Keywords

Aging Dietary restriction AMPK Glucose transporters Cholesterol metabolism Brain 

Notes

Acknowledgements

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant ON173056; the Fogarty International Research Award, NIH (R03AG046216).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interests.

References

  1. Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci USA 100:6216–6220CrossRefPubMedPubMedCentralGoogle Scholar
  2. Apelt J, Mehlhorn G, Schliebs R (1999) Insulin-sensitive GLUT4 glucose transporters are colocalized with GLUT3-expressing cells and demonstrate a chemically distinct neuron-specific localization in rat brain. J Neurosci Res 57(5):693–705CrossRefPubMedGoogle Scholar
  3. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495CrossRefPubMedGoogle Scholar
  4. Blázquez C, Geelen MJ, Velasco G, Guzmán M (2001) The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. FEBS Lett 489(2–3):149–153CrossRefPubMedGoogle Scholar
  5. Cheng CM, Kelley B, Wang J, Strauss D, Eagles DA, Bondy CA (2003) A ketogenic diet increases brain insulin-like growth factor receptor and glucose transporter gene expression. Endocrinology 144(6):2676–2682CrossRefPubMedGoogle Scholar
  6. Coughlan KA, Balon TW, Valentine RJ, Petrocelli R, Schultz V, Brandon A, Cooney GJ, Kraegen EW, Ruderman NB, Saha AK (2015) Nutrient Excess and AMPK Downregulation in Incubated Skeletal Muscle and Muscle of Glucose Infused Rats. PLoS ONE 10(5):e0127388CrossRefPubMedPubMedCentralGoogle Scholar
  7. Couillard-Despres S, Iglseder B, Aigner L (2011) Neurogenesis, cellular plasticity and cognition: the impact of stem cells in the adult and aging brain-a mini-review. Gerontology 57(6):559–564CrossRefPubMedGoogle Scholar
  8. Craft S (2006) Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications. Alzheimer Dis Assoc Disord 20:298–301CrossRefPubMedGoogle Scholar
  9. Culmsee C, Monnig J, Kemp BE, Mattson MP (2001) AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci 17(1):45–58CrossRefPubMedGoogle Scholar
  10. Cummings SR (2007) The biology of aging. J Musculoskelet Neuronal Interact 7:340–341PubMedGoogle Scholar
  11. Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI (2011) Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition 27:3–20CrossRefPubMedGoogle Scholar
  12. Dagon Y, Avraham Y, Magen I, Gertler A, Ben-Hur T, Berry EM (2005) Nutritional status, cognition, and survival: a new role for leptin and AMP kinase. J Biol Chem 280(51):42142–42148CrossRefPubMedGoogle Scholar
  13. Dietschy JM, Turley SD (2001) Cholesterol metabolism in the brain. Curr Opin Lipidol 12(2):105–112CrossRefPubMedGoogle Scholar
  14. Duan W, Guo Z, Mattson MP (2001) Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. J Neurochem 76:619–626CrossRefPubMedGoogle Scholar
  15. Fon Tacer K, Pompon D, Rozman D (2010) Adaptation of cholesterol synthesis to fasting and TNF-alpha: profiling cholesterol intermediates in the liver, brain, and testis. J Steroid Biochem Mol Biol 121:619–625CrossRefPubMedGoogle Scholar
  16. Ha J, Guan KL, Kim J (2015) AMPK and autophagy in glucose/glycogen metabolism. Mol Aspects Med 46:46–62CrossRefPubMedGoogle Scholar
  17. Hadem IKH, Majaw T, Kharbuli B, Sharma R (2017) Beneficial effects of dietary restriction in aging brain. J Chem Neuroanat.  https://doi.org/10.1016/j.jchemneu.2017.10 PubMedGoogle Scholar
  18. Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13(4):251–262CrossRefPubMedPubMedCentralGoogle Scholar
  19. Hayakawa K, Mishima K, Nozako M, Hazekawa M, Aoyama Y, Ogata A, Harada K, Fujioka M, Abe K, Egashira N, Iwasaki K, Fujiwara M (2007) High-cholesterol feeding aggravates cerebral infarction via decreasing the CB1 receptor. Neurosci Lett 414:183–187CrossRefPubMedGoogle Scholar
  20. Hill JL, Kobori N, Zhao J, Rozas NS, Hylin MJ, Moore AN, Dash PK (2016) Traumatic brain injury decreases AMP-activated protein kinase activity and pharmacological enhancement of its activity improves cognitive outcome. J Neurochem 139(1):106–119CrossRefPubMedPubMedCentralGoogle Scholar
  21. Jansen M, Wang W, Greco D, Bellenchi GC, di Porzio U, Brown AJ, Ikonen E (2013) What dictates the accumulation of desmosterol in the developing brain? FASEB J 27(3):865–870CrossRefPubMedGoogle Scholar
  22. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1(1):15–25CrossRefPubMedGoogle Scholar
  23. Katewa SD (2009) Kapahi P (2010) Dietary restriction and aging. Aging Cell 9(2):105–112CrossRefGoogle Scholar
  24. Klein B, Kuschinsky W, Schröck H, Vetterlein F (1986) Interdependency of local capillary density, blood flow, and metabolism in rat brains. Am J Physiol 251(6 Pt 2):H1333–H1340PubMedGoogle Scholar
  25. Koranyi L, Bourey RE, James D, Mueckler M, Fiedorek FT Jr, Permutt MA (1991) Glucose transporter gene expression in rat brain: pretranslational changes associated with chronic insulin-induced hypoglycemia, fasting, and diabetes. Mol Cell Neurosci 2(3):244–252CrossRefPubMedGoogle Scholar
  26. Leino RL, Gerhart DZ, van Bueren AM, McCall AL, Drewes LR (1997) Ultrastructural localization of GLUT 1 and GLUT 3 glucose transporters in rat brain. J Neurosci Res 49(5):617–626CrossRefPubMedGoogle Scholar
  27. Lütjohann D, Brzezinka A, Barth E, Abramowski D, Staufenbiel M, von Bergmann K, Beyreuther K, Multhaup G, Bayer TA (2002) Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J Lipid Res 43:1078–1085CrossRefPubMedGoogle Scholar
  28. Martin M, Dotti CG, Ledesma MD (2010) Brain cholesterol in normal and pathological aging. Biochim Biophys Acta 1801(8):934–944CrossRefPubMedGoogle Scholar
  29. Mattson MP (2005) Energy intake, meal frequency, and health: a neurobiological perspective. Annu Rev Nutr 25:237–260CrossRefPubMedGoogle Scholar
  30. Mattson MP, Duan W, Guo Z (2003) Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. J Neurochem 84:417–431CrossRefPubMedGoogle Scholar
  31. McCall AL, Van-Bueren AM, Nipper V, Moholt-Siebert M, Downes H, Lessov N (1996) Forebrain ischemia increases GLUT1 protein in brain microvessels and parenchyma. J Cereb Blood Flow Metab 16:69–76CrossRefPubMedGoogle Scholar
  32. Mladenovic Djordjevic A, Perovic M, Tesic V, Tanic N, Lj Rakic, Ruzdijic S, Kanazir S (2010) Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. Neurochem Int 56:250–255CrossRefPubMedGoogle Scholar
  33. Mulas MF, Demuro G, Mulas C, Putzolu M, Cavallini G, Donati A, Bergamini E, Dessi S (2005) Dietary restriction counteracts age-related changes in cholesterol metabolism in the rat. Mech Ageing Dev 126:648–654CrossRefPubMedGoogle Scholar
  34. Mundt KA, Shanahan K (2010) Graff’s textbook of routine urinalysis and body fluids. Lippincott Williams & Wilkins, Philadelphia, p 237. ISBN 1582558752Google Scholar
  35. Pallottini V, Marino M, Cavallini G, Bergamini E, Trentalance A (2003) Age-related changes of isoprenoid biosynthesis in rat liver and brain. Biogerontology 4:371–378CrossRefPubMedGoogle Scholar
  36. Popp J, Meichsner S, Kölsch H, Lewczuk P, Maier W, Kornhuber J, Jessen F, Lütjohann D (2013) Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer’s disease. Biochem Pharmacol 86(1):37–42CrossRefPubMedGoogle Scholar
  37. Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S (2009) AMPK in the brain: its roles in energy balance and neuroprotection. J Neurochem 109(Suppl 1):17–23CrossRefPubMedPubMedCentralGoogle Scholar
  38. Rossi S, Zanier ER, Mauri I, Columbo A, Stocchetti N (2001) Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. J Neurol Neurosurg Psychiatry 71:448–454CrossRefPubMedPubMedCentralGoogle Scholar
  39. Scheepers A, Joost HG, Schürmann A (2004) The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function. J Parenter Enteral Nutr 28(5):364–371CrossRefGoogle Scholar
  40. Simpson IA, Vannucci SJ, DeJoseph MR, Hawkins RA (2001) Glucose transporter asymmetries in the bovine blood-brain barrier. J Biol Chem 276(16):12725–12729CrossRefPubMedGoogle Scholar
  41. Smiljanic K, Vanmierlo T, Mladenovic Djordjevic A, Perovic M, Loncarevic-Vasiljkovic N, Tesic V, Rakic L, Ruzdijic S, Lütjohann D, Kanazir S (2013) Aging induces tissue-specific changes in cholesterol metabolism in rat brain and liver. Lipids 48(11):1069–1077CrossRefPubMedGoogle Scholar
  42. Smiljanic K, Vanmierlo T, Mladenovic Djordjevic A, Perovic M, Ivkovic S, Lütjohann D, Kanazir S (2014) Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats. Age (Dordr) 36(3):9654CrossRefGoogle Scholar
  43. Smiljanic K, Pesic V, Mladenovic Djordjevic A, Pavkovic Z, Brkic M, Ruzdijic S, Kanazir S (2015) Long-term dietary restriction differentially affects the expression of BDNF and its receptors in the cortex and hippocampus of middle-aged and aged male rats. Biogerontology 16(1):71–83CrossRefPubMedGoogle Scholar
  44. Smith ME (1968) The turnover of myelin in the adult rat. Biochim Biophys Acta 164(2):285–293CrossRefPubMedGoogle Scholar
  45. Steinberg GR, Kemp BE (2009) AMPK in health and disease. Physiol Rev 89(3):1025–1078CrossRefPubMedGoogle Scholar
  46. Thorens B, Mueckler M (2010) Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab 298(2):E141–E145CrossRefPubMedGoogle Scholar
  47. Ulgherait M, Rana A, Rera M, Graniel J, Walker DW (2014) AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep 8(6):1767–1780CrossRefPubMedPubMedCentralGoogle Scholar
  48. Valenza M, Carroll JB, Leoni V, Bertram LN, Björkhem I, Singaraja RR, Di Donato S, Lütjohann D, Hayden MR, Cattaneo E (2007) Cholesterol biosynthesis pathway is disturbed in YAC128 mice and is modulated by huntingtin mutation. Hum Mol Genet 16(18):2187–2198CrossRefPubMedGoogle Scholar
  49. Vanmierlo T, Bloks VW, van Vark-van der Zee LC, Rutten K, Kerksiek A, Friedrichs S, Sijbrands E, Steinbusch HW, Kuipers F, Lütjohann D, Mulder M (2010) Alterations in brain cholesterol metabolism in the APPSLxPS1mut mouse, a model for Alzheimer’s disease. J Alzheimers Dis 19(1):117–127CrossRefPubMedGoogle Scholar
  50. Vanmierlo T, Bogie JF, Mailleux J, Vanmol J, Lütjohann D, Mulder M, Hendriks JJ (2015) Plant sterols: friend or foe in CNS disorders? Prog Lipid Res 58:26–39CrossRefPubMedGoogle Scholar
  51. Vilchez D, Ros S, Cifuentes D, Pujadas L, Vallès J, García-Fojeda B, Criado-García O, Fernández-Sánchez E, Medraño-Fernández I, Domínguez J, García-Rocha M, Soriano E, Rodríguez de Córdoba S, Guinovart JJ (2007) Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat Neurosci 10(11):1407–1413CrossRefPubMedGoogle Scholar
  52. Weisová P, Concannon CG, Devocelle M, Prehn JH, Ward MW (2009) Regulation of glucose transporter 3 surface expression by the AMP-activated protein kinase mediates tolerance to glutamate excitation in neurons. J Neurosci 29(9):2997–3008CrossRefPubMedGoogle Scholar
  53. Ximenes da Silva A, Lavialle F, Gendrot G, Guesnet P, Alessandri JM, Lavialle M (2002) Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem 81(6):1328–1337CrossRefPubMedGoogle Scholar
  54. Yeh WL, Lin CJ, Fu WM (2008) Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia. Mol Pharmacol 73(1):170–177CrossRefPubMedGoogle Scholar
  55. Yuen AW, Sander JW (2014) Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy. Epilepsy Behav 33:110–114CrossRefPubMedGoogle Scholar
  56. Zhang H, Liu B, Li T, Zhu Y, Luo G, Jiang Y, Tang F, Jian Z, Xiao Y (2018) AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia. Int J Mol Med 41:69–76PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurobiologyInstitute for Biological Research “Sinisa Stankovic”, University of BelgradeBelgradeSerbia
  2. 2.Department of Immunology and Biochemistry, Biomedical Research InstituteHasselt UniversityHasseltBelgium
  3. 3.Laboratory for Special Lipid Diagnostics/Centre Internal Medicine/UG 68, Institute of Clinical Chemistry and Clinical PharmacologyUniversity Clinics of BonnBonnGermany

Personalised recommendations