Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging
- 271 Downloads
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.
KeywordsAging Dietary restriction AMPK Glucose transporters Cholesterol metabolism Brain
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.
- 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
- 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
- Mundt KA, Shanahan K (2010) Graff’s textbook of routine urinalysis and body fluids. Lippincott Williams & Wilkins, Philadelphia, p 237. ISBN 1582558752Google Scholar
- 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
- 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
- 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
- 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