title: Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.
abstract: Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life.
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands.
authors.forename: Ilse A C
authors.initials: IA
authors.lastname: Arnoldussen
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands; Department of Geriatric Medicine, Radboud university medical center, 6595 CG, Nijmegen, the Netherlands.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Wiesmann
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands.
authors.forename: Rikko H J
authors.initials: RH
authors.lastname: Noordman
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Bolijn
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands.
authors.forename: Martina P C
authors.initials: MP
authors.lastname: Mutsaers
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands.
authors.forename: Pieter J W C
authors.initials: PJ
authors.lastname: Dederen
authors.affiliation: TNO Metabolic Health Research, 2333 CK, Leiden, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.affiliation: TNO Metabolic Health Research, 2333 CK, Leiden, the Netherlands.
authors.forename: Teake
authors.initials: T
authors.lastname: Kooistra
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, 6545 CJ, Nijmegen, the Netherlands.
authors.forename: Eric A F
authors.initials: EA
authors.lastname: van Tol
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, 6545 CJ, Nijmegen, the Netherlands.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gross
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, 6545 CJ, Nijmegen, the Netherlands.
authors.forename: Marieke H
authors.initials: MH
authors.lastname: Schoemaker
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, 6545 CJ, Nijmegen, the Netherlands; Department of Radiology and Nuclear Medicins, Radboud university medical center, 6595 GA Nijmegen, the Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: TNO Metabolic Health Research, 2333 CK, Leiden, the Netherlands.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Wielinga
authors.affiliation: Department of Anatomy, Radboud university medical center, 6595 EZ, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 EN, Nijmegen, the Netherlands. Electronic address: Amanda.Kiliaan@Radboudumc.nl.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004032:Diet; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated
keywords: Brain structure; High-fat and high-carbohydrate diets; Long-chain polyunsaturated fatty acids; Neuroimaging; Obesity