title: Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.
abstract: Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.
authors.affiliation: Department of Pharmacology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea; Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea; Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Republic of Korea.
authors.forename: Sae Im
authors.initials: SI
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Minsuk
authors.initials: M
authors.lastname: Kim
authors.affiliation: Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Republic of Korea; Department of Microbiology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Joo Chun
authors.initials: JC
authors.lastname: Yoon
authors.affiliation: Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Republic of Korea; Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea; Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, 158-710, Republic of Korea. Electronic address: empark@ewha.ac.kr.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Park
mesh_terms: D000375:Aging; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Adipose tissue inflammation; Aging; Blood–brain barrier; Ischemic stroke; Macrophage; Microglia; Proinflammatory cytokine; Tight junction protein; Visceral fat removal