title: The prolonged survival of fibroblasts with forced lipid catabolism in visceral fat following encapsulation in alginate-poly-L-lysine.
abstract: Although alginate-poly-L-lysine (AP(L)) encapsulation of cells producing bioactive peptides has been widely tested, it is unknown whether AP(L) supports lasting catabolic functions of encapsulated cells in adipose tissue, which are required for obesity reduction. We tested functions of AP(L)-encapsulated fibroblasts isolated from wild-type (WT) and aldehyde dehydrogenase 1a1 knockout mice (KO), which resist obesity on a high-fat (HF) diet, have a higher metabolic rate, and express increased levels of thermogenic uncoupling protein-1 (Ucp1) in their deleterious visceral fat depots compared to WT mice. To enable in vivo detection and quantification, fibroblasts were stably transfected with green-fluorescent protein. WT- or KO-containing microcapsules were injected into two visceral depots of WT mice fed an HF diet. Eighty days after transplantation, microcapsules were located in vivo using magnetic resonance imaging. KO microcapsules prevented weight gain in obese WT mice compared to a mock- and WT capsule-injected groups on an HF diet. The weight loss in KO-treated mice corresponded to lipid reduction and induction of thermogenesis in the injected visceral fat. The non-treated subcutaneous fat was not altered. Our data suggest that the AP(L) polymer supports long-term catabolic functions of genetically-modified fibroblasts, which can be potentially used for depot-specific obesity treatment.
authors.affiliation: Department of Human Nutrition, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Fangping
authors.initials: F
authors.lastname: Yang
authors.forename: Xulang
authors.initials: X
authors.lastname: Zhang
authors.forename: Andrei
authors.initials: A
authors.lastname: Maiseyeu
authors.forename: Georgeta
authors.initials: G
authors.lastname: Mihai
authors.forename: Rumana
authors.initials: R
authors.lastname: Yasmeen
authors.forename: David
authors.initials: D
authors.lastname: DiSilvestro
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Maurya
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: K Valerie
authors.initials: KV
authors.lastname: Bergdall
authors.forename: Gregg
authors.initials: G
authors.lastname: Duester
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Ouliana
authors.initials: O
authors.lastname: Ziouzenkova
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008660:Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry; D022722:Thermogenesis / Q000502:physiology*; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; C051546:alginate-polylysine-alginate; D011107:Polylysine