title: Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.
abstract: The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin.
authors.affiliation: Department of Human Sciences, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: DiSilvestro
authors.affiliation: Department of Human Sciences, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Melgar-Bermudez
authors.affiliation: Department of Human Sciences, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Rumana
authors.initials: R
authors.lastname: Yasmeen
authors.affiliation: Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fadda
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Kalyanasundaram
authors.affiliation: Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Chen L
authors.initials: CL
authors.lastname: Gilor
authors.affiliation: Department of Human Sciences, The Ohio State University, Columbus, Ohio, 43210, United States of America.
authors.forename: Ouliana
authors.initials: O
authors.lastname: Ziouzenkova
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D052243:Resistin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D052243:Resistin