title: Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo.
abstract: Abscisic acid (ABA) is a plant hormone also present in animals, where it is involved in the regulation of innate immune cell function and of glucose disposal, through its receptor LANCL2. ABA stimulates glucose uptake by myocytes and pre-adipocytes in vitro and oral ABA improves glycemic control in rats and in healthy subjects. Here we investigated the role of the ABA/LANCL2 system in the regulation of glucose uptake and metabolism in adipocytes. Silencing of LANCL2 abrogated both the ABA- and insulin-induced increase of glucose transporter-4 expression and of glucose uptake in differentiated 3T3-L1 murine adipocytes; conversely, overexpression of LANCL2 enhanced basal, ABA- and insulin-stimulated glucose uptake. As compared with insulin, ABA treatment of adipocytes induced lower triglyceride accumulation, CO2production and glucose-derived fatty acid synthesis. ABA per se did not induce pre-adipocyte differentiation in vitro, but stimulated adipocyte remodeling in terminally differentiated cells, with a reduction in cell size, increased mitochondrial content, enhanced O2consumption, increased transcription of adiponectin and of brown adipose tissue (BAT) genes. A single dose of oral ABA (1μg/kg body weight) increased BAT glucose uptake 2-fold in treated rats compared with untreated controls. One-month-long ABA treatment at the same daily dose significantly upregulated expression of BAT markers in the WAT and in WAT-derived preadipocytes from treated mice compared with untreated controls. These results indicate a hitherto unknown role of LANCL2 in adipocyte sensitivity to insulin-stimulated glucose uptake and suggest a role for ABA in the induction and maintenance of BAT activity.
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy. Electronic address: laurasturla@unige.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Sturla
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Mannino
authors.affiliation: Department of Earth, Environment and Life Sciences, University of Genova, Via Pastore 3, 16132 Genova, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Scarfì
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Bruzzone
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Magnone
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Sociali
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Booz
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Guida
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vigliarolo
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fresia
authors.affiliation: Animal Facility, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Emionite
authors.affiliation: Nuclear Medicine, Dept of Health Sciences, University of Genova, Genova, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Buschiazzo
authors.affiliation: CNR Institute of Bioimages and Molecular Physiology, Section of Genova, Genova, Italy; IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marini
authors.affiliation: Nuclear Medicine, Dept of Health Sciences, University of Genova, Genova, Italy; IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: De Flora
authors.affiliation: Department of Experimental Medicine and CEBR, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zocchi
mesh_terms: D041721:3T3-L1 Cells; D000040:Abscisic Acid / Q000494:pharmacology*; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D000040:Abscisic Acid; D005947:Glucose
keywords: BAT; Glycemic control; Insulin; LANCL2; MicroPET; WAT