The ABA/LANCL1/2 Hormone/Receptor System Controls Adipocyte Browning and Energy Expenditure

Author:

Spinelli Sonia1ORCID,Cossu Vanessa2,Passalacqua Mario1ORCID,Hansen Jacob B.3ORCID,Guida Lucrezia1,Magnone Mirko1,Sambuceti Gianmario24ORCID,Marini Cecilia25,Sturla Laura1ORCID,Zocchi Elena1

Affiliation:

1. Section of Biochemistry, Department of Experimental Medicine, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy

2. IRCCS Ospedale Policlinico San Martino, U.O. Medicina Nucleare, 16132 Genova, Italy

3. Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark

4. Department of Health Sciences, University of Genoa, 16132 Genova, Italy

5. Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 20054 Milan, Italy

Abstract

The abscisic acid (ABA)/LANC-like protein 1/2 (LANCL1/2) hormone/receptor system regulates glucose uptake and oxidation, mitochondrial respiration, and proton gradient dissipation in myocytes. Oral ABA increases glucose uptake and the transcription of adipocyte browning-related genes in rodent brown adipose tissue (BAT). The aim of this study was to investigate the role of the ABA/LANCL system in human white and brown adipocyte thermogenesis. Immortalized human white and brown preadipocytes, virally infected to overexpress or silence LANCL1/2, were differentiated in vitro with or without ABA, and transcriptional and metabolic targets critical for thermogenesis were explored. The overexpression of LANCL1/2 increases, and their combined silencing conversely reduces mitochondrial number, basal, and maximal respiration rates; proton gradient dissipation; and the transcription of uncoupling genes and of receptors for thyroid and adrenergic hormones, both in brown and in white adipocytes. The transcriptional enhancement of receptors for browning hormones also occurs in BAT from ABA-treated mice, lacking LANCL2 but overexpressing LANCL1. The signaling pathway downstream of the ABA/LANCL system includes AMPK, PGC-1α, Sirt1, and the transcription factor ERRα. The ABA/LANCL system controls human brown and “beige” adipocyte thermogenesis, acting upstream of a key signaling pathway regulating energy metabolism, mitochondrial function, and thermogenesis.

Funder

University of Genova, Italy

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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