The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase

Alastair G. Kerr, Zuoneng Wang, Na Wang, Kelvin H. M. Kwok, Jutta Jalkanen, Alison Ludzki, Simon Lecoutre, Dominique Langin, Martin O. Bergo, Ingrid Dahlman, Carsten Mim, Peter Arner () and Hui Gao ()
Additional contact information
Alastair G. Kerr: Karolinska Institutet, Karolinska University Hospital Huddinge
Zuoneng Wang: Royal Technical Institute
Na Wang: Karolinska Institutet, Karolinska University Hospital Huddinge
Kelvin H. M. Kwok: Karolinska Institutet, Karolinska University Hospital Huddinge
Jutta Jalkanen: Karolinska Institutet, Karolinska University Hospital Huddinge
Alison Ludzki: Karolinska Institutet, Karolinska University Hospital Huddinge
Simon Lecoutre: Karolinska Institutet, Karolinska University Hospital Huddinge
Dominique Langin: Institute of Metabolic and Cardiovascular Diseases (I2MC), Institut National de la Santé et de la Recherche Médicale (Inserm), Université de Toulouse, UPS
Martin O. Bergo: Karolinska Institutet
Ingrid Dahlman: Karolinska Institutet, Karolinska University Hospital Huddinge
Carsten Mim: Royal Technical Institute
Peter Arner: Karolinska Institutet, Karolinska University Hospital Huddinge
Hui Gao: Karolinska Institutet

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract The pleiotropic function of long noncoding RNAs is well recognized, but their direct role in governing metabolic homeostasis is less understood. Here, we describe a human adipocyte-specific lncRNA, ADIPINT, that regulates pyruvate carboxylase, a pivotal enzyme in energy metabolism. We developed an approach, Targeted RNA-protein identification using Orthogonal Organic Phase Separation, which identifies that ADIPINT binds to pyruvate carboxylase and validated the interaction with electron microscopy. ADIPINT knockdown alters the interactome and decreases the abundance and enzymatic activity of pyruvate carboxylase in the mitochondria. Reduced ADIPINT or pyruvate carboxylase expression lowers adipocyte lipid synthesis, breakdown, and lipid content. In human white adipose tissue, ADIPINT expression is increased in obesity and linked to fat cell size, adipose insulin resistance, and pyruvate carboxylase activity. Thus, we identify ADIPINT as a regulator of lipid metabolism in human white adipocytes, which at least in part is mediated through its interaction with pyruvate carboxylase.

Date: 2022
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DOI: 10.1038/s41467-022-30620-0

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