| 1. |
- Alastair, Kerr, et al.
(författare)
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The long noncoding RNA ADIPINT is a gatekeeper of pyruvate carboxylasefunction regulating human fat cell metabolism
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The pleiotropic function of long noncoding RNAs (lncRNAs) is well recognized,but their direct role in governingmetabolic homeostasis is less understood. Herein,we describe a human adipocyte-specific lncRNA, ADIPINT, that regulatespyruvate carboxylase (PC) an enzyme pivotal to energy metabolism. With a novelapproach, Targeted RNA-protein identification using Orthogonal Organic PhaseSeparation (TROOPS) and validation with electron microscopy, we show thatADIPINT binds to PC. ADIPINT knockdown alters the interactome anddecreases the mitochondrial abundance and enzymatic activty of PC. Decreases inADIPINT or PC expression reduce adipocyte lipid synthesis, breakdown and lipidcontent. In human white adipose tissue, ADIPINT expression is increased inobesity, linked to fat cell size, adipose insulin resistance and PC activity. Thus, weidentify ADIPINT as a regulator of lipid metabolism in human white adipocytes,which at least in part is mediated through its interaction with PC.
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| 2. |
- Kerr, Alastair, et al.
(författare)
-
The long noncoding RNA ADIPINT is a gatekeeper of pyruvate carboxylase function regulating human fat cell metabolism
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The pleiotropic function of long noncoding RNAs (lncRNAs) is well recognized, but their direct role in governing metabolic homeostasis is less understood. Herein, we describe a human adipocyte-specific lncRNA, ADIPINT, that regulates pyruvate carboxylase (PC) an enzyme pivotal to energy metabolism. With a novel approach, Targeted RNA-protein identification using Orthogonal Organic Phase Separation (TROOPS) and validation with electron microscopy, we show that ADIPINT binds to PC. ADIPINT knockdown alters the interactome and decreases the mitochondrial abundance and enzymatic activty of PC. Decreases in ADIPINT or PC expression reduce adipocyte lipid synthesis, breakdown and lipid content. In human white adipose tissue, ADIPINT expression is increased in obesity, linked to fat cell size, adipose insulin resistance and PC 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 PC.
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