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

• 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Adipocytes

White

Adipose Tissue

Humans

Lipids

Pyruvate Carboxylase

RNA

Long Noncoding

angiotensin 2 receptor antagonist

beta adrenergic receptor blocking agent

calcium channel blocking agent

dipeptidyl carboxypeptidase inhibitor

hydroxymethylglutaryl coenzyme A reductase inhibitor

long untranslated RNA

metformin

thiazide diuretic agent

lipid

enzyme activity

metabolism

mitochondrion

RNA

adipocyte

Article

clinical article

cohort analysis

controlled study

electron microscopy

energy metabolism

female

gene expression

human

human cell

hypertension

insulin resistance

lipid degradation

lipid metabolism

lipogenesis

metabolic phenotype

non insulin dependent diabetes mellitus

obesity

phase separation

protein analysis

protein expression

white adipocyte

white adipose tissue

genetics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)