Related Experiment Video

Updated: Sep 11, 2025

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

3.0K

MRP4 deficiency drives lipid metabolism dysregulation and adipose tissue inflammation through cAMP-CREB-CRTC2

Ankit P Laddha1, Hangyu Wu1, Jaeeun Lee2

  • 1Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.

Life Sciences
|August 15, 2025
PubMed

Insights

Multidrug resistance-associated protein 4 (MRP4) deficiency exacerbates obesity and metabolic dysfunction by promoting adipose tissue inflammation and fibrosis. This occurs through the activation of the cAMP-CREB-CRTC2 signaling pathway, highlighting MRP4's role in metabolic health.

Area of Science:

  • Biochemistry and Molecular Biology
  • Metabolic Research
  • Physiology

Background:

  • Multidrug resistance-associated protein 4 (MRP4/ABCC4) is a plasma membrane transporter crucial for metabolite and xenobiotic efflux.
  • Previous studies suggest MRP4 involvement in adipogenesis and fatty acid metabolism.
  • MRP4 deficiency in mice is linked to obesity and diabetes, but mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of MRP4 in adipose tissue dysfunction.
  • To understand MRP4's impact on metabolic regulation under high-fat, high-sucrose (HFHS) diet conditions.

Main Methods:

  • MRP4 knockout (MRP4-/-) and wild-type (WT) mice were fed chow or HFHS diets for 24 weeks.
  • Assessed body weight, plasma glucose, cholesterol, insulin, glucose tolerance, and insulin sensitivity.
  • Analyzed epididymal adipose tissue for gene/protein expression, histology, and cAMP levels.

Main Results:

  • MRP4-/- mice exhibited increased body weight gain, adiposity, and adipocyte hypertrophy, with exacerbated metabolic dysfunction on HFHS diet.
  • These mice showed impaired glucose/insulin metabolism, reduced physical activity, and altered energy expenditure.
  • Upregulation of adipogenic, fibrotic, and inflammatory genes, alongside elevated cAMP, P-CREB, and CRTC2, indicated activated signaling pathways.

Conclusions:

  • MRP4 deficiency promotes adipose tissue inflammation, fibrosis, and metabolic dysfunction.
  • Activation of the cAMP-CREB-CRTC2 signaling axis is a key mechanism.
  • MRP4 plays a novel role in maintaining adipose tissue homeostasis and preventing diet-induced metabolic disease.
Keywords:
AdiposityFibrosisGlucose toleranceMRP4cAMP

More Related Videos

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

15.3K
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

6.8K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.0K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.0K
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
31
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K