The antiadipogenic effect of the pentacyclic triterpenoid isoarborinol is mediated by LKB1-AMPK activation

Yesenia Arcos-Reyes1, Gildardo Rivera2, Laurence A Marchat1

  • 1Instituto Politécnico Nacional, Escuela Nacional de Medicina y Homeopatía, Laboratorio de Biomedicina Molecular 2, México City, México.

Plos One
|September 3, 2025
PubMed

Insights

Isoarborinol, a plant-derived compound, effectively inhibits fat cell (adipocyte) differentiation and reduces lipid accumulation. This anti-obesity effect is linked to activating the LKB1-AMPK pathway, offering potential therapeutic strategies for metabolic disorders.

Area of Science:

  • Metabolomics
  • Molecular Biology
  • Pharmacology

Background:

  • Obesity is a global health crisis linked to chronic diseases.
  • Plant metabolites, like pentacyclic triterpenes, show promise for anti-obesity therapies.
  • These compounds can modulate adipogenesis regulators and signaling pathways, including LKB1-AMPK.

Purpose of the Study:

  • To investigate the anti-adipogenic effects of the pentacyclic triterpene isoarborinol.
  • To elucidate the molecular mechanisms underlying isoarborinol's action on adipogenesis in 3T3-L1 cells.

Main Methods:

  • Cell culture of 3T3-L1 pre-adipocytes.
  • Assessment of adipogenic differentiation and lipid accumulation.
  • Analysis of gene and protein expression related to adipogenesis and lipogenesis.
  • Western blot analysis for LKB1 and AMPK phosphorylation.

Main Results:

  • Isoarborinol inhibited 3T3-L1 cell differentiation and lipid accumulation in a dose-dependent manner.
  • The molecule altered the expression of key adipogenic regulators: C/EBPβ, C/EBPδ, C/EBPα, PPARγ, and SREBP-1C.
  • Isoarborinol increased LKB1 and AMPK phosphorylation, downregulating lipogenic factors ACC1, FAS, and FABP4.

Conclusions:

  • Isoarborinol exhibits significant anti-adipogenic properties.
  • Its mechanism involves LKB1-AMPK pathway activation, impacting adipogenesis master regulators and lipogenic factors.
  • Isoarborinol represents a potential therapeutic candidate for managing obesity.

Related Concept Videos

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
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...
3.9K
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
2.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.9K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K