Related Experiment Video

Updated: Aug 14, 2026

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

AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2alpha in adipocytes

Yossi Dagon1, Yosefa Avraham, Elliot M Berry

  • 1Department of Human Nutrition and Metabolism, Braun School of Public Health, Faculty of Medicine, Hebrew University, Hadassah Medical School, Israel.

Biochemical and Biophysical Research Communications
|December 27, 2005
PubMed

Insights

AMP-activated protein kinase (AMPK) activation reduces fat cells by triggering apoptosis and inhibiting adipogenic genes. This effect is mediated by eukaryotic initiation factor-2 alpha (eIF2alpha) phosphorylation, suggesting a new target for diminishing adiposity.

Area of Science:

  • Metabolic regulation
  • Cellular biology
  • Adipogenesis

Background:

  • AMP-activated protein kinase (AMPK) is a key regulator of glucose and lipid metabolism.
  • AMPK's role in controlling adipose tissue content is debated.
  • F442a adipocytes were used to investigate AMPK's effects.

Purpose of the Study:

  • To examine the impact of the AMPK activator AICAR on adipocytes.
  • To elucidate the molecular mechanisms by which AMPK influences adiposity.

Main Methods:

  • Treatment of F442a adipocytes with AICAR.
  • Assessing apoptosis, lipolysis, and adipogenic gene expression (PPARgamma, C/EBPalpha).
  • Investigating the role of eukaryotic initiation factor-2 alpha (eIF2alpha) phosphorylation and its inhibition by 2-Aminopurine (2-AP).

Main Results:

  • AICAR induced dose-dependent apoptosis and inhibited lipolysis.
  • AICAR downregulated key adipogenic genes PPARgamma and C/EBPalpha.
  • AICAR treatment led to eIF2alpha phosphorylation, which was reversed by 2-AP, restoring gene expression and lipolysis.

Conclusions:

  • AMPK activation promotes adipocyte death and reduces fat cell differentiation.
  • eIF2alpha phosphorylation is a crucial mediator of AMPK's anti-adipogenic effects.
  • Targeting the eIF2alpha pathway may offer a strategy to reduce adiposity by controlling fat cell number.

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

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function09:20

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function

Published on: May 4, 2021

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,...
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 rapamycin-insensitive companion...
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...
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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...