Related Experiment Video
Updated: Jan 18, 2026
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
19.8K
Convergent Metabolic Pathways in MASH Therapeutics: An AMPK-Centric Analysis
Seungchan Choi1, Jin-Seok Jung2, Yie-Sung Seo3,4
1Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Journal of Cellular and Molecular Medicine
|January 16, 2026
Summary
Metabolic dysfunction-associated steatohepatitis (MASH) treatments converge on AMP-activated protein kinase (AMPK) signaling. This framework aids understanding diverse MASH drug mechanisms and personalizing therapy.
Area of Science:
- Hepatology
- Metabolic Diseases
- Pharmacology
Background:
- Metabolic dysfunction-associated steatohepatitis (MASH) is a significant cause of liver disease linked to metabolic issues.
- New MASH therapies like resmetirom and GLP-1 receptor agonists offer promise, but their mechanisms require clarification.
Purpose of the Study:
- To propose a mechanistic framework for MASH therapeutics centered on AMP-activated protein kinase (AMPK) signaling.
- To synthesize evidence on how various drugs activate AMPK, directly or indirectly.
- To inform combination therapy strategies for MASH.
Main Methods:
- Review of current literature on MASH and metabolism-based therapeutics.
- Analysis of drug mechanisms, focusing on AMPK activation pathways.
- Comparison of liver-targeted versus systemic drug effects.
Main Results:
- Diverse MASH drugs, including pioglitazone, GLP-1 RAs, SGLT2 inhibitors, resmetirom, and statins, converge on AMPK signaling.
- AMPK activation occurs through systemic effects (weight loss, glycemic control) or direct hepatocyte actions.
- Resmetirom's direct liver action contrasts with semaglutide's systemic effects.
Conclusions:
- An AMPK-centric framework clarifies MASH drug pharmacology.
- Understanding AMPK signaling facilitates personalized MASH treatment strategies.
- This approach supports rational combination therapy development for MASH.
Keywords:
AMP‐activated protein kinaseGLP‐1 receptor agonistMASHMASLDSGLT2 inhibitorresmetiromstatinsMore Related Videos
Related Concept Videos
01:19Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
01:22PI3K/mTOR/AKT Signaling Pathway
5.4K
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...
5.4K
03:03mTOR Signaling and Cancer Progression
4.6K
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 mTOR pathway or the...
4.6K
01:07MAPK Signaling Cascades
7.9K
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...
7.9K
01:22Amplifying Signals via Enzymatic Cascade
17.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
17.5K
01:25cAMP-dependent Protein Kinase Pathways
8.3K
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,...
8.3K