ArticleMolecular metabolism2018
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Exercise and smoking: health rivals revealing shared protective mechanisms in Parkinson's?NPJ Parkinson's disease · 2026Review
- Propionate Induces Energy Expenditure via Browning in Mesenteric Adipose Tissue.The Journal of clinical endocrinology and metabolism · 2025Article
- Harnessing mitochondrial biogenesis to combat acute kidney injury: Current insights and futuredirections.Genes & diseases · 2025Review
- Nutritional Influences on Brown and Beige Adipocyte: Unraveling the Molecular Mechanisms and Metabolic Implications.Food science & nutrition · 2025Review
- Naa10p impairs PGC-1α/Pparγ2 interaction to inhibit mitochondrial protection in pancreatitis.Journal of cell communication and signaling · 2025Article
- Exploring Genetic Markers for Cold-Heat Patterns: Integrating Traditional Medicine With Modern Genomic Research.Genetics research · 2025Article
- β3-Adrenergic receptor overexpression in cardiomyocytes preconditions mitochondria to withstand ischemia-reperfusion injury.Basic research in cardiology · 2024Article
- Marine fungusFrontiers in pharmacology · 2024Article
- Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia.Extracellular vesicles and circulating nucleic acids · 2024Review
- Dietary kaempferol exerts anti-obesity effects by inducing the browing of white adipocytes via the AMPK/SIRT1/PGC-1α signaling pathway.Current research in food science · 2024Article
- The potential mechanism of gut microbiota-microbial metabolites-mitochondrial axis in progression of diabetic kidney disease.Molecular medicine (Cambridge, Mass.) · 2023Review
- Human Umbilical Vein Endothelial Cells Survive on the Ischemic TCA Cycle under Lethal Ischemic Conditions.Journal of proteome research · 2022Article
- Critical Sites on Ostreolysin Are Responsible for Interaction with Cytoskeletal Proteins.Biomedicines · 2022Article
- Induction of beige-like adipocyte markers and functions in 3T3-L1 cells by Clk1 and PKCβII inhibitory molecules.Journal of cellular and molecular medicine · 2022Article
- Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS.Biomolecules · 2022Article
- Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders.Frontiers in immunology · 2022Review
- Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes.Life (Basel, Switzerland) · 2021Article
- Review
- Concentrated extract of Prunus mume fruit exerts dual effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing beiging/browning.Food & nutrition research · 2021Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1α1 is a transcriptional coactivator with no known ligand-binding properties. While, PGC-1α1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions.
methodsWe designed a cell-based high-throughput screening system to identify PGC-1α1 protein stabilizers. Positive hits were tested for their ability to induce endogenous PGC-1α1 protein accumulation and activate target gene expression in brown adipocytes. Select compounds were analyzed for their effects on global gene expression and cellular respiration in adipocytes.
resultsAmong 7,040 compounds screened, we highlight four small molecules with high activity as measured by: PGC-1α1 protein accumulation, target gene expression, and uncoupled mitochondrial respiration in brown adipocytes.
conclusionsWe identify compounds that induce PGC-1α1 protein accumulation and show that this increases uncoupled respiration in brown adipocytes. This screening platform establishes the foundation for a new class of therapeutics with potential use in obesity and associated disorders.
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Registered trials
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