ArticleThe Journal of biological chemistry2012
Lipolytic products activate peroxisome proliferator-activated receptor (PPAR) α and δ in brown adipocytes to match fatty acid oxidation with supply.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 193 citations in OpenAlex.
- Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.PLoS biology · 2013Trial
- Differences of PPARD Expression in the Liver of Cattle with Different Marbling Grades.Animals : an open access journal from MDPI · 2026Article
- Single-nucleus mRNA-sequencing reveals dynamics of lipogenic and thermogenic adipocyte populations in murine brown adipose tissue in response to cold exposure.Molecular metabolism · 2025Article
- Epac1 mediates thermogenesis and lipolysis in white adipose tissue via the p38γ-NFAT5 axis in a PKA-independent manner.Clinical science (London, England : 1979) · 2025Article
- Plin5: A potential therapeutic target for type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- Thermogenesis and Energy Metabolism in Brown Adipose Tissue in Animals Experiencing Cold Stress.International journal of molecular sciences · 2025Review
- Metabolic-Associated Steatotic Liver Disease: From Molecular Mechanisms to Novel Therapies.International journal of hepatology · 2025Review
- Exposure to PCB52 (2,2',5,5'-tetrachlorobiphenyl) blunts induction of the gene for uncoupling protein 1 (UCP1) in white adipose.Environmental toxicology and pharmacology · 2025Article
- Chronic β3-AR stimulation activates distinct thermogenic mechanisms in brown and white adipose tissue and improves systemic metabolism in aged mice.Aging cell · 2024Article
- Direct effects of adipocyte lipolysis on AMPK through intracellular long-chain acyl-CoA signaling.Scientific reports · 2024Article
- Adipose retinol saturase is regulated by β-adrenergic signaling and its deletion impairs lipolysis in adipocytes and acute cold tolerance in mice.Molecular metabolism · 2024Article
- p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL.Nature metabolism · 2024Article
- Brown adipocyte and browning thermogenesis: metabolic crosstalk beyond mitochondrial limits and physiological impacts.Adipocyte · 2023Review
- Aurantio-obtusin ameliorates obesity by activating PPARα-dependent mitochondrial thermogenesis in brown adipose tissues.Acta pharmacologica Sinica · 2023Article
- Synergistic Effects of Heat-Treated Green Tea Extract and Enzymatically-Modified Isoquercitrin in Preventing Obesity.Nutrients · 2023Article
- A FRET sensor for the real-time detection of long chain acyl-CoAs and synthetic ABHD5 ligands.Cell reports methods · 2023Article
- PERM1 regulates genes involved in fatty acid metabolism in the heart by interacting with PPARα and PGC-1α.Scientific reports · 2022Article
- Drug-Initiated Activity Metabolomics Identifies Myristoylglycine as a Potent Endogenous Metabolite for Human Brown Fat Differentiation.Metabolites · 2022Article
- Cold exposure induces lipid dynamics and thermogenesis in brown adipose tissue of goats.BMC genomics · 2022Article
- Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism.Nature communications · 2022Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
β-Adrenergic receptors (β-ARs) promote brown adipose tissue (BAT) thermogenesis by mobilizing fatty acids and inducing the expression of oxidative genes. β-AR activation increases the expression of oxidative genes by elevating cAMP, but whether lipolytic products can modulate gene expression is not known. This study examined the role that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) plays in the induction of gene expression. Activation of brown adipocytes by β-AR agonism or 8-bromo-cyclic AMP increased the expression of PGC1α, PDK4, PPARα, uncoupling protein 1 (UCP1), and neuron-derived orphan receptor-1 (NOR-1), and concurrent inhibition of HSL reduced the induction of PGC1α, PDK4, PPARα, and UCP1 but not NOR-1. Similar results were observed in the BAT of mice following pharmacological or genetic inhibition of HSL and in brown adipocytes with stable knockdown of ATGL. Conversely, treatments that increase endogenous fatty acids elevated the expression of oxidative genes. Pharmacological antagonism and siRNA knockdown indicate that PPARα and PPARδ modulate the induction of oxidative genes by β-AR agonism. Using a live cell fluorescent reporter assay of PPAR activation, we demonstrated that ligands for PPARα and -δ, but not PPARγ, were rapidly generated at the lipid droplet surface and could transcriptionally activate PPARα and -δ. Knockdown of ATGL reduced cAMP-mediated induction of genes involved in fatty acid oxidation and oxidative phosphorylation. Consequently, ATGL knockdown reduced maximal oxidation of fatty acids, but not pyruvate, in response to cAMP stimulation. Overall, the results indicate that lipolytic products can activate PPARα and PPARδ in brown adipocytes, thereby expanding the oxidative capacity to match enhanced fatty acid supply.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.