ArticleMolecular endocrinology (Baltimore, Md.)2012
Melanocortin-induced PKA activation inhibits AMPK activity via ERK-1/2 and LKB-1 in hypothalamic GT1-7 cells.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- Melanocortin-4 Receptor Antagonism Inhibits Colorectal and Anaplastic Thyroid Cancer In Vitro and In Vivo.Journal of clinical medicine · 2025Article
- Aspects of β-sitosterol's Pharmacology, Nutrition and Analysis.Current pharmaceutical biotechnology · 2025Review
- MC4R Variants Modulate α-MSH and Setmelanotide Induced Cellular Signaling at Multiple Levels.The Journal of clinical endocrinology and metabolism · 2024Article
- Recent Research on Mechanisms of Feeding Regulation in Chicks.The journal of poultry science · 2024Review
- Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance.Metabolites · 2023Review
- The role of liver kinase B1 in tumor progression through regulation of lipid metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Article
- Biased signaling in naturally occurring mutations of G protein-coupled receptors associated with diverse human diseases.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Alanine Scanning Mutagenesis of the DRYxxI Motif and Intracellular Loop 2 of Human Melanocortin-4 Receptor.International journal of molecular sciences · 2020Article
- Regulation of AMPK activity by type 10 adenylyl cyclase: contribution to the mitochondrial biology, cellular redox and energy homeostasis.Cellular and molecular life sciences : CMLS · 2019Article
- Aerobic Exercise Training Decreases Hepatic Asprosin in Diabetic Rats.Journal of clinical medicine · 2019Article
- Aquaporin-3 deficiency slows cyst enlargement in experimental mouse models of autosomal dominant polycystic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Metabolism and mitochondria in polycystic kidney disease research and therapy.Nature reviews. Nephrology · 2018Review
- Melanocortin Receptor-4 and Glioblastoma Cells: Effects of the Selective Antagonist ML00253764 Alone and in Combination with Temozolomide In Vitro and In Vivo.Molecular neurobiology · 2018Article
- Procyanidin B2 3,3″-di-O-gallate induces oxidative stress-mediated cell death in prostate cancer cells via inhibiting MAP kinase phosphatase activity and activating ERK1/2 and AMPK.Molecular carcinogenesis · 2018Article
- Biased signaling at neural melanocortin receptors in regulation of energy homeostasis.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Activation of Transient Receptor Potential Vanilloid 4 Impairs the Dendritic Arborization of Newborn Neurons in the Hippocampal Dentate Gyrus through the AMPK and Akt Signaling Pathways.Frontiers in molecular neuroscience · 2017Article
- Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance.Molecular metabolism · 2015Article
- Transcriptional upregulation of microtubule-associated protein 2 is involved in the protein kinase A-induced decrease in the invasiveness of glioma cells.Neuro-oncology · 2015Article
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4 authors at 1 institution in 1 country.
Funding
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Abstract
α-Melanocyte-stimulating hormone (α-MSH)-induced activation of the melanocortin-4 receptor in hypothalamic neurons increases energy expenditure and inhibits food intake. Active hypothalamic AMP-activated protein kinase (AMPK) has recently been reported to enhance food intake, and in vivo experiments suggested that intrahypothalamic injection of melanocortins decreased food intake due to the inhibition of AMPK activity. However, it is not clear whether α-MSH affects AMPK via direct intracellular signaling cascades or if the release of paracrine factors is involved. Here, we used a murine, hypothalamic cell line (GT1-7 cells) and monitored AMPK phosphorylation at Thr(172), which has been suggested to increase AMPK activity. We found that α-MSH dephosphorylated AMPK at Thr(172) and consequently decreased phosphorylation of the established AMPK substrate acetyl-coenzyme A-carboxylase at Ser(79). Inhibitory effects of α-MSH on AMPK were blocked by specific inhibitors of protein kinase A (PKA) or ERK-1/2, pointing to an important role of both kinases in this process. Because α-MSH-induced activation of ERK-1/2 was blunted by PKA inhibitors, we propose that ERK-1/2 serves as a link between PKA and AMPK in GT1-7 cells. Furthermore, down-regulation of liver kinase B-1, but not inhibition of calcium-calmodulin-dependent kinase kinase-β or TGFβ-activated kinase-1 decreased basal phosphorylation of AMPK and its dephosphorylation induced by α-MSH. Thus, we propose that α-MSH inhibits AMPK activity via a linear pathway, including PKA, ERK-1/2, and liver kinase B-1 in GT1-7 cells. Given the importance of the melanocortin system in the formation of adipositas, detailed knowledge about this pathway might help to develop drugs targeting obesity.
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