ArticleThe Journal of experimental medicine2021
Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 69 citations in OpenAlex.
- The role of mesencephalic astrocyte-derived neurotrophic factor in digestive diseases.Annals of medicine · 2026Review
- Dieckol suppresses lipid accumulation and promotes thermogenic markers in 3T3-L1 adipocytes via ERK/p38 MAPK signaling.Journal of physiology and biochemistry · 2026Article
- Cell-type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling.Cell reports · 2026Article
- Hepatokine ORM2 suppresses pathological ferritinophagy to prevent acute tissue injury.Cell death & disease · 2026Article
- Adipose TGR5 Deletion Promotes Hepatic Steatosis Through Decreasing Adiponectin Secretion in Mice.Diabetes · 2026Article
- Cell type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling.bioRxiv : the preprint server for biology · 2026Article
- Neuroplastin-55 is a receptor of Manf and protects against diet-induced obesity by promoting adipose browning.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- MANF improves cognitive function and attenuates neuroinflammation in APP/PS1 transgenic mice through the TLR4/MYD88/NF-κB signaling pathway.Journal of anesthesia and translational medicine · 2025Article
- Hepatic ENTPD5 Is Critical for Maintaining Metabolic Homeostasis and Promoting Brown Adipose Tissue Thermogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification and validation of the pivotal role of MANF gene in pancreatic β-cell aging using bioinformatics.Biochemistry and biophysics reports · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Myeloid-derived MANF ameliorates ethanol-induced liver injury by enhancing microRNA-223 expression.Journal of gastroenterology · 2025Article
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- Paternal Obesity-Induced H3K27me3 Elevation Leads to MANF-Mediated Transgenerational Metabolic Dysfunction in Female Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Brain-acting hepatokines: its impact on energy balance and metabolism.Frontiers in neuroscience · 2025Review
- CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The signaling pathways in obesity-related complications.Journal of cell communication and signaling · 2024Review
- Article
- Liver ACSM3 deficiency mediates metabolic syndrome via a lauric acid-HNF4α-p38 MAPK axis.The EMBO journal · 2024Article
- Friend or foe for obesity: How hepatokines remodel adipose tissues and translational perspective.Genes & diseases · 2023Review
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). Manf overexpression in liver was also associated with decreased adipose inflammation and improved insulin sensitivity and hepatic steatosis. Mechanistically, Manf could directly promote browning of white adipocytes via the p38 MAPK pathway. Blockade of p38 MAPK abolished Manf-induced browning. Consistently, liver-specific Manf knockout mice showed impaired iWAT browning and exacerbated diet-induced obesity, insulin resistance, and hepatic steatosis. Recombinant Manf reduced obesity and improved insulin resistance in both diet-induced and genetic obese mouse models. Finally, we showed that circulating Manf level was positively correlated with BMI in humans. This study reveals the crucial role of Manf in regulating thermogenesis in adipose tissue, representing a potential therapeutic target for obesity and related metabolic disorders.
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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.