ArticleMolecular metabolism2019
Brown fat organogenesis and maintenance requires AKT1 and AKT2.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Regulatory modules of human thermogenic adipocytes: functional genomics of large cohort and Meta-analysis derived marker-genes.BMC genomics · 2021Pooled it
- Four pleiotropic loci associated with fat mass and lean mass.International journal of obesity (2005) · 2020Pooled it
- Inter-tissue relationships of gene expression in liver, muscle and adipose tissue of children with end-stage chronic liver disease.Journal of pediatric gastroenterology and nutrition · 2026Article
- Biomarkers of Adipose Color: A Multi-Omics Analysis Unravels the Molecular Landscape of White and Yellow Fat in Kazakh Horse.Biology · 2026Article
- The widely used Ucp1-Cre transgene elicits complex developmental and metabolic phenotypes.Nature communications · 2025Article
- Siglec-E augments adipose tissue inflammation by modulating TRAF3 signaling and monocytic myeloid-derived suppressor cells during obesity.Frontiers in immunology · 2025Article
- An efficient AAV vector system of Rec2 serotype for intravenous injection to study metabolism in brown adipocytes in vivo.Molecular metabolism · 2024Article
- Article
- Dexamethasone improves thymoma-associated myasthenia gravis via the AKT-mTOR pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Generation of a medicine food homology formula and its likely mechanism in treatment of microvascular angina.Frontiers in pharmacology · 2024Article
- The widely usedbioRxiv : the preprint server for biology · 2023Article
- Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse.Science advances · 2023Article
- In vivo study revealed pro-tumorigenic effect of CMTM3 in hepatocellular carcinoma involving the regulation of peroxisome proliferator-activated receptor gamma (PPARγ).Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy.Nature communications · 2022Article
- Uncovering the enigmatic evolution of bears in greater depth: The hybrid origin of the Asiatic black bear.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genome-Wide Analysis of microRNAs Identifies the Lipid Metabolism Pathway to Be a Defining Factor in Adipose Tissue From Different Sheep.Frontiers in veterinary science · 2022Article
- Therapeutic Target Analysis and Molecular Mechanism of Melatonin - Treated Leptin Resistance Induced Obesity: A Systematic Study of Network Pharmacology.Frontiers in endocrinology · 2022Article
- Study on the Potential Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Proteomic analysis of a murine model of lung hypoplasia induced by oligohydramnios.Pediatric pulmonology · 2021Article
- Leptin Modulates the Response of Brown Adipose Tissue to Negative Energy Balance: Implication of the GH/IGF-I Axis.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveUnderstanding the signaling mechanisms that control brown adipose tissue (BAT) development is relevant to understanding energy homeostasis and obesity. The AKT kinases are insulin effectors with critical in vivo functions in adipocytes; however, their role in adipocyte development remains poorly understood. The goal of this study was to investigate AKT function in BAT development.
methodsWe conditionally deleted Akt1 and Akt2 either individually or together with Myf5-Cre, which targets early mesenchymal precursors that give rise to brown adipocytes. Because Myf5-Cre also targets skeletal muscle and some white adipocyte lineages, comparisons were made between AKT function in BAT versus white adipose tissue (WAT) and muscle development. We also deleted both Akt1 and Akt2 in mature brown adipocytes with Ucp1-Cre or Ucp1-CreER to investigate AKT1/2 signaling in BAT maintenance.
resultsAKT1 and AKT2 are individually dispensable in Myf5-Cre lineages in vivo for establishing brown and white adipocyte precursor cell pools and for their ability to differentiate (i.e. induce PPARγ). AKT1 and AKT2 are also dispensable for skeletal muscle development, and AKT3 does not compensate in either the adipocyte or muscle lineages. In contrast, AKT2 is required for adipocyte lipid filling and efficient downstream AKT substrate phosphorylation. Mice in which both Akt1 and Akt2 are deleted with Myf5-Cre lack BAT but have normal muscle mass, and doubly deleting Akt1 and Akt2 in mature brown adipocytes, either congenitally (with Ucp1-Cre), or inducibly in older mice (with Ucp1-CreER), also ablates BAT. Mechanistically, AKT signaling promotes adipogenesis in part by stimulating ChREBP activity.
conclusionsAKT signaling is required in vivo for BAT development but dispensable for skeletal muscle development. AKT1 and AKT2 have both overlapping and distinct functions in BAT development with AKT2 being the most critical individual isoform. AKT1 and AKT2 also have distinct and complementary functions in BAT maintenance.
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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.