ArticleMolecular metabolism2015
E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Adenovirus 36 prevalence and association with human obesity: a systematic review.International journal of obesity (2005) · 2021Pooled it
- Pre-clinical studies show anti-diabetic effect of INSPARIN, a protein derived from the E4orf1 gene of a human adenovirus.Nutrition & diabetes · 2025Article
- E4orf1 improves adipose tissue-specific metabolic risk factors and indicators of cognition function in a mouse model of Alzheimer's disease.Nutrition & diabetes · 2023Article
- E4orf1 Prevents Progression of Fatty Liver Disease in Mice on High Fat Diet.International journal of molecular sciences · 2022Article
- E4orf1-induced reduction in endogenous insulin level is independent of pancreas endocrine function.International journal of obesity (2005) · 2022Article
- Adipocyte commitment of 3T3-L1 cells is required to support human adenovirus 36 productive replication concurrent with altered lipid and glucose metabolism.Frontiers in cellular and infection microbiology · 2022Article
- Antidiabetic E4orf1 protein prevents hepatic steatosis and reduces markers of aging-related cellular damage in high fat fed older mice.BMJ open diabetes research & care · 2021Article
- Article
- Nanoparticle-mediated in vitro delivery of E4orf1 to preadipocytes is a clinically relevant delivery system to improve glucose uptake.International journal of obesity (2005) · 2020Article
- What we know and what we need to know about adenovirus 36-induced obesity.International journal of obesity (2005) · 2020Review
- A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive β-Cell Hyperplasia.Diabetes · 2020Article
- E4orf1 protein reduces the need for endogenous insulin.Nutrition & diabetes · 2019Article
- E4orf1: A protein for enhancing glucose uptake despite impaired proximal insulin signaling.PloS one · 2018Article
- Insulin-sparing and fungible effects of E4orf1 combined with an adipocyte-targeting sequence in mouse models of type 1 and type 2 diabetes.International journal of obesity (2005) · 2017Article
- Hepatic Expression of Adenovirus 36 E4ORF1 Improves Glycemic Control and Promotes Glucose Metabolism Through AKT Activation.Diabetes · 2017Article
- Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes.Cell reports · 2016Article
- An adenovirus-derived protein: A novel candidate for anti-diabetic drug development.Biochimie · 2016Article
- Adipocyte-specific blockade of gamma-secretase, but not inhibition of Notch activity, reduces adipose insulin sensitivity.Molecular metabolism · 2016Article
- Article
- Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.AdipocyteReview
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
background/purposeType 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism.
methodsWe have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes.
resultsUsing the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions. The mice further exhibit reduced circulating adiponectin levels that ultimately lead to impaired lipid clearance, and inflamed and fibrotic white adipose tissues. Nevertheless, they are protected from diet-induced hepatic steatosis. As we observe constitutively elevated p-Akt levels in the adipocytes, even under conditions of low insulin levels, this pinpoints enhanced Ras-ERK-MAPK signaling in transgenic adipocytes as a potential alternative route to bypass proximal insulin signaling events.
conclusionWe conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte.
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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.