ArticleNature communications2021
Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Exercise-regulated lipolysis: Its role and mechanism in health and diseases.Journal of advanced research · 2025Review
- Insulin resistance in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genome-Wide Association Studies of Body Weight and Average Daily Gain in Chinese Dongliao Black Pigs.International journal of molecular sciences · 2025Article
- Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis.Nature communications · 2025Article
- Gallic acid prevents obesity in mice on a high-fat diet via the gut microbiota-adipose tissue axis.Current research in food science · 2025Article
- Genomic-Inbreeding Landscape and Selection Signatures in the Polo Argentino Horse Breed.International journal of molecular sciences · 2024Article
- Two-Pronged Attack: Dual Activation of Fat Reduction Using Near-Infrared-Responsive Nanosandwich for Targeted Anti-Obesity Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cellular Senescence and Extracellular Vesicles in the Pathogenesis and Treatment of Obesity-A Narrative Review.International journal of molecular sciences · 2024Review
- New advances of adiponectin in regulating obesity and related metabolic syndromes.Journal of pharmaceutical analysis · 2024Review
- Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.Current drug targets · 2024Review
- Tangzhiping Decoction Improves Glucose and Lipid Metabolism and Exerts Protective Effects Against White Adipose Tissue Dysfunction in Prediabetic Mice.Drug design, development and therapy · 2024Article
- Loss of pleckstrin homology domain and leucine-rich repeat protein phosphatase 2 has protective effects on high glucose-injured retinal ganglion cells via the effect on the Akt-GSK-3β-Nrf2 pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism.International journal of molecular sciences · 2023Review
- Macrophage metabolism in nonalcoholic fatty liver disease.Frontiers in immunology · 2023Review
- PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.Cell communication and signaling : CCS · 2022Article
- Cdo1 promotes PPARγ-mediated adipose tissue lipolysis in male mice.Nature metabolism · 2022Article
- Approaches to Measuring the Activity of Major Lipolytic and Lipogenic Enzymes In Vitro and Ex Vivo.International journal of molecular sciences · 2022Review
- Correlations Between Endocrine Hormones and Cognitive Function in Patients with Obesity: a Cross-sectional Study.Obesity surgery · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Increased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.
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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.