ArticleProceedings of the National Academy of Sciences of the United States of America2023
Lipid kinase PIK3C3 maintains healthy brown and white adipose tissues to prevent metabolic diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
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- Characterization of Corneal Defects in ATG7-Deficient Mice.International journal of molecular sciences · 2025Article
- Serum- and glucocorticoid-induced kinase 3 orchestrates glucocorticoid signaling to facilitate chromatin remodeling during murine adipogenesis.The Journal of clinical investigation · 2025Article
- Paeoniflorin: a review of its pharmacology, pharmacokinetics and toxicity in diabetes.Frontiers in pharmacology · 2025Review
- Expression, Characteristics, and Clinical Target Prediction of PIK3C3/ vps34 in Gastric Cancer.Current cancer drug targets · 2025Article
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- Regulatory Mechanisms Governing the Autophagy-Initiating VPS34 Complex and Its inhibitors.Biomolecules & therapeutics · 2024Review
- Targeting Autophagy: A Promising Therapeutic Strategy for Diabetes Mellitus and Diabetic Nephropathy.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Review
- Taurine modulates host cell responses toInfection and immunity · 2024Article
- Futile lipid cycling: from biochemistry to physiology.Nature metabolism · 2024Review
- Loss of FoxO1 activates an alternate mechanism of mitochondrial quality control for healthy adipose browning.Clinical science (London, England : 1979) · 2024Article
- The dual role of autophagy in suppressing and promoting hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
- Unravelling the genetic basis for skeletal muscle mitochondrial DNA copy number variations in pigs.Science China. Life sciences · 2024Article
- Glycosphingolipids are linked to elevated neurotransmission and neurodegeneration in a Drosophila model of Niemann Pick type C.Disease models & mechanisms · 2023Article
- PIK3C3/VPS34 keeps body fats healthy.Autophagy · 2023Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Adequate mass and function of adipose tissues (ATs) play essential roles in preventing metabolic perturbations. The pathological reduction of ATs in lipodystrophy leads to an array of metabolic diseases. Understanding the underlying mechanisms may benefit the development of effective therapies. Several cellular processes, including autophagy and vesicle trafficking, function collectively to maintain AT homeostasis. Here, we investigated the impact of adipocyte-specific deletion of the lipid kinase phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) on AT homeostasis and systemic metabolism in mice. We report that PIK3C3 functions in all ATs and that its absence disturbs adipocyte autophagy and hinders adipocyte differentiation, survival, and function with differential effects on brown and white ATs. These abnormalities cause loss of white ATs, whitening followed by loss of brown ATs, and impaired "browning" of white ATs. Consequently, mice exhibit compromised thermogenic capacity and develop dyslipidemia, hepatic steatosis, insulin resistance, and type 2 diabetes. While these effects of PIK3C3 largely contrast previous findings with the autophagy-related (ATG) protein ATG7 in adipocytes, mice with a combined deficiency in both factors reveal a dominant role of the PIK3C3-deficient phenotype. We have also found that dietary lipid excess exacerbates AT pathologies caused by PIK3C3 deficiency. Surprisingly, glucose tolerance is spared in adipocyte-specific PIK3C3-deficient mice, a phenotype that is more evident during dietary lipid excess. These findings reveal a crucial yet complex role for PIK3C3 in ATs, with potential therapeutic implications.
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