ArticleEndocrinology2015
Absence of intracellular ion channels TPC1 and TPC2 leads to mature-onset obesity in male mice, due to impaired lipid availability for thermogenesis in brown adipose tissue.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Cross-Study Meta-Analysis of Blood Transcriptomes in Type 2 Diabetes.International journal of molecular sciences · 2025Pooled it
- The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology.International journal of molecular sciences · 2025Review
- Loss of endothelial TRPC1 aggravates metabolic dysfunction in obesity via disrupting adipose tissue homeostasis.Frontiers in molecular biosciences · 2025Article
- NAADP-Dependent TPC Current.Handbook of experimental pharmacology · 2023Article
- Expanding the Toolbox: Novel Modulators of Endolysosomal Cation Channels.Handbook of experimental pharmacology · 2023Article
- Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect.PLoS genetics · 2021Article
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- A screening campaign in sea urchin egg homogenate as a platform for discovering modulators of NAADP-dependent CaCell calcium · 2018Article
- Two-pore channels and disease.Biochimica et biophysica acta. Molecular cell research · 2018Review
- Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain.Physiological genomics · 2018Article
- Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions.Channels (Austin, Tex.) · 2017Review
- Metabolic alterations derived from absence of Two-Pore Channel 1 at cardiac level.Journal of biosciences · 2016Article
- Endolysosomal two-pore channels regulate autophagy in cardiomyocytes.The Journal of physiology · 2016Article
- Genetic Variants of TPCN2 Associated with Type 2 Diabetes Risk in the Chinese Population.PloS one · 2016Article
- Two-pore Channels (TPC2s) and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) at Lysosomal-Sarcoplasmic Reticular Junctions Contribute to Acute and Chronic β-Adrenoceptor Signaling in the Heart.The Journal of biological chemistry · 2015Article
- Two-Pore Channels: Lessons from Mutant Mouse Models.Messenger (Los Angeles, Calif. : Print) · 2015Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Intracellular calcium-permeable channels have been implicated in thermogenic function of murine brown and brite/beige adipocytes, respectively transient receptor potential melastin-8 and transient receptor potential vanilloid-4. Because the endo-lysosomal two-pore channels (TPCs) have also been ascribed with metabolic functionality, we studied the effect of simultaneously knocking out TPC1 and TPC2 on body composition and energy balance in male mice fed a chow diet. Compared with wild-type mice, TPC1 and TPC2 double knockout (Tpcn1/2(-/-)) animals had a higher respiratory quotient and became obese between 6 and 9 months of age. Although food intake was unaltered, interscapular brown adipose tissue (BAT) maximal temperature and lean-mass adjusted oxygen consumption were lower in Tpcn1/2(-/-) than in wild type mice. Phosphorylated hormone-sensitive lipase expression, lipid density and expression of β-adrenergic receptors were also lower in Tpcn1/2(-/-) BAT, whereas mitochondrial respiratory chain function and uncoupling protein-1 expression remained intact. We conclude that Tpcn1/2(-/-) mice show mature-onset obesity due to reduced lipid availability and use, and a defect in β-adrenergic receptor signaling, leading to impaired thermogenic activity, in BAT.
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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.