ArticleDiabetes2017
Adipocyte-Specific Deficiency of De Novo Sphingolipid Biosynthesis Leads to Lipodystrophy and Insulin Resistance.
Article in Diabetes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 62 citations in OpenAlex.
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- Characterization of SPTLC2 as a key driver promoting microglial activation and energy metabolism reprogramming after ischemic stroke through bulk and single-cell analyses combined with experimental validation.Cell biology and toxicology · 2025Article
- Mild Mitochondrial Uncoupling for True Ectopic Lipid Disposal.International journal of molecular sciences · 2025Review
- The enzyme SMPDL3b in podocytes decouples proteinuria from chronic kidney disease progression in experimental Alport Syndrome.Kidney international · 2025Article
- Latitude-driven adaptive evolution of body length in diverse pig breeds across China.BMC biology · 2025Article
- Deciphering Mechanisms of Adipocyte Differentiation in Abdominal Fat of Broilers.Journal of agricultural and food chemistry · 2024Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Inhibiting Phosphatidylcholine Remodeling in Adipose Tissue Increases Insulin Sensitivity.Diabetes · 2023Article
- Lipid remodeling of adipose tissue in metabolic health and disease.Experimental & molecular medicine · 2023Review
- Effect of Total SMS Activity on LDL Catabolism in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- ORMDL in metabolic health and disease.Pharmacology & therapeutics · 2023Review
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- Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.Nature communications · 2022Article
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- You aren't IMMUNE to the ceramides that accumulate in cardiometabolic disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Insulin Resistance: From Mechanisms to Therapeutic Strategies.Diabetes & metabolism journal · 2022Review
- Cholesterol - the devil you know; ceramide - the devil you don't.Trends in pharmacological sciences · 2021Review
- Sphingolipids in metabolic disease: The good, the bad, and the unknown.Cell metabolism · 2021Review
- Novel insights into the pathological mechanisms of metabolic related dyslipidemia.Molecular biology reports · 2021Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes. Adipocyte-specific SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass. Fatty acids that were destined for the adipose tissue were instead shunted to liver and caused hepatosteatosis. This impaired fat distribution caused systemic insulin resistance and hyperglycemia, indicating severe lipodystrophy. Mechanistically, sphingosine 1-phosphate (S1P) was reduced in the adipose tissues of aSPTLC2 KO mice, and this inhibited adipocyte proliferation and differentiation via the downregulation of S1P receptor 1 and decreased activity of the peroxisome proliferator-activator receptor γ. In addition, downregulation of SREBP (sterol regulatory element-binding protein)-1c prevented adipogenesis of aSPTLC2 KO adipocytes. Collectively, our observations suggest that the tight regulation of de novo sphingolipid biosynthesis and S1P signaling plays an important role in adipogenesis and hepatosteatosis.
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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.