ArticleThe Journal of biological chemistry2019
Sonic hedgehog signaling instigates high-fat diet-induced insulin resistance by targeting PPARγ stability.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- m6A Modified VCAN Promotes Glomerular Endothelial Cells Injury and Diabetic Nephropathy by SHH Pathway.Applied biochemistry and biotechnology · 2026Article
- Systemic Sonic Hedgehog Signaling Links Intestinal Nutrient Sensing With Sex-Specific Type 2 Diabetes Progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Genomic Insights into Abdominal and Intramuscular Fat Deposition in Chickens and Their Implications for Productivity Traits: A Systematic Review.Animals : an open access journal from MDPI · 2026Review
- Inhibition of bruton's tyrosine kinase directly alleviates pathogenic CD4+ T cell response via PPAR-γ signaling in autoimmune uveitis.Journal of neuroinflammation · 2025Article
- Research advances in intramuscular fat deposition and chicken meat quality: genetics and nutrition.Journal of animal science and biotechnology · 2025Review
- Review
- Does Childhood Obesity Trigger Neuroinflammation?Biomedicines · 2022Article
- Loss of Hilnc prevents diet-induced hepatic steatosis through binding of IGF2BP2.Nature metabolism · 2021Article
- Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.Advanced drug delivery reviews · 2021Review
- Cell-Intrinsic Tumorigenic Functions of PPARγ in Bladder Urothelial Carcinoma.Molecular cancer research : MCR · 2021Article
- Contribution of Smoothened Receptor Signaling in GABAergic Neurotransmission and Chloride Homeostasis in the Developing Rodent Brain.Frontiers in physiology · 2021Review
- Assessment of CircRNA Expression Profiles and Potential Functions in Brown Adipogenesis.Frontiers in genetics · 2021Article
- Whole transcriptome expression profiles in placenta samples from women with gestational diabetes mellitus.Journal of diabetes investigation · 2020Article
- Lipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury.Nature communications · 2020Article
- Peroxisome Proliferator Activated Receptor Gamma Sensitizes Non-small Cell Lung Carcinoma to Gamma Irradiation Induced Apoptosis.Frontiers in genetics · 2019Article
- Maternal obesity and developmental programming of neuropsychiatric disorders: An inflammatory hypothesis.Brain and neuroscience advancesReview
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity is a major risk for patients with chronic metabolic disorders including type 2 diabetes. Sonic hedgehog (Shh) is a morphogen that regulates the pancreas and adipose tissue formation during embryonic development. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily and one of the most important regulators of insulin action. Here, we evaluated the role and mechanism of Shh signaling in obesity-associated insulin resistance and characterized its effect on PPARγ. We showed that Shh expression was up-regulated in subcutaneous fat from obese mice. In differentiated 3T3-L1 and primary cultured adipocytes from rats, recombinant Shh protein and SAG (an agonist of Shh signaling) activated an extracellular signal-regulated kinase (ERK)-dependent noncanonical pathway and induced PPARγ phosphorylation at serine 112, which decreased PPARγ activity. Meanwhile, Shh signaling degraded PPARγ protein via binding of PPARγ to neural precursor cell-expressed developmentally down-regulated protein 4-1 (NEDD4-1). Furthermore, vismodegib, an inhibitor of Shh signaling, attenuated ERK phosphorylation induced by a high fat diet (HFD) and restored PPARγ protein level, thus ameliorating glucose intolerance and insulin resistance in obese mice. Our finding suggests that Shh in subcutaneous fat decreases PPARγ activity and stability via activation of an ERK-dependent noncanonical pathway, resulting in impaired insulin action. Inhibition of Shh may serve as a potential therapeutic approach to treat obesity-related diabetes.
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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.