ArticleDiabetes2017
Rheb Inhibits Beiging of White Adipose Tissue via PDE4D5-Dependent Downregulation of the cAMP-PKA Signaling Pathway.
Article in Diabetes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Resveratrol ameliorates high‑fat diet‑induced insulin resistance via the DDIT4/mTOR pathway in skeletal muscle.Biomedical reports · 2025Article
- mTORC1 in energy expenditure: consequences for obesity.Nature reviews. Endocrinology · 2024Review
- Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9.iScience · 2024Article
- Vertical sleeve gastrectomy-derived gut metabolite licoricidin activates beige fat thermogenesis to combat obesity.Theranostics · 2023Article
- San Antonio Nathan Shock Center: your one-stop shop for aging research.GeroScience · 2021Article
- Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling.The Journal of experimental medicine · 2021Article
- Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice.Frontiers in pharmacology · 2021Article
- Article
- Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin.BMC pharmacology & toxicology · 2020Article
- Targeted Proteomic Analysis of Small GTPases in Murine Adipogenesis.Analytical chemistry · 2020Article
- A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure.Clinical science (London, England : 1979) · 2020Review
- Mitochondrial stress protein HSP60 regulates ER stress-induced hepatic lipogenesis.Journal of molecular endocrinology · 2020Article
- Review
- Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway.Journal of molecular cell biology · 2019Article
- mTOR signaling in Brown and Beige adipocytes: implications for thermogenesis and obesity.Nutrition & metabolism · 2019Review
- Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Roflumilast enhances cisplatin-sensitivity and reverses cisplatin-resistance of ovarian cancer cells via cAMP/PKA/CREB-FtMt signalling axis.Cell proliferation · 2018Article
- Adipose mTORC1 Suppresses Prostaglandin Signaling and Beige Adipogenesis via the CRTC2-COX-2 Pathway.Cell reports · 2018Article
- Combined QTL and Genome Scan Analyses With the Help of 2b-RAD Identify Growth-Associated Genetic Markers in a New Fast-Growing Carp Strain.Frontiers in genetics · 2018Article
- ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Beiging of white adipose tissue has potential antiobesity and antidiabetes effects, yet the underlying signaling mechanisms remain to be fully elucidated. Here we show that adipose-specific knockout of Rheb, an upstream activator of mechanistic target of rapamycin complex 1 (mTORC1), protects mice from high-fat diet-induced obesity and insulin resistance. On the one hand, Rheb deficiency in adipose tissue reduced mTORC1 signaling, increased lipolysis, and promoted beiging and energy expenditure. On the other hand, overexpression of Rheb in primary adipocytes significantly inhibited CREB phosphorylation and uncoupling protein 1 (UCP1) expression. Mechanistically, fat-specific knockout of Rheb increased cAMP levels, cAMP-dependent protein kinase (PKA) activity, and UCP1 expression in subcutaneous white adipose tissue. Interestingly, treating primary adipocytes with rapamycin only partially alleviated the suppressing effect of Rheb on UCP1 expression, suggesting the presence of a novel mechanism underlying the inhibitory effect of Rheb on thermogenic gene expression. Consistent with this notion, overexpression of Rheb stabilizes the expression of cAMP-specific phosphodiesterase 4D5 (PDE4D5) in adipocytes, whereas knockout of Rheb greatly reduced cellular levels of PDE4D5 concurrently with increased cAMP levels, PKA activation, and UCP1 expression. Taken together, our findings reveal Rheb as an important negative regulator of beige fat development and thermogenesis. In addition, Rheb is able to suppress the beiging effect through an mTORC1-independent mechanism.
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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.