ArticleNature communications2024
Regulation of leptin signaling and diet-induced obesity by SEL1L-HRD1 ER-associated degradation in POMC expressing neurons.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Exercise and nutrition as epigenetic regulators of gene expression: an exploratory scoping review with bibliometric analysis.Frontiers in nutrition · 2026Pooled it
- Cross-Study Meta-Analysis of Blood Transcriptomes in Type 2 Diabetes.International journal of molecular sciences · 2025Pooled it
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Article
- The microbiota-gut-brain axis: novel mechanisms and therapeutic frontiers in obesity and type 2 diabetes.NPJ biofilms and microbiomes · 2026Review
- Neuronal SEL1L-HRD1 ER-associated degradation is essential for motor function and survival in mice.The Journal of clinical investigation · 2026Article
- SEL1L-HRD1 ERAD-autophagy interplay maintains mitochondrial homeostasis in brown adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional integrity of the SEL1L-HRD1 complex is critical for endoplasmic reticulum-associated degradation and organismal viability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Food additives with aldehyde skeleton exhibited leptin resistance in cells.Frontiers in nutrition · 2026Article
- SEL1L regulates ER homeostasis in Sertoli cells but is dispensable for their function.Molecular biology of the cell · 2025Article
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- Obesity's systemic impact: exploring molecular and physiological links to diabetes, cardiovascular disease, and heart failure.Frontiers in endocrinology · 2025Review
- Exploring the therapeutic potential of precision medicine in rare genetic obesity disorders: a scientific perspective.Frontiers in nutrition · 2024Review
Corrections and comments
- Update of
Authors and funding
4 authors.
Funding
Abstract
Endoplasmic reticulum (ER) homeostasis in the hypothalamus has been implicated in the pathogenesis of diet-induced obesity (DIO) and type 2 diabetes; however, the underlying molecular mechanism remain vague and debatable. Here we report that SEL1L-HRD1 protein complex of the highly conserved ER-associated protein degradation (ERAD) machinery in POMC-expressing neurons ameliorates diet-induced obesity and its associated complications, partly by regulating the turnover of the long isoform of Leptin receptors (LepRb). Loss of SEL1L in POMC-expressing neurons attenuates leptin signaling and predisposes mice to HFD-associated pathologies including fatty liver, glucose intolerance, insulin and leptin resistance. Mechanistically, nascent LepRb, both wildtype and disease-associated Cys604Ser variant, are misfolding prone and bona fide substrates of SEL1L-HRD1 ERAD. In the absence of SEL1L-HRD1 ERAD, LepRb are largely retained in the ER, in an ER stress-independent manner. This study uncovers an important role of SEL1L-HRD1 ERAD in the pathogenesis of central leptin resistance and leptin signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.