ArticleNature communications2020
Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 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.
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Who cites it
43 citing papers in PubMed, 66 citations in OpenAlex.
- The perineurium integrates leptin with its sympathetic outflow to protect against obesity.Nature metabolism · 2026Article
- Multi-trait GWAS of reaction norm parameters reveals environment-responsive loci influencing reproductive performance in heifers.Journal of animal science and biotechnology · 2026Article
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
- Adipokine in Metabolic Liver Disease: Adipo-Brain-Liver Cross talk.International journal of endocrinology · 2026Review
- Serum SH2B1 and SULT1A2 in relation to adiposity and early weight-loss response: a hypothesis-generating study.Frontiers in endocrinology · 2026Article
- Genetic pleiotropy underlying obesity and autoimmune disorders: a large-scale cross-trait gwas analysis in European ancestry populations.Journal of translational medicine · 2025Article
- Integrating genetic and transcriptomic data to identify genes underlying obesity risk loci.International journal of obesity (2005) · 2025Article
- Molecular mechanisms and neural mediators of leptin action.Genes & development · 2025Review
- Article
- Impact of protein intake from a caloric-restricted diet on liver lipid metabolism in overweight and obese rats of different sexes.Scientific reports · 2025Article
- Review
- SH2B1 Defends Against Energy Imbalance, Obesity, and Metabolic Disease via a Paraventricular Hypothalamus→Dorsal Raphe Nucleus Neurocircuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Leptin receptor neurons in the ventral premammillary nucleus modulate emotion-induced insomnia.Cell discovery · 2024Article
- A Comprehensive Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features and Molecular Diagnosis.Current obesity reports · 2024Review
- AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation.Nature communications · 2024Article
- Effects of lifestyle factors on leukocytes in cardiovascular health and disease.Nature reviews. Cardiology · 2024Review
- Adipose Tissue, Non-Communicable Diseases, and Physical Exercise: An Imperfect Triangle.International journal of molecular sciences · 2023Review
- The Phenotypic variability of 16p11.2 distal BP2-BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples.Journal of medical genetics · 2023Article
- TLR4 in POMC neurons regulates thermogenesis in a sex-dependent manner.Journal of lipid research · 2023Article
- l-Type amino acid transporter 1 in hypothalamic neurons in mice maintains energy and bone homeostasis.JCI insight · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Leptin stimulates the sympathetic nervous system (SNS), energy expenditure, and weight loss; however, the underlying molecular mechanism remains elusive. Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component of a SNS/brown adipose tissue (BAT)/thermogenesis axis. LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, leading to reduced core body temperature and cold intolerance. The adipose SNS degenerates progressively in mutant mice after 8 weeks of age. Adult-onset ablation of Sh2b1 in the mediobasal hypothalamus also impairs the SNS/BAT/thermogenesis axis; conversely, hypothalamic overexpression of human SH2B1 has the opposite effects. Mice with either LepR neuron-specific or adult-onset, hypothalamus-specific ablation of Sh2b1 develop obesity, insulin resistance, and liver steatosis. In contrast, hypothalamic overexpression of SH2B1 protects against high fat diet-induced obesity and metabolic syndromes. Our results unravel an unrecognized LepR neuron Sh2b1/SNS/BAT/thermogenesis axis that combats obesity and metabolic disease.
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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.