ArticleNature medicine2009
Molecular therapy of obesity and diabetes by a physiological autoregulatory approach.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Association between Obesity and Circulating Brain-Derived Neurotrophic Factor (BDNF) Levels: Systematic Review of Literature and Meta-Analysis.International journal of molecular sciences · 2018Pooled it
- Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients.Nutrition & diabetes · 2016Trial
- Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity.Molecular therapy. Advances · 2026Article
- Overactive bladder phenotype induced by chronic activation of hypothalamic neuroendocrine stress pathways in rats with no extrinsic behavioral stress applied.Scientific reports · 2025Article
- Hijacking homeostasis: the brain-body neural circuitry in tumor pathogenesis and emerging therapeutic frontiers.Molecular cancer · 2025Review
- Circulating microRNAs as Potential Biomarkers of Overweight and Obesity in Adults: A Narrative Review.Genes · 2025Review
- Environmental Enrichment Normalizes Metabolic Function in the Murine Model of Prader-Willi Syndrome Magel2-Null Mice.Endocrinology · 2025Article
- Interplay between the brain and adipose tissue: a metabolic conversation.EMBO reports · 2024Review
- Influence of the Brain-Derived Neurotrophic Factor Gene Polymorphism on Weight Loss Following Intragastric Balloon Intervention: A Cross-Sectional Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- AAV-BDNF gene therapy ameliorates a hypothalamic neuroinflammatory signature in theMolecular therapy. Methods & clinical development · 2023Article
- Regulation of Satiety byBiomolecules · 2023Article
- The Waist-Hip Ratio is a Mediator Between Serum Levels of Brain-Derived Neurotrophic Factor and Its Val66Met Polymorphism in Adolescents.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Hypothalamic TrkB.FL overexpression improves metabolic outcomes in the BTBR mouse model of autism.PloS one · 2023Article
- Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in theMolecular therapy. Methods & clinical development · 2022Article
- Reciprocal signaling between adipose tissue depots and the central nervous system.Frontiers in cell and developmental biology · 2022Review
- Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia.Frontiers in cardiovascular medicine · 2022Article
- Association of Circulating Brain-Derived Neurotrophic Factor with Cognition among Adult Obese Population.Journal of obesity & metabolic syndrome · 2021Article
- Enhancing Effects of Environmental Enrichment on the Functions of Natural Killer Cells in Mice.Frontiers in immunology · 2021Review
- Regulation of aging and cancer by enhanced environmental activation of a hypothalamic-sympathoneural-adipocyte axis.Translational cancer research · 2020Article
- Improvements to Healthspan Through Environmental Enrichment and Lifestyle Interventions: Where Are We Now?Frontiers in neuroscience · 2020Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hypothalamic brain-derived neurotrophic factor (BDNF) is a key element in the regulation of energy balance. Here we investigated the therapeutic efficacy of BDNF by gene transfer in mouse models of obesity and diabetes. Gene transfer of BDNF led to marked weight loss and alleviation of obesity-associated insulin resistance. To facilitate clinical translation and ensure that BDNF protein expression was appropriately decreased as weight loss progressed, thus preventing cachexia, we developed a molecular autoregulatory system involving a single recombinant adeno-associated virus vector harboring two expression cassettes, one constitutively driving BDNF and the other driving a specific microRNA targeting BDNF. The microRNA element was controlled by a promoter (that controlling the Agrp gene encoding agouti-related peptide) responsive to BDNF-induced physiological changes. Hence, as body weight decreased and agouti-related protein is induced, microRNA expression was activated, inhibiting transgene expression. In contrast to the progressive weight loss associated with a nonregulated approach, this microRNA-approach led to a sustainable plateau of body weight after notable weight loss was achieved. This strategy mimics the body's endogenous physiological feedback mechanisms, thereby resetting the hypothalamic set point to reverse obesity and metabolic syndrome.
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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.