{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T19:29:02Z","timestamp":1793820542345,"version":"4.6.1"},"reference-count":99,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,9]],"date-time":"2022-07-09T00:00:00Z","timestamp":1657324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD099813"],"award-info":[{"award-number":["R01HD099813"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21HD104028"],"award-info":[{"award-number":["R21HD104028"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Maternal obesity results in programmed offspring hyperphagia and obesity. The increased offspring food intake is due in part to the preferential differentiation of hypothalamic neuroprogenitor cells (NPCs) to orexigenic (AgRP) vs. anorexigenic (POMC) neurons. The altered neurogenesis may involve hypothalamic bHLH (basic helix\u2013loop\u2013helix) neuroregulatory factors (Hes1, Mash1, and Ngn3). Whilst the underlying mechanism remains unclear, it is known that mitochondrial function is critical for neurogenesis and is impacted by proinflammatory cytokines such as TNF\u03b1. Obesity is associated with the activation of inflammation and oxidative stress pathways. In obese pregnancies, increased levels of TNF\u03b1 are seen in maternal and cord blood, indicating increased fetal exposure. As TNF\u03b1 influences neurogenesis and mitochondrial function, we tested the effects of TNF\u03b1 and reactive oxidative species (ROS) hydrogen peroxide (H2O2) on hypothalamic NPC cultures from newborn mice. TNF\u03b1 treatment impaired NPC mitochondrial function, increased ROS production and NPC proliferation, and decreased the protein expression of proneurogenic Mash1\/Ngn3. Consistent with this, AgRP protein expression was increased and POMC was decreased. Notably, treatment with H2O2 produced similar effects as TNF\u03b1 and also reduced the protein expression of antioxidant SIRT1. The inhibition of STAT3\/NF\u03baB prevented the effects of TNF\u03b1, suggesting that TNF\u03b1 mediates its effects on NPCs via mitochondrial-induced oxidative stress that involves both signaling pathways.<\/jats:p>","DOI":"10.3390\/brainsci12070900","type":"journal-article","created":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T21:19:28Z","timestamp":1657487968000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["TNF\u03b1-Induced Oxidative Stress and Mitochondrial Dysfunction Alter Hypothalamic Neurogenesis and Promote Appetite Versus Satiety Neuropeptide Expression in Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Mina","family":"Desai","sequence":"first","affiliation":[{"name":"The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles at Harbor-UCLA, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsey","family":"Stiles","sequence":"additional","affiliation":[{"name":"Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana S.","family":"Torsoni","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas\u2014UNICAMP, Limeira 13484-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-5291","authenticated-orcid":false,"given":"Marcio A.","family":"Torsoni","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas\u2014UNICAMP, Limeira 13484-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orian S.","family":"Shirihai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"},{"name":"Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5500-404X","authenticated-orcid":false,"given":"Michael G.","family":"Ross","sequence":"additional","affiliation":[{"name":"The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles at Harbor-UCLA, Torrance, CA 90502, USA"},{"name":"Department of Obstetrics and Gynecology, Charles R. 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