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Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation
Open accessAbstract
The contribution of different leptin-induced signaling pathways in control of energy homeostasis is only partly understood. Here we show that selective Pten ablation in leptin-sensitive neurons (Pten(DeltaObRb)) results in enhanced Pi3k activation in these cells and reduces adiposity by increasing energy expenditure. White adipose tissue (WAT) of Pten(DeltaObRb) mice shows characteristics of brown adipose tissue (BAT), reflected by increased mitochondrial content and Ucp1 expression resulting from enhanced leptin-stimulated sympathetic nerve activity (SNA) in WAT. In contrast, leptin-deficient ob/ob-Pten(DeltaObRb) mice exhibit unaltered body weight and WAT morphology compared to ob/ob mice, pointing to a pivotal role of endogenous leptin in control of WAT transdifferentiation. Leanness of Pten(DeltaObRb) mice is accompanied by enhanced sensitivity to insulin in skeletal muscle. These data provide direct genetic evidence that leptin-stimulated Pi3k signaling in the CNS regulates energy expenditure via activation of SNA to perigonadal WAT leading to BAT-like differentiation of WAT.
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“Selective PTEN ablation in leptin-expressing neurons results in a phenotype characterized by reduced adiposity and increased energy expenditure due, at least in part, to increased fatty acid oxidation in WAT (144)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [144]
In the citing paper
“associated with increased sympathetic nerve activity to WAT and leading to a remodeling of WAT to take on characteristics of BAT, including increased mitochondrial content and UCP1 expression (144).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [144]
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Self-citationInsulin and leptin oscillations license food-entrained browning and metabolic flexibility
Mattar, P., Reginato, A., Lavados, C., Das, D., Kalyani, M., Martínez-López, N., Sharma, M., Skovbjerg, G., Skytte, J. L., Roostalu, U., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114390 · Cited by 6
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Inter-Organ Communication Involved in Brown Adipose Tissue Thermogenesis
Takahashi, K., Yamada, T., & Katagiri, H. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-981-97-4584-5_11 · Cited by 8
STAT3 but Not ERK2 Is a Crucial Mediator Against Diet-Induced Obesity via VMH Neurons
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“Each one of these signaling pathways has been shown to play an important role in the control of energy balance in several genetically modified mouse models: deletion of STAT3 in LepR-expressing neurons induces extreme obesity (5); deletion of SHP2, a protein that mediates the activation of ERK1/2 via LepR, induces ear…”
BackgroundBakuchiol ameliorates glycolipid homeostasis by reducing inflammation
Liu, Z., Xu, X., Liang, Z., Chen, Y., Wang, Q., Kang, W., Zhang, Y., & Cong, B. (2024) · Food Science and Human Wellness · doi:10.26599/fshw.2023.9250052 · Cited by 5
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Self-citationInter-organ communications mediate crosstalk between glucose and energy metabolism
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“Therefore, Saito et al. hypothesized that ectopic UCP1 expression in WAT can affect hypothalamic leptin sensitivity.”
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Elsaid, S., Jaume, A., & Najjar, S. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133231 · Cited by 2
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“How sex-differential expression of these genes are established, and whether their expressions are maintained by hormone or other factors are still unclear (Burke et al, 2016; Plum et al, 2007).”
BackgroundAssessing the role of PTEN in cholinergic neurons in glucose and energy homeostasis
Rapps, J. A. (2018) · TSpace (University of Toronto)
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Tsou, R. C. (2014) · Scholarly Commons (University of Pennsylvania)
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Self-citationParticipação da via da PI3K em neurônios SF1 do hipotálamo na homeostase energética
de Jesus, A. A. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2023.tde-08022024-155611
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Metadata
- Authors
- Plum, L., Rother, E., Münzberg, H., Wunderlich, F. T., Morgan, D. A., Hampel, B., Shanabrough, M., Janoschek, R., Könner, A. C., Alber, J., Suzuki, A., Krone, W., Horvath, T. L., Rahmouni, K., & Brüning, J. C.
- Affiliations
- University of Cologne (DE)
- University of Michigan (US)
- University of Iowa (US)
- Yale University (US)
- Akita University (JP)
- Corresponding author
- Brüning, Jens C.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 6
- Issue
- 6
- Pages
- 431-445
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2160824260
- Cited by
- 138
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 4 · 2021: 13 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 8 · 2012: 11
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, PI3K signaling, PTEN, white adipose tissue, energy expenditure, sympathetic activity, leptin receptor neurons, ob/ob mice, insulin sensitivity, skeletal muscle, mitochondrial content, UCP1, energy homeostasis
- MeSH terms
- Animals, Adipose Tissue, Brown, Central Nervous System, Enzyme Activation, Glucose, Mice, Mutant Strains, Mice, Obese, Mice, Transgenic, Thinness, Signal Transduction, Mice, Knockout, Phosphatidylinositol 3-Kinases, Leptin, PTEN Phosphohydrolase, Mice, Adipose Tissue, White, Cell Transdifferentiation
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