Central leptin action improves skeletal muscle AKT, AMPK, and PGC1α activation by hypothalamic PI3K-dependent mechanism
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Central leptin action requires PI3K activity to modulate glucose homeostasis and peripheral metabolism. However, the mechanism behind this phenomenon is not clearly understood. We hypothesize that hypothalamic PI3K activity is important for the modulation of the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway, PGC1 alpha, and AKT in skeletal muscle (SM). To address this issue, we injected leptin into the lateral ventricle of rats. Hypothalamic JAK2 and AKT were activated by intracerebroventricular (ICV) injection of leptin in a time-dependent manner. Central leptin improved tolerance to glucose (GTT), increased PGC1 alpha expression, and AKT, AMPK, ACC and JAK2 phosphorylation in the soleus muscle. Previous ICV administration of either LY294002 or propranolol (IP) blocked these effects. We concluded that the activation of the hypothalamic PI3K pathway is important for leptin-induced AKT phosphorylation, as well as for active catabolic pathway through AMPK and PGC1 alpha in SM. Thus, a defective leptin signalling PI3K pathway in the hypothalamus may contribute to peripheral resistance to insulin associated to diet-induced obesity.
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The mechanism of leptin action also appears to be related to increases in physiological malonyl-CoA in the arcuate nucleus, which promotes a reduction in food intake and body weight, using different mechanisms from those previously reported for ghrelin action, during energetically wealthy states.
“The mechanism of leptin action also appears to be related to increases in physiological malonyl-CoA in the arcuate nucleus, which promotes a reduction in food intake and body weight, using different mechanisms to those previously reported for ghrelin action, during energetically wealthy states ([49](#B49), [141](#B141)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [141]
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- Authors
- Roman, E. A. F. R., Reis, D., Romanatto, T., Maimoni, D., Ferreira, E. A., Santos, G. A., Torsoni, A. S., Velloso, L. A., & Torsoni, M. A.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Universidade Braz Cubas (BR)
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 314
- Issue
- 1
- Pages
- 62-69
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W1979220770
- Cited by
- 71
- References
- 62
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 6
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- hypothalamus, PI3K signaling, Akt phosphorylation, AMPK, PGC-1α, acetyl-CoA carboxylase, skeletal muscle, glucose tolerance, insulin resistance, diet-induced obesity, JAK2, intracerebroventricular administration, LY294002, propranolol
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Phosphoinositide-3 Kinase Inhibitors, Adrenergic beta-Antagonists, Animals, Chromones, Energy Metabolism, Glucose, Homeostasis, Hypothalamus, Insulin, Male, Morpholines, Propranolol, Transcription Factors, Signal Transduction, RNA-Binding Proteins, Rats, Wistar, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Leptin, Proto-Oncogene Proteins c-akt, Rats, Janus Kinase 2, AMP-Activated Protein Kinases
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