ArticleMolecular metabolism2016
PI3K p110β subunit in leptin receptor expressing cells is required for the acute hypophagia induced by endotoxemia.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- IGF-1 and insulin receptors in LepRb neurons jointly regulate body growth, bone mass, reproduction, and metabolism.Molecular metabolism · 2026Article
- Tumor Necrosis Factor α and Interleukin-1β Acutely Inhibit AgRP Neurons in the Arcuate Nucleus of the Hypothalamus.International journal of molecular sciences · 2020Article
- Lack of AR in LepRb Cells Disrupts Ambulatory Activity and Neuroendocrine Axes in a Sex-Specific Manner in Mice.Endocrinology · 2020Article
- The Impact of Photoperiod on the Leptin Sensitivity and Course of Inflammation in the Anterior Pituitary.International journal of molecular sciences · 2020Article
- PI3K signalling in leptin receptor cells: Role in growth and reproduction.Journal of neuroendocrinology · 2019Review
- PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling.Endocrinology · 2019Review
- Insulin signaling in LepR cells modulates fat and glucose homeostasis independent of leptin.American journal of physiology. Endocrinology and metabolism · 2019Article
- PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction.JCI insight · 2017Article
- Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.Brain structure & function · 2017Article
- LPS-Induced Low-Grade Inflammation Increases Hypothalamic JNK Expression and Causes Central Insulin Resistance Irrespective of Body Weight Changes.International journal of molecular sciences · 2017Article
- Visceral Inflammation and Immune Activation Stress the Brain.Frontiers in immunology · 2017Review
- The Leptin Receptor Complex: Heavier Than Expected?Frontiers in endocrinology · 2017Review
- PI3K signaling: A molecular pathway associated with acute hypophagic response during inflammatory challenges.Molecular and cellular endocrinology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveHypophagia and increased energy expenditure under inflammatory conditions, such as that observed after bacterial lipopolysaccharide (LPS) administration, are associated with leptin secretion. The hypophagic effect of leptin depends in part on the activation of PI3K signaling pathway. However, the role of PI3K in the endotoxemia-induced hypophagia has not been determined.
methodsIn an attempt to examine the functional contribution of the PI3K pathway in hypophagia and weight loss induced by LPS (100 ug/Kg, ip), we performed a central pharmacological PI3K inhibition (LY294002). Additionally, to gain mechanistic insights on the role of the catalytic PI3K p110α subunit in leptin responsive cells, mice expressing Cre-recombinase driven by the Lepr promoter (LepR-Cre) were crossed with mice carrying a loxP-modified p110α allele (Pi3kca gene) (LepR(Δp110α)). As studies have suggested that the PI3K p110β subunit has a dominant role over p110α in energy homeostasis, we further crossed LepR-Cre mice with loxP-modified p110α and p110β (Pi3kcb gene) alleles (LepR(Δp110α+β)). In order to verify the requirement of leptin in PI3K effects on food intake, we also used leptin-deficient ob/ob mice.
resultsWe found that LPS stimulates PI3K and STAT3 signaling pathways in cells expressing the leptin receptor. Central PI3K inhibition prevented LPS-induced hypophagia and weight loss. Genetic deletion of p110α subunit selectively in LepR cells had no effect on LPS-induced hypophagia and weight loss. However, p110α and p110β double deletion in LepR cells prevented LPS-induced hypophagia and partially reversed the weight loss. Leptin deficiency blunted LPS-induced acute pAKT and pSTAT3 phosphorylation and the acute suppression of food intake.
conclusionsOur studies show that the PI3K p110β subunit in LepR cells is required for acute endotoxemic hypophagia. The data provide promising approaches for PI3K inhibition in preventing low energy balance and cachectic states during inflammatory challenges.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.