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Published on: May 24, 2018
Rsk4 Mediates Brain FGF19 Signaling to Constrain Diet-Induced Obesity in Mice
Chaonan Li1,2, Kaiyue Gu1,2, Ying Huang1,2
1Institute of Metabolism and Health, Department of Pathophysiology, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, China.
Abstract:
Central administration of fibroblast growth factor-19 (FGF19) has been shown to reduce body weight in obese mice, but the underlying mechanisms remain largely unknown. Here, we show that ribosomal S6 kinase 4 (Rsk4) is required for FGF19 to counteract obesity. Rsk4 is predominantly expressed in hypothalamic neurons. While loss of Rsk4 has negligible effects on energy homeostasis under basal conditions, it exacerbates diet-induced obesity (DIO) in mice due to hyperphagia. These mice also exhibit glucose intolerance and insulin resistance. Reexpression of Rsk4 in mediobasal hypothalamic neurons largely reverses the metabolic abnormalities caused by Rsk4 deletion. We further show that central FGF19 administration suppresses food intake and reduces body weight in control mice, whereas these effects are markedly blunted in Rsk4 knockout mice. Collectively, these findings reveal that hypothalamic neuronal Rsk4 constrains DIO in mice, likely through its critical role in central FGF19 signaling.
Article Highlights:
Ribosomal S6 kinase 4 (Rsk4) is predominantly expressed in hypothalamic neurons. Rsk4 is negligible for maintaining energy homeostasis in mice. Loss of Rsk4 promotes diet-induced obesity and related metabolic disorders in mice. Rsk4 is required for central fibroblast growth factor-19 to reduce body weight in obese mice.
Insights
Ribosomal S6 kinase 4 (Rsk4) loss promotes obesity and metabolic issues in mice. Rsk4 is crucial for fibroblast growth factor-19 to regulate body weight.
Area of Science:
- Neuroendocrinology
- Metabolic research
- Obesity studies
Background:
- Ribosomal S6 kinase 4 (Rsk4) is primarily found in hypothalamic neurons.
- Rsk4's role in energy homeostasis was previously considered negligible.
- Understanding Rsk4's function is key to metabolic disease research.
Purpose of the Study:
- To investigate the role of Rsk4 in energy homeostasis and diet-induced obesity.
- To determine if Rsk4 influences the efficacy of fibroblast growth factor-19 (FGF19) signaling.
- To explore Rsk4 as a potential therapeutic target for obesity.
Main Methods:
- Utilized mouse models with Rsk4 deficiency.
- Administered high-fat diets to induce obesity.
- Assessed metabolic parameters and body weight changes.
- Investigated FGF19 signaling pathways in the hypothalamus.
Main Results:
- Loss of Rsk4 did not impair basal energy homeostasis but exacerbated diet-induced obesity.
- Rsk4 deficiency led to related metabolic disorders.
- Rsk4 is essential for central FGF19 to reduce body weight in obese mice.
Conclusions:
- Rsk4 plays a critical role in preventing diet-induced obesity.
- Rsk4 mediates the body weight-reducing effects of central FGF19.
- Targeting Rsk4 may offer a novel strategy for obesity treatment.
