Related Experiment Videos
Insulin resistance and lipodystrophy in mice lacking ribosomal S6 kinase 2
Karim El-Haschimi1, Scott D Dufresne, Michael F Hirshman
1Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Abstract:
The p90 ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase with high expression levels in adipose tissue. Numerous in vitro studies show that RSK2 is activated by a broad number of cellular stimuli and suggest that RSK2 is involved in the regulation of a variety of cellular processes. However, the physiological role of RSK2 still remains elusive. We therefore generated rsk2 knockout (KO) mice to better understand the function of RSK2 in vivo. Birth weights of RSK2 KO mice are normal, but the body weight is reduced with age, as compared with wild-type littermates. We found that the difference in body weight was largely caused by a specific loss of white adipose tissue that is accompanied by reduced serum levels of the adipocyte-derived peptide, leptin. KO mice also have impaired glucose tolerance and elevated fasting insulin and glucose levels that are restored following administration of low amounts of leptin, which do not affect food intake. We conclude that RSK2 plays a novel and an important role in regulation of adipose mass in mice and speculate that the reduction in fat tissue may negatively affect insulin sensitivity, as observed in human lipodystrophy, through reduced levels of adipocyte-derived factors, such as leptin.
Insights
p90 ribosomal S6 kinase 2 (RSK2) deficiency in mice reduces adipose tissue mass and impairs glucose tolerance. This suggests RSK2 is crucial for regulating body fat and metabolic health.
Area of Science:
- Biochemistry
- Physiology
- Metabolic Research
Background:
- p90 ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase highly expressed in adipose tissue.
- In vitro studies suggest RSK2 regulates various cellular processes, but its in vivo physiological role is unclear.
Purpose of the Study:
- To investigate the in vivo function of RSK2 using knockout (KO) mice.
- To elucidate the role of RSK2 in regulating adipose tissue mass and metabolic homeostasis.
Main Methods:
- Generation and analysis of rsk2 knockout (KO) mice.
- Assessment of body weight, adipose tissue mass, serum leptin levels, glucose tolerance, and insulin levels.
- Evaluation of leptin administration effects on KO mice.
Main Results:
- RSK2 KO mice exhibit reduced body weight with age, primarily due to loss of white adipose tissue.
- KO mice show decreased serum leptin levels, impaired glucose tolerance, and elevated fasting insulin and glucose.
- Leptin administration partially restored glucose homeostasis in KO mice without affecting food intake.
Conclusions:
- RSK2 plays a significant role in regulating adipose mass in mice.
- Reduced adipose tissue in RSK2 KO mice may lead to insulin sensitivity issues, similar to human lipodystrophy, via decreased adipocyte-derived factors like leptin.