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Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice
Takahiro Fujimoto1, Kyoko Miyasaka, Midori Koyanagi
1Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Abstract:
Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP(-/-)) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP(-/-) mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia. Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP(-/-) mice is enhanced in an insulin-independent manner, suggesting that BAT is involved in altered energy homeostasis in KRAP(-/-) mice, although UCP (Uncoupling protein) expressions are not altered. Of interest is the down-regulation of fatty acid metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and fatty acid synthase in the liver of KRAP(-/-) mice, which could in part account for the metabolic phenotype in KRAP(-/-) mice. Thus, KRAP is a novel regulator in whole-body energy homeostasis and may be a therapeutic target in obesity and related diseases.
Insights
Ki-ras-induced actin-interacting protein (KRAP) deficiency enhances metabolic rate and protects against obesity. KRAP-deficient mice exhibit improved glucose tolerance and reduced adiposity, suggesting KRAP as a therapeutic target for metabolic disorders.
Area of Science:
- Metabolic disorders
- Obesity research
- Molecular biology
Background:
- Obesity and related metabolic disorders are major causes of adult morbidity and mortality.
- Ki-ras-induced actin-interacting protein (KRAP) is a ubiquitous cytoskeleton-associated protein with unknown physiological roles.
- KRAP was initially identified as a cancer-related molecule.
Purpose of the Study:
- To investigate the physiological roles of KRAP in whole-body energy homeostasis.
- To determine the effects of KRAP deficiency on metabolic parameters and diet-induced obesity.
- To explore KRAP as a potential therapeutic target for metabolic diseases.
Main Methods:
- Generation and analysis of KRAP-deficient (KRAP(-/-)) mice.
- Assessment of metabolic rate, adiposity, glucose tolerance, insulin, and leptin levels.
- Evaluation of response to high-fat diet-induced obesity and insulin resistance.
- Measurement of glucose uptake in brown adipose tissue (BAT) and expression of uncoupling proteins (UCPs).
- Analysis of fatty acid metabolism-related gene expression in the liver.
Main Results:
- KRAP(-/-) mice displayed enhanced metabolic rate, decreased adiposity, improved glucose tolerance, and lower insulin and leptin levels.
- KRAP(-/-) mice were protected against high-fat diet-induced obesity and insulin resistance, even with increased food intake (hyperphagia).
- Enhanced insulin-independent glucose uptake was observed in the brown adipose tissue (BAT) of KRAP(-/-) mice.
- Down-regulation of key fatty acid metabolism enzymes (ACC-1, ACC-2, fatty acid synthase) was noted in the liver of KRAP(-/-) mice.
Conclusions:
- KRAP plays a significant role as a novel regulator of whole-body energy homeostasis.
- KRAP deficiency confers protection against obesity and metabolic dysfunction.
- KRAP represents a potential therapeutic target for the treatment of obesity and associated metabolic disorders.
