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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Protein kinase C deficiency increases fatty acid oxidation and reduces fat storage
Rishipal R Bansode1, Wei Huang1, Sanjit K Roy1
1Department of Molecular and Cellular Biochemistry, Columbus, Ohio 43210.
Abstract:
Metabolic syndrome is common in the general population, but there is little information available on the underlying signaling mechanisms regulating triglyceride (TG) content in the body. In the current study, we have uncovered a role for protein kinase Cbeta (PKCbeta) in TG homeostasis by studying the consequences of a targeted disruption of this kinase. PKCbeta(-/-) mutant mice were considerably leaner and the size of white fat depots was markedly decreased compared with wild-type littermates. TG content in the liver and skeletal muscle of PKCbeta(-/-) mice was also significantly low. Interestingly, mutant animals were hyperphagic and exhibited higher food intake and reduced feed efficiency versus wild type. The protection from obesity involves elevated oxygen consumption/energy expenditure and increased fatty acid oxidation in adipose tissue with concurrent increased mitochondria genesis, up-regulation of PGC-1alpha and UCP-2, and down-regulation of perilipin. The ability of PKCbeta deficiency to promote fat burning in adipocytes may suggest novel therapeutic strategies for obesity and obesity-related disorders.
Insights
Protein kinase Cbeta (PKCbeta) deficiency leads to leaner mice with reduced fat. This suggests PKCbeta plays a key role in regulating body triglyceride content and offers potential therapeutic targets for obesity.
Area of Science:
- Biochemistry
- Physiology
- Metabolic Research
Background:
- Metabolic syndrome is prevalent, yet mechanisms controlling body triglyceride (TG) levels are not fully understood.
- Protein kinase Cbeta (PKCbeta) is implicated in cellular signaling, but its role in whole-body TG homeostasis is unclear.
Purpose of the Study:
- To investigate the function of protein kinase Cbeta (PKCbeta) in regulating triglyceride homeostasis.
- To determine the physiological consequences of PKCbeta deficiency on body composition and energy metabolism.
Main Methods:
- Utilized PKCbeta knockout (PKCbeta(-/-)) mice and compared them to wild-type littermates.
- Assessed body weight, fat depot size, TG content in liver and muscle, food intake, and energy expenditure.
Main Results:
- PKCbeta(-/-) mice were significantly leaner with reduced white adipose tissue mass and lower TG levels in liver and skeletal muscle.
- Mutant mice exhibited hyperphagia but displayed reduced feed efficiency, indicating increased energy expenditure.
- Protection from obesity was linked to elevated oxygen consumption, enhanced fatty acid oxidation, increased mitochondrial biogenesis, PGC-1alpha and UCP-2 upregulation, and perilipin downregulation in adipocytes.
Conclusions:
- PKCbeta plays a critical role in maintaining triglyceride homeostasis and regulating body fat accumulation.
- PKCbeta deficiency enhances fat metabolism in adipocytes, suggesting potential therapeutic avenues for obesity and related metabolic disorders.
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