CPT2
Carnitine O-palmitoyltransferase 2, mitochondrial precursor (EC 2.3.1.21) (Carnitine palmitoyltransferase II) (CPT II) [CPT1]
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We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high-fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high-fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n-6/n-3 ratio but significantly increased the n-3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF-κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
Keywords
- EGCG
- free fatty acid
- high-fat dietary
- lifespan
- proteomics
- transcriptome
The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Brain
- Carnitine O-Palmitoyltransferase
- Drosophila Proteins
- Drosophila melanogaster
- Energy Metabolism
- Homeostasis
- Humans
- Larva
- Lipid Droplets
- Lipid Metabolism
- Molecular Sequence Data
- Mutation
- Neuroglia
- Obesity
- Oxidation-Reduction
- Phospholipids
- RNA, Messenger
- Sequence Alignment
- Survival Analysis
- Triglycerides
Aging affects oxidative metabolism in liver and other tissues. Carnitine acyltransferases are key enzymes of this process in mitochondria. As previously shown, the rate of transcription and activity of carnitine palmitoyltransferase CPT1 are also related to carnitine levels. In this study we compared the effect of dietary l-carnitine (100 mg l-carnitine/kg body weight/day over 3 months) on liver enzymes of aged rats (months 21-24) to adult animals (months 6-9) and age-related controls for both groups. The transcription rate of CPT1, CPT2, and carnitine acetyltransferase (CRAT) was determined by quantitative reverse transcription real-time PCR (RTQPCR) and compared to the activity of the CPT1A enzyme. The results showed that the transcription rates of CPT1, CPT2, and CRAT were similar in aged and adult control animals. Carnitine-fed old rats had a significant (p<0.05) 8-12-fold higher mean transcription rate of CPT1 and CRAT compared to aged controls, adult carnitine-fed animals, and adult controls, whereas the transcription rate of CPT2 was stimulated 2-3-fold in carnitine-fed animals of both age groups. With regard to the enzymatic activity of CPT1 there was a 1.5-fold increase in the old carnitine group compared to all other groups. RNA in situ hybridization also indicated an enhanced expression of CPT1A in hepatocytes from l-carnitine-supplemented animals. These results suggest that l-carnitine stimulates transcription of CPT1, CPT2, and CRAT as well as the enzyme activity of CPT1 in the livers of aged rats.
MeSH Terms
- Aging
- Animals
- Carnitine
- Carnitine O-Acetyltransferase
- Carnitine O-Palmitoyltransferase
- Dietary Supplements
- Enzyme Activation
- In Situ Hybridization, Fluorescence
- Liver
- Male
- Rats
- Rats, Sprague-Dawley
- Reverse Transcriptase Polymerase Chain Reaction
- Transcription, Genetic