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Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

Fan F, Cao Q, Wang C, Ma X, Shen C, Liu XW, Bu LP, Zou YZ, Hu K, Sun AJ, Ge JB - Acta Pharmacol. Sin. (2014)

Bottom Line: Serum ethanol and acetaldehyde levels and blood lipids were measured.Metabolomics was used to characterize the heart and serum metabolism profiles.Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

ABSTRACT

Aim: To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice.

Methods: Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles.

Results: Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles.

Conclusion: Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

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Effect of ALDH2 deficiency on ethanol and acetaldehyde accumulation post-alcohol consumption. (A) Alcohol concentration in mouse serum. At 4 weeks, 18% ethanol consumption significantly increased the level of blood ethanol in both WT and KO mice. (B) Acetaldehyde concentration in mouse serum. The ALDH2 knockout could induce an acetaldehyde elevation in the water group that was aggravated by alcohol stimulation. (C) Heart ALDH2 Western blot lines of each genotype treated with water or alcohol are presented. (D) Protein expression was measured with grayscale analysis of the blots, with GAPDH used as an internal control. n=7 for each group. Mean±SEM. bP<0.05 vs WT. eP<0.05 vs WT+Alcohol. hP<0.05 vs KO.
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fig2: Effect of ALDH2 deficiency on ethanol and acetaldehyde accumulation post-alcohol consumption. (A) Alcohol concentration in mouse serum. At 4 weeks, 18% ethanol consumption significantly increased the level of blood ethanol in both WT and KO mice. (B) Acetaldehyde concentration in mouse serum. The ALDH2 knockout could induce an acetaldehyde elevation in the water group that was aggravated by alcohol stimulation. (C) Heart ALDH2 Western blot lines of each genotype treated with water or alcohol are presented. (D) Protein expression was measured with grayscale analysis of the blots, with GAPDH used as an internal control. n=7 for each group. Mean±SEM. bP<0.05 vs WT. eP<0.05 vs WT+Alcohol. hP<0.05 vs KO.

Mentions: As a key enzyme of alcohol metabolism, ALDH2 dehydrates acetaldehyde to acetic acid, which is the rate-limiting step of alcohol degradation22. Acetaldehyde has been proven to be the most toxic metabolite of alcohol metabolism. The ethanol combined with acetaldehyde level can reflect the degree of alcohol intoxication23. The levels of ethanol and acetaldehyde from WT and ALDH2 KO mouse serum were measured. After consuming alcohol, the serum ethanol and acetaldehyde levels were both significantly elevated. The ethanol level was increased from 0.019%±0.008% to 0.043%±0.024% in the WT mice and from 0.014%±0.006% to 0.050%±0.016% in the KO mice (Figure 2A). The acetaldehyde level was increased to 1.29±0.11-fold in the WT alcohol-drinking mice compared with the non-alcohol-drinking WT mice and to 1.63±0.11-fold in the KO mice after alcohol consumption. Furthermore, the acetaldehyde level was higher in the KO mice than in the WT mice, even without alcohol stimulation (WT: 1.00±0.02 vs KO: 1.36±0.11-fold, P<0.05) (Figure 2B). After 7 weeks of alcohol drinking, ALDH2 protein expression was not significantly different in the WT mice compared with the non-drinking WT mice (Figure 2C and 2D). ALDH2 protein expression was almost non-detectable in the ALDH2-knockout mouse hearts. However, half of the WT heart protein levels in the immunoblot densitometry analysis might be due to the background band sampling technique (Figure 2C, 2D).


Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

Fan F, Cao Q, Wang C, Ma X, Shen C, Liu XW, Bu LP, Zou YZ, Hu K, Sun AJ, Ge JB - Acta Pharmacol. Sin. (2014)

Effect of ALDH2 deficiency on ethanol and acetaldehyde accumulation post-alcohol consumption. (A) Alcohol concentration in mouse serum. At 4 weeks, 18% ethanol consumption significantly increased the level of blood ethanol in both WT and KO mice. (B) Acetaldehyde concentration in mouse serum. The ALDH2 knockout could induce an acetaldehyde elevation in the water group that was aggravated by alcohol stimulation. (C) Heart ALDH2 Western blot lines of each genotype treated with water or alcohol are presented. (D) Protein expression was measured with grayscale analysis of the blots, with GAPDH used as an internal control. n=7 for each group. Mean±SEM. bP<0.05 vs WT. eP<0.05 vs WT+Alcohol. hP<0.05 vs KO.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4125715&req=5

fig2: Effect of ALDH2 deficiency on ethanol and acetaldehyde accumulation post-alcohol consumption. (A) Alcohol concentration in mouse serum. At 4 weeks, 18% ethanol consumption significantly increased the level of blood ethanol in both WT and KO mice. (B) Acetaldehyde concentration in mouse serum. The ALDH2 knockout could induce an acetaldehyde elevation in the water group that was aggravated by alcohol stimulation. (C) Heart ALDH2 Western blot lines of each genotype treated with water or alcohol are presented. (D) Protein expression was measured with grayscale analysis of the blots, with GAPDH used as an internal control. n=7 for each group. Mean±SEM. bP<0.05 vs WT. eP<0.05 vs WT+Alcohol. hP<0.05 vs KO.
Mentions: As a key enzyme of alcohol metabolism, ALDH2 dehydrates acetaldehyde to acetic acid, which is the rate-limiting step of alcohol degradation22. Acetaldehyde has been proven to be the most toxic metabolite of alcohol metabolism. The ethanol combined with acetaldehyde level can reflect the degree of alcohol intoxication23. The levels of ethanol and acetaldehyde from WT and ALDH2 KO mouse serum were measured. After consuming alcohol, the serum ethanol and acetaldehyde levels were both significantly elevated. The ethanol level was increased from 0.019%±0.008% to 0.043%±0.024% in the WT mice and from 0.014%±0.006% to 0.050%±0.016% in the KO mice (Figure 2A). The acetaldehyde level was increased to 1.29±0.11-fold in the WT alcohol-drinking mice compared with the non-alcohol-drinking WT mice and to 1.63±0.11-fold in the KO mice after alcohol consumption. Furthermore, the acetaldehyde level was higher in the KO mice than in the WT mice, even without alcohol stimulation (WT: 1.00±0.02 vs KO: 1.36±0.11-fold, P<0.05) (Figure 2B). After 7 weeks of alcohol drinking, ALDH2 protein expression was not significantly different in the WT mice compared with the non-drinking WT mice (Figure 2C and 2D). ALDH2 protein expression was almost non-detectable in the ALDH2-knockout mouse hearts. However, half of the WT heart protein levels in the immunoblot densitometry analysis might be due to the background band sampling technique (Figure 2C, 2D).

Bottom Line: Serum ethanol and acetaldehyde levels and blood lipids were measured.Metabolomics was used to characterize the heart and serum metabolism profiles.Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

ABSTRACT

Aim: To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice.

Methods: Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles.

Results: Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles.

Conclusion: Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

Show MeSH
Related in: MedlinePlus