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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 knockout on survival status post-alcohol consumption in mice. (A) Four week survival curves of mice during ethanol consumption at final concentration (18%). The mice of the two water drinking groups and WT mice treated with alcohol all survived, but half (n=7) of the KO alcohol mice died at the end of experiment. (B, C, and D) BW, HW, and AW were all decreased in the KO alcohol mice compared with the WT alcohol mice. 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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fig1: Effect of ALDH2 knockout on survival status post-alcohol consumption in mice. (A) Four week survival curves of mice during ethanol consumption at final concentration (18%). The mice of the two water drinking groups and WT mice treated with alcohol all survived, but half (n=7) of the KO alcohol mice died at the end of experiment. (B, C, and D) BW, HW, and AW were all decreased in the KO alcohol mice compared with the WT alcohol mice. n=7 for each group. Mean±SEM. bP<0.05 vs WT. eP<0.05 vs WT+Alcohol. hP<0.05 vs KO.

Mentions: All wild type (WT) mice survived, whereas the survival rate was 50% in the ALDH2-knockout (KO) mice after 7 weeks of ethanol consumption (Figure 1A). There were no significant differences in basic criteria, such as body weight (BW), heart weight (HW) or weight of adipose tissue around the gonads (AW) between the WT and KO mice. After ethanol consumption, BW, HW and AW were all significantly lower in the KO group than in the WT group (BW: 28.2±2.2 vs 20.4±2.8 g, HW: 0.195±0.018 vs0.120±0.037 g, AW: 0.322±0.124 vs 0.127±0.096 g, all P<0.05) (Figure 1B–1D). These results indicated that the ALDH2 knockout induced the deterioration of basic characteristics during alcohol consumption. Echocardiography was performed on all of the mice from the four groups. There were no significant differences in heart function, as shown by ejection fraction (EF) and fractional shortening (FS) measurements, or in structure, as shown by the left ventricular posterior wall diastolic and systolic (LVPW; D&S), left ventricular anterior wall diastolic and systolic (LVAW; D&S) and left ventricular end-diastolic and systolic diameter (LVEDD & ESD) (Figure S1).


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 knockout on survival status post-alcohol consumption in mice. (A) Four week survival curves of mice during ethanol consumption at final concentration (18%). The mice of the two water drinking groups and WT mice treated with alcohol all survived, but half (n=7) of the KO alcohol mice died at the end of experiment. (B, C, and D) BW, HW, and AW were all decreased in the KO alcohol mice compared with the WT alcohol mice. 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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fig1: Effect of ALDH2 knockout on survival status post-alcohol consumption in mice. (A) Four week survival curves of mice during ethanol consumption at final concentration (18%). The mice of the two water drinking groups and WT mice treated with alcohol all survived, but half (n=7) of the KO alcohol mice died at the end of experiment. (B, C, and D) BW, HW, and AW were all decreased in the KO alcohol mice compared with the WT alcohol mice. n=7 for each group. Mean±SEM. bP<0.05 vs WT. eP<0.05 vs WT+Alcohol. hP<0.05 vs KO.
Mentions: All wild type (WT) mice survived, whereas the survival rate was 50% in the ALDH2-knockout (KO) mice after 7 weeks of ethanol consumption (Figure 1A). There were no significant differences in basic criteria, such as body weight (BW), heart weight (HW) or weight of adipose tissue around the gonads (AW) between the WT and KO mice. After ethanol consumption, BW, HW and AW were all significantly lower in the KO group than in the WT group (BW: 28.2±2.2 vs 20.4±2.8 g, HW: 0.195±0.018 vs0.120±0.037 g, AW: 0.322±0.124 vs 0.127±0.096 g, all P<0.05) (Figure 1B–1D). These results indicated that the ALDH2 knockout induced the deterioration of basic characteristics during alcohol consumption. Echocardiography was performed on all of the mice from the four groups. There were no significant differences in heart function, as shown by ejection fraction (EF) and fractional shortening (FS) measurements, or in structure, as shown by the left ventricular posterior wall diastolic and systolic (LVPW; D&S), left ventricular anterior wall diastolic and systolic (LVAW; D&S) and left ventricular end-diastolic and systolic diameter (LVEDD & ESD) (Figure S1).

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