Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice

Heintz, Melissa M.; Kumar, Ramiya; Maner-Smith, Kristal; Ortlund, Eric A.; Baldwin, William S.

doi:10.1155/2022/7122738

Cited by 9 publications

(11 citation statements)

References 71 publications

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“…On the other hand, different researchers described that the increased BMI factors had an directly proportionate connection with daily diet. 15,17 LDL cholesterol levels were found to be higher and HDL cholesterol levels to be lower in people with high BMI 5,7,13 . There was found to be no connection between gender and alterations in lipid profiles.…”

Section: Discussionmentioning

confidence: 93%

“…The distribution of dietary fatty acids appears to have a significant role in modulating the effects of carbohydrate restriction on LDL-C and HDL-C. 15,16 A quantitative meta-analysis of metabolic ward studies (395 dietary trials with a median duration of one month, among 129 groups of people) found that removing 60% of dietary cholesterol and substituting other fats for 60% of saturated fats would reduce total cholesterol (TC) by about 31 mg/dL, or 10-15% 10,12,16 , with LDL-C dropping by about 4/5 of this reduction. According to numerous research, increased fish diet is advised to increase intake of omega-3 fatty acids and to lower the risk of metabolic diseases 17,19 . No correlation between consumption of milk products and an elevated risk of CHD, stroke, or other heart and vascular illnesses was discovered in the observational study's findings, regardless of the amount of milk fat present.…”

Section: Discussionmentioning

confidence: 99%

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Lipid Profile Changes Among Male and Female Regarding their Body Mass Index and Diet a Comparative Cross-Sectional Study

Najeeb¹,

Kanwal²,

Aisha³

et al. 2023

PJMHS

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Objective: The hypothesis that body mass index and diet has direct influence on plasma lipids. The aims and objectives of present study were to highlight the relationship between, BMI, diet and components of lipid profile in male and female individuals. Study Design: This was a cross-sectional comparative study in which blood samples were collected from both male and female individuals. Place and Duration: Present study was conducted in medical units of Jinnah hospital Lahore, Services hospital Lahore and Bahawal Victoria hospital Bahawalpur from February 2022 to November 2022. Methodology: Total 500 individuals were divided into different groups such as Group-A with 100 normal individuals were control while in Group-B 100 male individuals of 30-45 years with low fat balanced diet, in Group-C 100 male individuals with fat rich imbalanced diet, in Group-D 100 female individuals of 30-45 years with low fat balanced diet whereas in Group-E 100 female individuals with fat rich imbalanced diet were selected and BMI, Cholesterol, Triglyceride, LDL and HDL levels were measured respectively. Results: The findings of present study indicated different levels of cholesterol, triglycerides, low density lipoproteins and high density lipoproteins with comparative significant (P≤0.05) changes in different groups as compared with control Group-A. A remarkable changes in cholesterol, triglycerides, LDL, HDL levels in Group-B and Group-C were seen (160.1±0.02, 112.1±0.01, 106.1±0.01, 40.1±0.01) (210.2±0.01, 152.1±0.02, 120.2±0.03, 37.4±0.01) respectively. While in Group-E as compared with Group-D the cholesterol, triglycerides, LDL, HDL levels (230.2±0.04, 192.1±0.02, 130.1±0.01, 42.1±0.02) (170.2±0.04, 112.1±0.02, 110.2±0.03, 50.4±0.01) were high as compared with the individuals of Group-D. Practical implication: The regular health awareness programs were not available for local population from health administration while lipid profile is directly proportional to the cardiac medical complications in all over the world. The main task of present study was to provide exact medical awareness to the people about diet related variations of cholesterol, triglycerides, LDL and HDL levels and ultimately it was concluded that dyslipidemia can occur in those with a normal BMI as well as those who are obese or overweight. Conclusion: The findings of current study were described that cholesterol, triglycerides, LDL and HDL levels have correlation with BMI and intake diet. Therefore comparative significant (P≤0.05) changes in fat rich imbalanced groups were seen as compared with low fat balanced diet groups. According to the findings of this study, dyslipidemia can occur in those with a normal BMI as well as those who are obese or overweight. Keywords: Body mass index, Cholesterol, Triglycerides, Low density lipoproteins, High density lipoproteins

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Lipid Profile Changes Among Male and Female Regarding their Body Mass Index and Diet a Comparative Cross-Sectional Study

Najeeb¹,

Kanwal²,

Aisha³

et al. 2023

PJMHS

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“…Previous studies suggest that CYP2B6 has the ability to metabolize EtOH, but these studies did not further characterize how CYP2B6 regulates EtOH metabolism (Busby et al, 1999;Hamitouche et al, 2006;Vuppugalla et al, 2007) (Damiri & Baldwin, 2018;Heintz et al, 2019Heintz et al, , 2020Heintz et al, , 2022. In addition, studies using conditional P450 oxioreductase (POR) mice and Cyp2b-knockdown mice provided evidence that CYP2B enzymes are likely involved in unsaturated fatty acid metabolism (Damiri & Baldwin, 2018;Finn et al, 2009) mice.…”

Section: Discussionmentioning

confidence: 99%

“…While the increased EtOH concentrations in Cyp2b10 KO mice may contribute to the increased liver injury, CYP2B enzymes are known to play other physiological roles. Studies in Cyp2b ‐knockdown and null mice have shown that CYP2B enzymes have sexually dimorphic effects on lipid homeostasis, with male Cyp2b ‐knockdown/null mice gaining more weight on HFD (Damiri & Baldwin, 2018; Heintz et al, 2019, 2020, 2022). In addition, studies using conditional P450 oxioreductase (POR) mice and Cyp2b ‐knockdown mice provided evidence that CYP2B enzymes are likely involved in unsaturated fatty acid metabolism (Damiri & Baldwin, 2018; Finn et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Hepatic CYP2B10 is highly induced by binge ethanol and contributes to acute‐on‐chronic alcohol‐induced liver injury

Mackowiak

Lin

et al. 2022

Alcoholism Clin & Exp Res

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Background The chronic‐plus‐binge model of ethanol consumption, where chronically (8‐week) ethanol‐fed mice are gavaged a single dose of ethanol (E8G1), is known to induce steatohepatitis in mice. However, how chronically ethanol‐fed mice respond to multiple binges of ethanol remains unknown. Methods We extended the E8G1 model to three gavages of ethanol (E8G3) spaced 24 h apart, sacrificed each group 9 h after the final gavage, analyzed liver injury, and examined gene expression changes using microarray analyses in each group to identify mechanisms contributing to liver responses to binge ethanol. Results Surprisingly, E8G3 treatment induced lower levels of liver injury, steatosis, inflammation, and fibrosis as compared to mice after E8G1 treatment. Microarray analyses identified several pathways that may contribute to the reduced liver injury after E8G3 treatment compared to E8G1 treatment. The gene encoding cytochrome P450 2B10 (Cyp2b10) was one of the top upregulated genes in the E8G1 group and was further upregulated in the E8G3 group, but only moderately induced after chronic ethanol consumption, as confirmed by RT‐qPCR and western blot analyses. Genetic disruption of Cyp2b10 worsened liver injury in E8G1 and E8G3 mice with higher blood ethanol levels compared to wild‐type control mice, while in vitro experiments revealed that CYP2b10 did not directly promote ethanol metabolism. Metabolomic analyses revealed significant differences in hepatic metabolites from E8G1‐treated Cyp2b10 knockout and WT mice, and these metabolic alterations may contribute to the reduced liver injury in Cyp2b10 knockout mice. Conclusion Hepatic Cyp2b10 expression is highly induced after ethanol binge, and such upregulation reduces acute‐on‐chronic ethanol‐induced liver injury via the indirect modification of ethanol metabolism.

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“…Three recent studies found Cyp2b9 exhibited the highest increase in gene expression following a high-fat diet (HFD) in mice [ 8 – 10 ]. Our previously generated Cyp2b9/10/13-null (Cyp2b-null) mice are age- and diet-induced obese (DIO) with increased NAFLD in males [ 10 , 11 ]. Similarly, age-dependent lipid accumulation was observed in RNAi-mediated Cyp2b-knockdown male mice [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity

et al. 2022

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Multiple factors in addition to over consumption lead to obesity and non-alcoholic fatty liver disease (NAFLD) in the United States and worldwide. CYP2B6 is the only human detoxification CYP whose loss is associated with obesity, and Cyp2b-null mice show greater diet-induced obesity with increased steatosis than wildtype mice. However, a putative mechanism has not been determined. LC-MS/MS revealed that CYP2B6 metabolizes PUFAs, with a preference for metabolism of ALA to 9-HOTrE and to a lesser extent 13-HOTrE with a preference for metabolism of PUFAs at the 9- and 13-positions. To further study the role of CYP2B6 in vivo, humanized-CYP2B6-transgenic (hCYP2B6-Tg) and Cyp2b-null mice were fed a 60% high-fat diet for 16 weeks. Compared to Cyp2b-null mice, hCYP2B6-Tg mice showed reduced weight gain and metabolic disease as measured by glucose tolerance tests, however hCYP2B6-Tg male mice showed increased liver triglycerides. Serum and liver oxylipin metabolite concentrations increased in male hCYP2B6-Tg mice, while only serum oxylipins increased in female hCYP2B6-Tg mice with the greatest increases in LA oxylipins metabolized at the 9 and 13-positions. Several of these oxylipins, specifically 9-HODE, 9-HOTrE, and 13-oxoODE, are PPAR agonists. RNA-seq data also demonstrated sexually dimorphic changes in gene expression related to nuclear receptor signaling, especially CAR > PPAR with qPCR suggesting PPARγ signaling is more likely than PPARα signaling in male mice. Overall, our data indicates that CYP2B6 is an anti-obesity enzyme, but probably to a lesser extent than murine Cyp2b’s. Therefore, the inhibition of CYP2B6 by xenobiotics or dietary fats can exacerbate obesity and metabolic disease potentially through disrupted PUFA metabolism and the production of key lipid metabolites.

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Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice

Cited by 9 publications

References 71 publications

Lipid Profile Changes Among Male and Female Regarding their Body Mass Index and Diet a Comparative Cross-Sectional Study

Lipid Profile Changes Among Male and Female Regarding their Body Mass Index and Diet a Comparative Cross-Sectional Study

Hepatic CYP2B10 is highly induced by binge ethanol and contributes to acute‐on‐chronic alcohol‐induced liver injury

Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity

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