Research

16 pages, 4426 KiB

Open AccessArticle

Low-Dose Administration of Cannabigerol Attenuates Inflammation and Fibrosis Associated with Methionine/Choline Deficient Diet-Induced NASH Model via Modulation of Cannabinoid Receptor

by Nouf Aljobaily, Kelsey Krutsinger, Michael J. Viereckl, Raznin Joly, Bridger Menlove, Brexton Cone, Ailaina Suppes and Yuyan Han

Nutrients 2023, 15(1), 178; https://doi.org/10.3390/nu15010178 - 30 Dec 2022

Cited by 4 | Viewed by 2896

Abstract

Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD). NASH is distinguished by severe hepatic fibrosis and inflammation. The plant-derived, non-psychotropic compound cannabigerol (CBG) has potential anti-inflammatory effects similar to other cannabinoids. However, the impact of CBG on NASH [...] Read more.

Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD). NASH is distinguished by severe hepatic fibrosis and inflammation. The plant-derived, non-psychotropic compound cannabigerol (CBG) has potential anti-inflammatory effects similar to other cannabinoids. However, the impact of CBG on NASH pathology is still unknown. This study demonstrated the therapeutic potential of CBG in reducing hepatic steatosis, fibrosis, and inflammation. Methods: 8-week-old C57BL/6 male mice were fed with methionine/choline deficient (MCD) diet or control (CTR) diets for five weeks. At the beginning of week 4, mice were divided into three sub-groups and injected with either a vehicle, a low or high dose of CBG for two weeks. Overall health of the mice, Hepatic steatosis, fibrosis, and inflammation were evaluated. Results: Increased liver-to-body weight ratio was observed in mice fed with MCD diet, while a low dose of CBG treatment rescued the liver-to-body weight ratio. Hepatic ballooning and leukocyte infiltration were decreased in MCD mice with a low dose of CBG treatment, whereas the CBG treatment did not change the hepatic steatosis. The high dose CBG administration increased inflammation and fibrosis. Similarly, the expression of cannabinoid receptor (CB)1 and CB2 showed decreased expression with the low CBG dose but not with the high CBG dose intervention in the MCD group and were co-localized with mast cells. Additionally, the decreased mast cells were accompanied by decreased expression of transforming growth factor (TGF)-β1. Conclusions: Collectively, the low dose of CBG alleviated hepatic fibrosis and inflammation in MCD-induced NASH, however, the high dose of CBG treatment showed enhanced liver damage when compared to MCD only group. These results will provide pre-clinical data to guide future intervention studies in humans addressing the potential uses of CBG for inflammatory liver pathologies, as well as open the door for further investigation into systemic inflammatory pathologies. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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13 pages, 1406 KiB

Open AccessArticle

Ideal Cardiovascular Health Metrics Are Associated with Reduced Severity of Hepatic Steatosis and Liver Fibrosis Detected by Transient Elastography

by Heze Fan, Chenbo Xu, Wenyuan Li, Yuzhi Huang, Rui Hua, Ying Xiong, Yuxuan Yang, Xueying Feng, Zihao Wang, Zuyi Yuan and Juan Zhou

Nutrients 2022, 14(24), 5344; https://doi.org/10.3390/nu14245344 - 16 Dec 2022

Cited by 3 | Viewed by 2480

Abstract

Life’s Simple 7 (LS7) is the American Heart Association’s (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. [...] Read more.

Life’s Simple 7 (LS7) is the American Heart Association’s (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. We performed a cross-sectional study using the data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) cycle. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate the severity of hepatic steatosis and liver fibrosis and to define NAFLD, advanced liver fibrosis, and cirrhosis. A total of 2679 participants were included. Multivariate linear regression analysis revealed that per 1-unit increase in the CVH metric, CAP and LSM decreased by 8.565 units and 0.274 units, respectively. In the multivariate logistic regression analysis, the risk of NAFLD, advanced liver fibrosis, and cirrhosis were 7, 10, and 6 times higher in the poor CVH group than in the ideal CVH group. Subgroup analysis indicated that CVD patients and non-Hispanic whites could benefit more from ideal CVH. In conclusion, adherence to ideal CVH metrics, as proposed by the AHA, can significantly reduce the risk of hepatic steatosis and liver fibrosis. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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12 pages, 1422 KiB

Open AccessArticle

Fatty Liver Is an Independent Risk Factor for Elevated Intraocular Pressure

by Jun-Hyuk Lee, Yu-Jin Kwon, Hye Sun Lee, Jee Hye Han, Boyoung Joung and Sung Jin Kim

Nutrients 2022, 14(21), 4455; https://doi.org/10.3390/nu14214455 - 23 Oct 2022

Cited by 3 | Viewed by 2082

Abstract

Elevated intraocular pressure (EIOP) is a major risk factor for glaucoma. Both EIOP and fatty liver share metabolic risk factors, which implies a possible link between EIOP and fatty liver. We aimed to determine the association of fatty liver with EIOP and estimate [...] Read more.

Elevated intraocular pressure (EIOP) is a major risk factor for glaucoma. Both EIOP and fatty liver share metabolic risk factors, which implies a possible link between EIOP and fatty liver. We aimed to determine the association of fatty liver with EIOP and estimate the effect of fatty liver on EIOP directly and indirectly through insulin resistance. Data from 16,240 adults who underwent health examinations at a single center were analyzed. Multiple logistic regression analyses revealed that fully adjusted odds ratio (OR) and 95% confidence interval (CI) for EIOP in the fatty liver group compared to the non-fatty liver group were 1.36 and 1.08–1.71. Alcoholic liver disease was associated with EIOP in subgroup analysis (OR = 1.80, 95% CI: 1.27–2.56). There was a linear dose–response relationship between EIOP and the severity of fatty liver. Mediation analysis revealed that the total effect of fatty liver on intraocular pressure was 0.90 (0.81–0.99), with a direct effect of 0.81 (0.71–0.90) and an indirect effect of 0.09 (0.06–0.11) through insulin resistance. Fatty liver is independently associated with EIOP. It primarily has a direct effect on intraocular pressure. This suggests that evaluation of EIOP should be considered in patients with fatty liver. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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12 pages, 1522 KiB

Open AccessArticle

Is Hepatocellular Carcinoma in Fatty Liver Different to Non-Fatty Liver?

by Xuan-vinh Kevin Nguyen, Jason Zhang, Ken Lee Chin, Stephen Bloom and Amanda J. Nicoll

Nutrients 2022, 14(18), 3875; https://doi.org/10.3390/nu14183875 - 19 Sep 2022

Cited by 3 | Viewed by 1670

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in Australia and is recognised to play a role in the development of hepatocellular carcinoma (HCC). There are no clear guidelines regarding screening for HCC in NAFLD. The aim of [...] Read more.

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in Australia and is recognised to play a role in the development of hepatocellular carcinoma (HCC). There are no clear guidelines regarding screening for HCC in NAFLD. The aim of this retrospective study was to compare the characteristics and survival rates of NAFLD-HCC to patients with non-NAFLD-HCC to help guide future research in this area. Methods: A total of 152 HCC patients with either NAFLD (n = 36) or non-NAFLD (n = 116) were retrospectively analysed from the HCC database and medical records. Chi-square and independent t-test were used to compare baseline characteristics and Kaplan–Meier curves and Cox models were used for survival analysis. Results: Patients with NAFLD-HCC were more likely to be diagnosed due to symptoms rather than through screening, and at an older age, compared with non-NAFLD HCC. The median survival rates were lower in NAFLD-HCC (17.2 months) than in those with non-NAFLD-HCC (23.5 months). Conclusion: There is a rise in the number of HCC cases in patients with NAFLD, and this has significant implications for hepatologists as they are presented with more advanced diseases and have poorer outcomes. Future studies on HCC will need to identify this group earlier in order to have an impact on the HCC survival rate. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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14 pages, 300 KiB

Open AccessArticle

Hypertension and Associated Risk Factors among Children with Intellectual Disability: A Cross-Sectional Study

by Yan Sun, Rashmi Supriya, Yang Gao, Dan Tao, Siyue Yu, Aiwei Wang, Hardaway Chun-Kwan Chan, Xiaoting Ou, Jingjing Wang and Julien S. Baker

Nutrients 2022, 14(15), 3127; https://doi.org/10.3390/nu14153127 - 29 Jul 2022

Cited by 4 | Viewed by 1763

Abstract

To investigate the prevalence of hypertension and associated risk factors in Chinese children with intellectual disability, a cross-sectional study was conducted in a sample of 558 children with intellectual disability aged 6–18 years in Hong Kong, and 452 (81.0%) with valid data were [...] Read more.

To investigate the prevalence of hypertension and associated risk factors in Chinese children with intellectual disability, a cross-sectional study was conducted in a sample of 558 children with intellectual disability aged 6–18 years in Hong Kong, and 452 (81.0%) with valid data were included in the data analysis. Blood pressure was measured according to a standard protocol. Hypertension was defined using the age-, gender-, and height-specific classification criteria recommended by the 2018 Chinese Guidelines for Children. Multivariate and hierarchical logistic regression was fitted to examine the associations of hypertension with potential risk factors. Overall, 31.4% of the participants were classified as having hypertension. Obese children were more likely to develop hypertension than non-obese children (adjusted OR = 2.77, 95% CI: 1.28, 5.99, p = 0.010). A paternal education of college or above and a paternal occupation of clerks, sales representatives, and workers were also associated with an increased risk of hypertension. The prevalence of hypertension is high among Chinese children with intellectual disability. Obesity was the strongest risk factor. Further longitudinal studies are warranted to confirm our findings. Nevertheless, preventions against obesity are promising to receive doubled benefits in reducing both obesity and hypertension, given its strong relationship with hypertension in this special population. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

13 pages, 834 KiB

Open AccessArticle

Exploring the Path of Mediterranean Diet, Non-Alcoholic Fatty Liver Disease (NAFLD) and Inflammation towards 10-Year Cardiovascular Disease (CVD) Risk: The ATTICA Study 10-Year Follow-Up (2002–2012)

by Elena S. George, Ekavi N. Georgousopoulou, Duane D. Mellor, Christina Chrysohoou, Christos Pitsavos and Demosthenes B. Panagiotakos

Nutrients 2022, 14(12), 2367; https://doi.org/10.3390/nu14122367 - 07 Jun 2022

Cited by 5 | Viewed by 2697

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease, affecting ~30% of the population and increasing CVD. This study aimed to explore the direct, indirect and combined effects of Mediterranean diet, NAFLD and inflammation on the 10-year CVD risk [...] Read more.

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease, affecting ~30% of the population and increasing CVD. This study aimed to explore the direct, indirect and combined effects of Mediterranean diet, NAFLD and inflammation on the 10-year CVD risk in a healthy adult population. Methods: Using baseline and 10-year follow-up data from the ATTICA study, adherence to Mediterranean diet was measured using MedDietScore, and presence of NAFLD at baseline was assessed using the fatty liver index (FLI). Participants’ 10-year CVD outcomes were recorded and C-reactive protein (CRP) was used as a surrogate marker for inflammation. The direct and indirect roles of these factors were explored using logistic regression models and the pathways between them were analysed using a structural equation model (SEM). Results: NAFLD prevalence was 22.9% and its presence was 17% less likely for every unit increase in MedDietScore. NAFLD presence at baseline was associated with increased 10-year CVD incidence (39.4% vs. 14.5%, p = 0.002), but when adjusted for MedDietScore, NAFLD was not an independent predictor of 10-year CVD risk. MedDietScore was an independent protective factor of 10-year CVD risk (OR = 0.989, 95% CI: 0.847, 0.935), when adjusted for NAFLD at baseline, age, gender, sedentary lifestyle and other confounders. Further exploration using SEM showed that MedDietScore was associated with CVD risk directly even when inflammation as CRP was introduced as a potential mediator. Conclusion: FLI as a proxy measure of NAFLD is a strong predictor of 10-year CVD risk, and this prognostic relationship seems to be moderated by the level of adherence to Mediterranean diet. Adherence to Mediterranean diet remained an independent and direct CVD risk factor irrespective of NAFLD status and CRP. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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Review

Jump to: Research, Other

27 pages, 776 KiB

Open AccessEditor’s ChoiceReview

Understanding NAFLD: From Case Identification to Interventions, Outcomes, and Future Perspectives

by Daniel Clayton-Chubb, William Kemp, Ammar Majeed, John S. Lubel, Alex Hodge and Stuart K. Roberts

Nutrients 2023, 15(3), 687; https://doi.org/10.3390/nu15030687 - 29 Jan 2023

Cited by 13 | Viewed by 3316

Abstract

While non-alcoholic fatty liver disease (NAFLD) is a prevalent and frequent cause of liver-related morbidity and mortality, it is also strongly associated with cardiovascular disease-related morbidity and mortality, likely driven by its associations with insulin resistance and other manifestations of metabolic dysregulation. However, [...] Read more.

While non-alcoholic fatty liver disease (NAFLD) is a prevalent and frequent cause of liver-related morbidity and mortality, it is also strongly associated with cardiovascular disease-related morbidity and mortality, likely driven by its associations with insulin resistance and other manifestations of metabolic dysregulation. However, few satisfactory pharmacological treatments are available for NAFLD due in part to its complex pathophysiology, and challenges remain in stratifying individual patient’s risk for liver and cardiovascular disease related outcomes. In this review, we describe the development and progression of NAFLD, including its pathophysiology and outcomes. We also describe different tools for identifying patients with NAFLD who are most at risk of liver-related and cardiovascular-related complications, as well as current and emerging treatment options, and future directions for research. Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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Other

Jump to: Research, Review

2 pages, 179 KiB

Open AccessReply

Reply to Abenavoli et al. Comment on “Clayton-Chubb et al. Understanding NAFLD: From Case Identification to Interventions, Outcomes, and Future Perspectives. Nutrients 2023, 15, 687”

by Daniel Clayton-Chubb, William Kemp, Ammar Majeed, John S. Lubel, Alex Hodge and Stuart K. Roberts

Nutrients 2023, 15(13), 2908; https://doi.org/10.3390/nu15132908 - 27 Jun 2023

Viewed by 500

Abstract

Thank you for your interesting comment [...] Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

2 pages, 202 KiB

Open AccessComment

Comment on Clayton-Chubb et al. Understanding NAFLD: From Case Identification to Interventions, Outcomes, and Future Perspectives. Nutrients 2023, 15, 687

by Ludovico Abenavoli, Giuseppe La Torre and Natasa Milic

Nutrients 2023, 15(13), 2907; https://doi.org/10.3390/nu15132907 - 27 Jun 2023

Cited by 1 | Viewed by 623

Abstract

This letter is to comment on the article by Clayton-Chubb et al. on the pathogenesis of non-alcoholic fatty liver disease and its outcomes, and the description of current, emerging and future directions to treat this condition [...] Full article

(This article belongs to the Special Issue Liver Disease, Lifestyle and Cardiovascular Risk)

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