Nutrients

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12 pages, 514 KiB

Open AccessArticle

The Impact of Japanese Dietary Patterns on Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis

by Takafumi Sasada, Chikara Iino, Satoshi Sato, Tetsuyuki Tateda, Go Igarashi, Kenta Yoshida, Kaori Sawada, Tatsuya Mikami, Shigeyuki Nakaji, Hirotake Sakuraba and Shinsaku Fukuda

Nutrients 2024, 16(17), 2877; https://doi.org/10.3390/nu16172877 - 28 Aug 2024

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Abstract

This study aimed to investigate the effect of Japanese dietary patterns on metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. After excluding factors affecting the diagnosis of hepatic steatosis, 727 adults were analyzed as part of the Health Promotion Project. The dietary [...] Read more.

This study aimed to investigate the effect of Japanese dietary patterns on metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. After excluding factors affecting the diagnosis of hepatic steatosis, 727 adults were analyzed as part of the Health Promotion Project. The dietary patterns of the participants were classified into rice, vegetable, seafood, and sweet based on their daily food intake. Liver stiffness measurements and controlled attenuation parameters were performed using FibroScan. Energy and nutrient intake were calculated using the Brief-type Self-administered Diet History Questionnaire. Univariate and multivariate analyses were used to identify the risk factors for liver fibrosis within the MASLD population. The vegetable group had significantly lower liver fibrosis indicators in the MASLD population than the rice group. The multivariate analysis identified a body mass index ≥ 25 kg/m² (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.01–1.83; p = 0.047) and HOMA-IR ≥ 1.6 (OR, 3.18; 95% CI, 1.74–5.78; p < 0.001) as risk factors for liver fibrosis, and vegetable group membership was a significant low-risk factor (OR, 0.38; 95% CI, 0.16–0.88; p = 0.023). The multivariate analysis of nutrients in low-risk foods revealed high intake of α-tocopherol (OR, 0.74; 95% CI, 0.56–0.99; p = 0.039) as a significant low-risk factor for liver fibrosis. This study suggests that a vegetable-based Japanese dietary pattern, through the antioxidant effects of α-tocopherol, may help prevent liver fibrosis in MASLD and the development of MASLD. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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17 pages, 300 KiB

Open AccessArticle

Efficacy of the Mediterranean Diet Containing Different Macronutrients on Non-Alcoholic Fatty Liver Disease

by Vahibe Uluçay Kestane and Murat Baş

Nutrients 2024, 16(16), 2699; https://doi.org/10.3390/nu16162699 - 14 Aug 2024

Viewed by 1063

Abstract

This study aimed to investigate the effects of the typical Mediterranean diet (TMD), low-carbohydrate Mediterranean diet (LCMD), and low-fat Mediterranean diet (LFMD) on biochemical findings, fatty liver index (FLI), anthropometric measurements, and body composition in individuals with obesity with non-alcoholic fatty liver disease [...] Read more.

This study aimed to investigate the effects of the typical Mediterranean diet (TMD), low-carbohydrate Mediterranean diet (LCMD), and low-fat Mediterranean diet (LFMD) on biochemical findings, fatty liver index (FLI), anthropometric measurements, and body composition in individuals with obesity with non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This study included 63 participants with obesity with insulin resistance diagnosed with NAFLD by ultrasonography to investigate the effects of an 8-week energy-restricted TMD, LCMD, and LFMD on biochemical findings, FLI, fibrosis-4 index (FIB-4), anthropometric measurements, and body composition. Patients were randomized into three groups and were interviewed face-to-face every week. According to the food consumption records (baseline end), the difference in the amount of sucrose and total fat consumed in the TMD group; the difference in energy intake from sucrose, monounsaturated fatty acids, and oleic acid in the LCMD group; and the difference in energy intake from fiber, sucrose, monounsaturated and polyunsaturated fatty acids, and cholesterol in the LFMD group showed significant correlations with liver enzymes and FLI (p < 0.05). In conclusion, although it has a different macronutrient composition, the Mediterranean diet may positively affect biochemical parameters and FLI in individuals with NAFLD, albeit in different ways. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

13 pages, 3258 KiB

Open AccessArticle

High-Fat Diet Delays Liver Fibrosis Recovery and Promotes Hepatocarcinogenesis in Rat Liver Cirrhosis Model

by Daisuke Taguchi, Yohei Shirakami, Hiroyasu Sakai, Toshihide Maeda, Takao Miwa, Masaya Kubota, Kenji Imai, Takashi Ibuka and Masahito Shimizu

Nutrients 2024, 16(15), 2506; https://doi.org/10.3390/nu16152506 - 1 Aug 2024

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Abstract

More effective treatments for hepatitis viral infections have led to a reduction in the incidence of liver cirrhosis. A high-fat diet can lead to chronic hepatitis and liver fibrosis, but the effects of lipid intake on liver disease status, including hepatitis C virus [...] Read more.

More effective treatments for hepatitis viral infections have led to a reduction in the incidence of liver cirrhosis. A high-fat diet can lead to chronic hepatitis and liver fibrosis, but the effects of lipid intake on liver disease status, including hepatitis C virus and alcohol, after elimination of the cause are unclear. To investigate the effects, we used a rat cirrhosis model and a high-fat diet in this study. Male Wistar rats were administered carbon tetrachloride for 5 weeks. At 12 weeks of age, one group was sacrificed. The remaining rats were divided into four groups according to whether or not they were administered carbon tetrachloride for 5 weeks, and whether they were fed a high-fat diet or control diet. At 12 weeks of age, liver fibrosis became apparent and then improved in the groups where carbon tetrachloride was discontinued, while it worsened in the groups where carbon tetrachloride was continued. Liver fibrosis was notable in both the carbon tetrachloride discontinuation and continuation groups due to the administration of a high-fat diet. In addition, liver precancerous lesions were observed in all groups, and tumor size and multiplicity were higher in the high-fat diet-fed groups. The expression of genes related to inflammation and lipogenesis were upregulated in rats fed a high-fat diet compared to their controls. The results suggest that a high-fat diet worsens liver fibrosis and promotes liver carcinogenesis, presumably through enhanced inflammation and lipogenesis, even after eliminating the underlying cause of liver cirrhosis. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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17 pages, 4494 KiB

Open AccessArticle

Ileum Proteomics Identifies Distinct Pathways Associated with Different Dietary Doses of Copper–Fructose Interactions: Implications for the Gut–Liver Axis and MASLD

by Manman Xu, Ming Li, Frederick Benz, Michael Merchant, Craig J. McClain and Ming Song

Nutrients 2024, 16(13), 2083; https://doi.org/10.3390/nu16132083 - 29 Jun 2024

Viewed by 1120

Abstract

The interactions of different dietary doses of copper with fructose contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) via the gut–liver axis. The underlying mechanisms remain elusive. The aim of this study was to identify the specific pathways leading to [...] Read more.

The interactions of different dietary doses of copper with fructose contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) via the gut–liver axis. The underlying mechanisms remain elusive. The aim of this study was to identify the specific pathways leading to gut barrier dysfunction in the ileum using a proteomics approach in a rat model. Male weanling Sprague Dawley rats were fed diets with adequate copper (CuA), marginal copper (CuM), or supplemented copper (CuS) in the absence or presence of fructose supplementation (CuAF, CuMF, and CuSF) for 4 weeks. Ileum protein was extracted and analyzed with an LC-MS. A total of 2847 differentially expressed proteins (DEPs) were identified and submitted to functional enrichment analysis. As a result, the ileum proteome and signaling pathways that were differentially altered were revealed. Of note, the CuAF is characterized by the enrichment of oxidative phosphorylation and ribosome as analyzed with the KEGG; the CuMF is characterized by an enriched arachidonic acid metabolism pathway; and focal adhesion, the regulation of the actin cytoskeleton, and tight junction were significantly enriched by the CuSF. In conclusion, our proteomics analysis identified the specific pathways in the ileum related to the different dietary doses of copper–fructose interactions, suggesting that distinct mechanisms in the gut are involved in the development of MASLD. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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13 pages, 1166 KiB

Open AccessArticle

Association between Dietary Quality and Non-Alcoholic Fatty Liver Disease in Korean Adults: A Nationwide, Population-Based Study Using the Korean Healthy Eating Index (2013–2021)

by Seong-Uk Baek, Taeyeon Kim, Yu-Min Lee, Jong-Uk Won and Jin-Ha Yoon

Nutrients 2024, 16(10), 1516; https://doi.org/10.3390/nu16101516 - 17 May 2024

Viewed by 911

Abstract

This study explored the relationship between the Korean Healthy Eating Index (KHEI) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study included 34,174 Korean adults. The KHEI was composed of three subcomponents (adequacy, moderation, and energy balance) and calculated based on a 24 [...] Read more.

This study explored the relationship between the Korean Healthy Eating Index (KHEI) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study included 34,174 Korean adults. The KHEI was composed of three subcomponents (adequacy, moderation, and energy balance) and calculated based on a 24 h dietary recall. The total score ranged from 0 to 100, with a higher score indicating a greater adherence to the Korean dietary guidelines. The total KHEI scores were categorized into quartiles (Q1–Q4). NAFLD was classified using the hepatic steatosis index. Logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The adjusted OR (95% CI) of NAFLD was 0.95 (0.87–1.03) for the Q2 group, 0.90 (0.83–0.98) for the Q3 group, and 0.79 (0.72–0.87) for the Q4 group, compared with the Q1 group. Among the subcomponents of the KHEI, individuals with high scores in the adequacy component, characterized by an abundant consumption of fruits, vegetables, and dairy products, exhibited the most pronounced association with NAFLD. A higher KHEI score was negatively associated with NAFLD in Korean adults. Therefore, the promotion of healthy dietary patterns can play a beneficial role in the prevention or management of NAFLD. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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17 pages, 4315 KiB

Open AccessArticle

5-Heptadecylresorcinol Improves Aging-Associated Hepatic Fatty Acid Oxidation Dysfunction via Regulating Adipose Sirtuin 3

by Kuiliang Zhang, Lei Jiang, Lamei Xue, Yu Wang, Yujie Sun, Mingcong Fan, Haifeng Qian, Li Wang and Yan Li

Nutrients 2024, 16(7), 978; https://doi.org/10.3390/nu16070978 - 27 Mar 2024

Cited by 1 | Viewed by 939

Abstract

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the [...] Read more.

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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18 pages, 5008 KiB

Open AccessArticle

Cholesterol Exacerbates the Pathophysiology of Non-Alcoholic Steatohepatitis by Upregulating Hypoxia-Inducible Factor 1 and Modulating Microcirculatory Dysfunction

by Evelyn Nunes Goulart da Silva Pereira, Beatriz Peres de Araujo, Karine Lino Rodrigues, Raquel Rangel Silvares, Fernanda Verdini Guimarães, Carolina Souza Machado Martins, Edgar Eduardo Ilaquita Flores, Patrícia Machado Rodrigues e Silva and Anissa Daliry

Nutrients 2023, 15(24), 5034; https://doi.org/10.3390/nu15245034 - 8 Dec 2023

Cited by 1 | Viewed by 1688

Abstract

Cholesterol is a pivotal lipotoxic molecule that contributes to the progression of Non-Alcoholic Steatohepatitis NASH). Additionally, microcirculatory changes are critical components of Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis. This study aimed to investigate the role of cholesterol as an insult that modulates microcirculatory [...] Read more.

Cholesterol is a pivotal lipotoxic molecule that contributes to the progression of Non-Alcoholic Steatohepatitis NASH). Additionally, microcirculatory changes are critical components of Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis. This study aimed to investigate the role of cholesterol as an insult that modulates microcirculatory damage in NAFLD and the underlying mechanisms. The experimental model was established in male C57BL/6 mice fed a high-fat high-carbohydrate (HFHC) diet for 39 weeks. Between weeks 31–39, 2% cholesterol was added to the HFHC diet in a subgroup of mice. Leukocyte recruitment and hepatic stellate cells (HSC) activation in microcirculation were assessed using intravital microscopy. The hepatic microvascular blood flow (HMBF) was measured using laser speckle flowmetry. High cholesterol levels exacerbated hepatomegaly, hepatic steatosis, inflammation, fibrosis, and leukocyte recruitment compared to the HFHC group. In addition, cholesterol decreased the HMBF—cholesterol-induced activation of HSC and increased HIF1A expression in the liver. Furthermore, cholesterol promoted a pro-inflammatory cytokine profile with a Th1-type immune response (IFN-γ/IL-4). These findings suggest cholesterol exacerbates NAFLD progression through microcirculatory dysfunction and HIF1A upregulation through hypoxia and inflammation. This study highlights the importance of cholesterol-induced lipotoxicity, which causes microcirculatory dysfunction associated with NAFLD pathology, thus reinforcing the potential of lipotoxicity and microcirculation as therapeutic targets for NAFLD. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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11 pages, 1059 KiB

Open AccessArticle

Effect of Intake of Extra Virgin Olive Oil on Mortality in a South Italian Cohort with and without NAFLD

by Caterina Bonfiglio, Francesco Cuccaro, Angelo Campanella, Natalia Rosso, Rossella Tatoli, Gianluigi Giannelli and Rossella Donghia

Nutrients 2023, 15(21), 4593; https://doi.org/10.3390/nu15214593 - 29 Oct 2023

Cited by 6 | Viewed by 2143

Abstract

Background: Extra-virgin olive oil (EVOO) is the main source of seasoning fat in the Mediterranean diet and it is one of the components with known protective factors on chronic-degenerative disease. We aimed to evaluate the effect of a medium-high level of oil consumption [...] Read more.

Background: Extra-virgin olive oil (EVOO) is the main source of seasoning fat in the Mediterranean diet and it is one of the components with known protective factors on chronic-degenerative disease. We aimed to evaluate the effect of a medium-high level of oil consumption on mortality in a cohort with good adherence to the Mediterranean diet. Methods: A total of 2754 subjects who had completed the food questionnaire in the Multicenter Italian study on Cholelithiasis (MICOL) cohort were included in the study. EVOO consumption was categorized in four levels (<20 g/die, 21–30 g/die, 31–40 g/die, >40 g/die). We performed a flexible parametric survival model to assess mortality by EVOO consumption level adjusted for some covariates. We also performed the analysis on subjects with and without non-alcoholic fatty liver disease (NAFLD) to evaluate the effects of oil in this more fragile sub-cohort. Results: We found a statistically significant negative effect on mortality for the whole sample when EVOO consumption was used, both as a continuous variable and when categorized. The protective effect was stronger in the sub-cohort with NAFLD, especially for the highest levels of EVOO consumption (HR = 0.58 with p < 0.05). Conclusions: Our study has shown a protective effect of EVOO consumption towards all causes of mortality. Despite the higher caloric intake, the protective power is greater for a consumption >40 g/day in both the overall cohort and the sub-cohorts with and without NAFLD. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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11 pages, 825 KiB

Open AccessArticle

Association between Dietary Niacin Intake and Nonalcoholic Fatty Liver Disease: NHANES 2003–2018

by Jie Pan, Yuhua Hu, Nengzhi Pang and Lili Yang

Nutrients 2023, 15(19), 4128; https://doi.org/10.3390/nu15194128 - 25 Sep 2023

Cited by 2 | Viewed by 3511

Abstract

Evidence regarding the association between dietary niacin intake and nonalcoholic fatty liver disease (NAFLD) is limited. The objective of this study was to examine the association of dietary niacin intake with NAFLD. Subjects aged 20 years and older who participated in the National [...] Read more.

Evidence regarding the association between dietary niacin intake and nonalcoholic fatty liver disease (NAFLD) is limited. The objective of this study was to examine the association of dietary niacin intake with NAFLD. Subjects aged 20 years and older who participated in the National Health and Nutrition Examination Survey (NHANES) 2003–2018 were included in this study. Dietary niacin intake was assessed by two 24-h dietary recalls. NAFLD was defined using the United States fatty liver index (US-FLI). Weighted logistic regression models and restricted cubic splines were used to examine the association between dietary niacin and NAFLD. Of the 12,355 participants in this study, 4378 had NAFLD. There is no evident nonlinear relationship between dietary niacin intake and the presence of NAFLD in the restricted cubic spline regression (p_overall < 0.001; p_{non-linearity} = 0.068). The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 0.84 (0.68–1.03), 0.80 (0.65–0.97), and 0.69 (0.55–0.85), respectively, when comparing the second, third, and fourth quartiles of niacin intake levels to the lowest quartile (p_trend = 0.001). Stratified analysis revealed that the effect of niacin intake on NAFLD varied in the group with or without hypertension (p_interaction = 0.033). In conclusion, our results indicate that higher dietary niacin intake may be associated with a lower likelihood of NAFLD. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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10 pages, 262 KiB

Open AccessArticle

Association of Diet Quality with Metabolic (Dysfunction) Associated Fatty Liver Disease in Veterans in Primary Care

by Natalia I. Heredia, Aaron P. Thrift, David J. Ramsey, Rohit Loomba and Hashem B. El-Serag

Nutrients 2023, 15(11), 2598; https://doi.org/10.3390/nu15112598 - 1 Jun 2023

Cited by 1 | Viewed by 1842

Abstract

Background: Diet is associated with metabolic (dysfunction)-associated fatty liver disease (MAFLD), but the dietary composition associated with MAFLD risk has not been well-examined. Aim: The purpose of this study was to assess the association of two healthy eating indices with the presence and [...] Read more.

Background: Diet is associated with metabolic (dysfunction)-associated fatty liver disease (MAFLD), but the dietary composition associated with MAFLD risk has not been well-examined. Aim: The purpose of this study was to assess the association of two healthy eating indices with the presence and severity of MAFLD in a sample of Veterans in a primary care setting. Methods: This was a single center cross-sectional study using a random stratified sample of Veterans enrolled in primary care. Participants underwent a Fibroscan and completed an interviewer-administered Diet History Questionnaire II from which we calculated the Healthy Eating Index-2015 and Alternate Mediterranean Diet Score. We used multivariable logistic regression models to assess associations of dietary quality with MAFLD. Results: We analyzed data from 187 participants, 53.5% of whom were female. On average, participants were 50.2 years of age (SD, 12.3 years) with an average BMI of 31.7 kg/m². MAFLD was detected in 78 (42%) and at least moderate fibrosis in 12 (6%) participants. We found that the Alternate Mediterranean Diet Score was inversely associated with MAFLD (adjusted OR = 0.85, 95%CI 0.72–1.00), but controlling for BMI and total energy intake attenuated the association (adjusted OR = 0.92, 95%CI 0.74–1.15). We found no statistically significant associations between the Healthy Eating Index-2015 and MAFLD or advanced fibrosis. Discussion: We found that the Alternate Mediterranean Diet Score was significantly associated with lower MAFLD risk in Veterans; however, the association was mediated by BMI and total energy intake. A Mediterranean-style diet could potentially help reduce the risk of MAFLD, particularly if it helps control total energy intake and weight. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

12 pages, 747 KiB

Open AccessArticle

Circulating Short-Chain Fatty Acids and Non-Alcoholic Fatty Liver Disease Severity in Patients with Type 2 Diabetes Mellitus

by Hui-Ju Tsai, Wei-Chun Hung, Wei-Wen Hung, Yen-Jung Lee, Yo-Chia Chen, Chun-Ying Lee, Yi-Chun Tsai and Chia-Yen Dai

Nutrients 2023, 15(7), 1712; https://doi.org/10.3390/nu15071712 - 31 Mar 2023

Cited by 9 | Viewed by 2577

Abstract

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. [...] Read more.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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17 pages, 4848 KiB

Open AccessArticle

Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice

by Nengzhi Pang, Qianrong Hu, Yujia Zhou, Ying Xiao, Wenli Li, Yijie Ding, Yunan Chen, Mingtong Ye, Lei Pei, Qiuyan Li, Yingying Gu, Yan Sun, Evandro Fei Fang, Mianrong Chen, Zhenfeng Zhang and Lili Yang

Nutrients 2023, 15(6), 1447; https://doi.org/10.3390/nu15061447 - 17 Mar 2023

Cited by 2 | Viewed by 3992

Abstract

Targeting Nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a promising anti-cancer strategy; we aimed to explore the health benefits of boosting NAD levels with nicotinamide riboside (NR) on hepatocellular carcinoma (HCC). We established three in vivo tumor models, including subcutaneous transplantation tumor [...] Read more.

Targeting Nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a promising anti-cancer strategy; we aimed to explore the health benefits of boosting NAD levels with nicotinamide riboside (NR) on hepatocellular carcinoma (HCC). We established three in vivo tumor models, including subcutaneous transplantation tumor model in both Balb/c nude mice (xenograft), C57BL/6J mice (allograft), and hematogenous metastatic neoplasm in nude mice. NR (400 mg/kg bw) was supplied daily in gavage. In-situ tumor growth or noninvasive bioluminescence were measured to evaluate the effect of NR on the HCC process. HepG2 cells were treated with transforming growth factor-β (TGF-β) in the absence/presence of NR in vitro. We found that NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice in both subcutaneous xenograft and hematogenous metastasis models. NR supplementation decreased metastasis to the bone and liver in the hematogenous metastasis model. NR supplementation also significantly decreased the size of allografted tumors and extended the survival time in C57BL/6J mice. In vitro experiments showed that NR intervention inhibited the migration and invasion of HepG2 cells triggered by TGF-β. In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of HCC progression. Full article

(This article belongs to the Special Issue Nutrition Intervention in Liver Health and Disease)

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