Dietary protein insufficiency: an important consideration in fatty liver disease?

Ampong, Isaac; Watkins, Adam; Gutierrez-Merino, Jorge; Ikwuobe, John; Griffiths, Helen R.

doi:10.1017/s0007114519003064

Cited by 40 publications

(30 citation statements)

References 82 publications

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“…We established a model for RAS immunization under a low protein diet and a subsequent challenge under protein-sufficient conditions that alters the nutritional status of the host, without affecting parasite development. We showed that our newly-established protocol successfully accomplished the proposed objectives, since: i) mice under LP diet gained less weight and consumed more water than their counterparts receiving AP diet, in line with previous reports involving reduced dietary protein ( 22 , 23 , 42 ); ii) the livers of mice under LP diet showed increased expression of lipogenesis-related genes, in agreement with the association of low dietary protein with hepatic lipid accumulation and increased risk of fatty liver disease ( 43 , 44 ); iii) following challenge, Pb liver load and blood parasitemia were equivalent in non-immunized mice maintained under LP or AP diet.…”

Section: Discussionsupporting

confidence: 80%

Impact of Dietary Protein Restriction on the Immunogenicity and Efficacy of Whole-Sporozoite Malaria Vaccination

et al. 2022

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Malaria remains one of the world’s most prevalent infectious diseases. Several vaccination strategies currently under investigation aim at hampering the development of the Plasmodium parasite during the clinically silent liver stage of its life cycle in the mammalian host, preventing the subsequent disease-associated blood stage of infection. Immunization with radiation-attenuated sporozoites (RAS), the liver-infecting parasite forms, can induce sterile protection against malaria. However, the efficacy of vaccine candidates in malaria-naïve individuals in high-income countries is frequently higher than that found in populations where malaria is endemic. Malnutrition has been associated with immune dysfunction and with a delay or impairment of the immune response to some vaccines. Since vaccine efficacy depends on the generation of competent immune responses, and malaria-endemic regions are often associated with malnutrition, we hypothesized that an inadequate host nutritional status, specifically resulting from a reduction in dietary protein, could impact on the establishment of an efficient anti-malarial immune response. We developed a model of RAS immunization under low protein diet to investigate the impact of a reduced host protein intake on the immunogenicity and protective efficacy of this vaccine. Our analysis of the circulating and tissue-associated immune compartments revealed that a reduction in dietary protein intake during immunization resulted in a decrease in the frequency of circulating CD4+ T cells and of hepatic NK cells. Nevertheless, the profile of CD8+ T cells in the blood, liver and spleen was robust and minimally affected by the dietary protein content during RAS immunization, as assessed by supervised and in-depth unsupervised X-shift clustering analysis. Although mice immunized under low protein diet presented higher parasite liver load upon challenge than those immunized under adequate protein intake, the two groups displayed similar levels of protection from disease. Overall, our data indicate that dietary protein reduction may have minimal impact on the immunogenicity and efficacy of RAS-based malaria vaccination. Importantly, this experimental model can be extended to assess the impact of other nutrient imbalances and immunization strategies, towards the refinement of future translational interventions that improve vaccine efficacy in malnourished individuals.

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Section: Discussionsupporting

confidence: 80%

Impact of Dietary Protein Restriction on the Immunogenicity and Efficacy of Whole-Sporozoite Malaria Vaccination

et al. 2022

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“…Another potential source of OCSFA is from the action of peroxisomal 2-OH acyl CoA lyase that cleaves and removes one carbon during fatty acid α-oxidation ( Ampong et al, 2020 ). Liver expression of this gene was lower in HFD compared to CD-fed animals and may contribute to lower C17:0 and other have shown that 2-OH acyl CoA lyase is a major contributor to determining C17:0 levels.…”

Section: Discussionmentioning

confidence: 99%

Odd chain fatty acid metabolism in mice after a high fat diet

Ampong

Ikwuobe

Brown

et al. 2022

The International Journal of Biochemistry & Cell Biology

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Epidemiological studies show that higher circulating levels of odd chain saturated fatty acids (FA: C15:0 and C17:0) are associated with lower risk of metabolic disease. These odd chain saturated fatty acids (OCSFA) are produced by α-oxidation in peroxisomes, de novo lipogenesis, from the diet and by gut microbiota. Although present at low concentrations, they are of interest as potential targets to reduce metabolic disease risk. To determine whether OCSFA are affected by obesogenic diets, we have investigated whether high dietary fat intake affects the frequency of OCSFA-producing gut microbiota, liver lipid metabolism genes and circulating OCSFA. FA concentrations were determined in liver and serum from pathogen-free SPF C57BL/6 J mice fed either standard chow or a high fat diet (HFD; 60% calories as fat) for four and twelve weeks. Post-mortem mouse livers were analysed histologically for fat deposition by gas chromatography–mass spectrometry for FA composition and by qPCR for the lipid metabolic genes fatty acid desaturase 2 ( FADS2 ), stearoyl CoA desaturase 1 ( SCD1 ), elongation of long-chain fatty acids family member 6 ( ELOVL6 ) and 2-hydroxyacyl-CoA lyase 1 ( HACL ). Gut microbiota in faecal pellets from the ileum were analysed by 16S RNA sequencing. A significant depletion of serum and liver C15:0 (>50%; P < 0.05) and liver C17:0 (>35%; P < 0.05) was observed in HFD-fed SPF mice in parallel with hepatic fat accumulation after four weeks. In addition, liver gene expression ( HACL1, ELOVL6, SCD1 and FADS2 ) was lower (>50%; P < 0.05) and the relative abundance of beneficial C3:0-producing gut bacteria such as Akkermansia , Lactobacillus , Bifidobacterium was lower after HFD in SPF mice. In summary, high dietary fat intake reduces serum and liver OCSFA, OCSFA-producing gut microbiota and is associated with impaired liver lipid metabolism. Further studies are required to identify whether there is any beneficial effect of OCSFA and C3:0-producing gut bacteria to counter metabolic disease.

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“…Dietary protein deficiency has been associated with excessive TG storage and NAFLD in population studies, and older adults are at risk for protein malnutrition [ 32 ]. Therefore, in addition to common pathogenic risks of NAFLD, we also included nutritional risk as a variable in our analysis of the association between FSH and NAFLD.…”

Section: Discussionmentioning

confidence: 99%

A low follicle-stimulating hormone level is a protective factor for non-alcoholic fatty liver disease in older men aged over 80

Zhu

Zhang

et al. 2021

BMC Geriatr

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Purpose Recent studies have suggested the significant relationship between follicle-stimulating hormone (FSH) and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. However, it is unknown whether FSH impacts the risk of NAFLD in men. This study aimed to investigate the association between serum FSH levels and NAFLD in elderly Chinese men aged 80–98, a particular group with worse outcomes of NAFLD. Patients and methods A cross-sectional analysis was performed in 444 subjects in a geriatric health center. The highest quartile of serum FSH was used as reference. Hepatic steatosis was defined according to the results of liver ultrasound. Fibrosis-4 (FIB-4) Index > 2.67 was defined as advanced fibrosis. Results Based on liver ultrasound, 108 (24.3%) subjects had NAFLD. FSH level were negatively correlated with total testosterone, estradiol, nutritional risk, and the prevalence of high education level (all P < 0.01), and positively correlated with age, luteinizing hormone, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The correlation between FSH and body mass index or antihypertensive drug usage was marginally significant (P = 0.057; P = 0.066, respectively). The percentage of subjects with NAFLD had a trend to increase following the quartiles of serum FSH (20.0% in quartile 1, 18.2% in quartile 2, 27.3% in quartile 3, and 31.6% in quartile 4). After adjustment for common pathogenic risk factors, nutritional risk, and other sex hormones, serum FSH were progressively associated with odds ratios for NAFLD. The adjusted odds ratios and 95% CIs for quartile 1, quartile 2, and quartile 3, compared with quartile 4 were 0.132 (0.034–0.516), 0.190 (0.052–0.702), and 0.404 (0.139–1.173), respectively. Obesity was not involved in the potential negative role of circulating FSH on the risk of NAFLD in our population. Furthermore, our results revealed no significant association between FSH and advance fibrosis, the OR (95% CI) for advanced fibrosis was 1.018 (0.983–1.054) (P = 0.316) after adjusting for the potential covariates, although a positive correlation of FSH and FIB-4 score was observed (r = 0.325, P = 0.001). Conclusion Low FSH level may decrease the risk of NAFLD in elderly Chinese men. These findings warrant replication in more extensive studies.

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Dietary protein insufficiency: an important consideration in fatty liver disease?

Cited by 40 publications

References 82 publications

Impact of Dietary Protein Restriction on the Immunogenicity and Efficacy of Whole-Sporozoite Malaria Vaccination

Impact of Dietary Protein Restriction on the Immunogenicity and Efficacy of Whole-Sporozoite Malaria Vaccination

Odd chain fatty acid metabolism in mice after a high fat diet

A low follicle-stimulating hormone level is a protective factor for non-alcoholic fatty liver disease in older men aged over 80

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