Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study

Hodson, Leanne; Bhatia, Lokpal; Scorletti, Eleonora; Smith, Debbie E.; Jackson, Nicola; Shojaee‐Moradie, Fariba; Umpleby, Margot; Calder, Philip C.; Byrne, Christopher D.

doi:10.1038/ejcn.2017.9

Cited by 56 publications

(60 citation statements)

References 35 publications

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“…The percentage of ω-3 poly-unsaturated FAs (PUFAs) in hepatic triglycerides (TG) and plasma decreased significantly, but that of saturated FAs increased in NASH patients (6,7). Several clinical investigations and a meta-analysis on patients with nonalcoholic fatty liver diseases (NAFLDs) demonstrated a beneficial effect of ω-3 PUFA (8)(9)(10). In contrast, controlled trials of NASH patients did not show any improvement in histological features after treatment with either ω-3 fish oil or PUFA (11,12).…”

Section: Introductionmentioning

confidence: 99%

A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis

Han

Shin

Kim

et al. 2019

Journal of Clinical Investigation

121

102

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Figure 6. RORα activates Alox12-dependent MaR1 synthesis. (A) Seven-week-old C57BL/6 mice were fed with either LFD or HFD for 12 weeks (n = 4) or fed with MCS or MCD for 4 weeks (n = 5) (first and second panels). The LFD-fed C57BL/6 mice were treated with 5 mg/kg BW SR1078 for 5 days (n = 5) (third panel). Seven-week-old LFD-fed floxed and RORα-MKO mice were sacrificed (n = 11) (fourth panel). (B) Liver samples were obtained from the floxed and RORα-MKO mice those described in Supplemental Figure 1 (n = 5). Levels of MaR1 and RvD1 in liver tissues were measured. *P < 0.05 and **P < 0.01; ## P < 0.01 for A and B. (C) DHA-treated peritoneal macrophages (PM) and Raw 264.7 cells were treated with 5 μM SR1078 for 24 hours, or the cells were infected by lenti-shGFP or lenti-shRORα for 48 hours. Intracellular amount of MaR1 were measured. *P < 0.05 (n = 3). (D) A scheme for biosynthesis of MaR1 by LOX family. (E) Expression levels of 12-LOX protein (Alox12 mRNA) and 12/15-LOX protein (Alox15 mRNA) in liver macrophages (LM), PM, Raw 264.7, bone marrow-derived macrophages (BMDM), and hepatocytes were measured by Western blotting and qRT-PCR. (F) mRNA levels of Alox genes in the isolated LMs from floxed and RORα-MKO mice as shown in A were measured by qRT-PCR. (G) LMs were treated with SR1078 or MaR1 (left). LMs were infected by AAV-GFP/AAV-RORα or lenti-shGFP/lenti-shRORα as indicated (right). The mRNA levels of Alox12 were measured by qRT-PCR. *P < 0.05 (n = 3) for F and G. (H) Schematic representation of the mouse Alox12 promoter with the putative ROREs shown as red boxes (top). Raw 264.7 cells were transfected with the deleted Alox12 promoter-Luc reporter with empty vector (EV) or Myc-RORα. Luciferase activity was measured and normalized by β-galactosidase activity. *P < 0.05 (n = 3) (middle). Raw 264.7 cells were transfected with Myc-RORα, or cells were treated with SR1078 or MaR1. DNA fragments that contain flanking region of the ROREs on the Alox12 promoter were immunoprecipitated with indicated antibodies and then amplified by PCR (bottom). (I) DHA-treated PMs were treated with 5 μM SR1078, 5 μM baicalein, or 10 μM NCTT-956. Intracellular MaR1 content was measured. (J) LMs were treated with baicalein, or NCTT-956 in the presence or absence of DHA. The mRNA levels of Rora were measured by qRT-PCR (left). The CD206 + /CD80 + ratio of F4/80 + cells was determined by flow cytometry (right). *P < 0.05 and # P < 0.05 (n = 3) for I and J. The data represent mean ± SD. Data were analyzed by Mann-Whitney U test for simple comparisons or Kruskal-Wallis test for multiple groups.

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Section: Introductionmentioning

confidence: 99%

A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis

Han

Shin

Kim

et al. 2019

Journal of Clinical Investigation

121

102

View full text Add to dashboard Cite

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“…A study had been carried out in NAFLD patients treated with omega 3 poly unsaturated fatty acids to assess the changes in erythrocyte docosahexaenoic acid enrichment, a surrogate marker for tissue enrichment {Hodson L, et al, 2017. 78 }.They found out that individuals who showed docosahexaenoic acid enrichment >2% have changes in hepatic fatty acid metabolism and insulin sensitivity which leads to the reduction of hepatic fat content.…”

Section: G Study Reports Related To Treatment Of Nafldmentioning

confidence: 99%

A Recent Research on Non Alcoholic Fatty Liver Disease

2019

IJRTE

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Non alcoholic fatty liver disease (NAFLD) is a persistent condition of liver steatosis in the absence of alcohol consumption. The main risk factors associated with the disease are hypertension, diabetes mellitus and dyslipidemia these are together termed as metabolic syndrome. Recent studies identified that children are more vulnerable to develop NAFLD in future due to sedentary life styles and poor diet. NAFLD can further make complications of cardiovascular and liver related disorders. Apart from these causes there are factors such as enzyme, gene expression; amino acid regulation and so on in the human body plays an important role in the development of NAFLD. The objective of this research is to summaries the various ways by which a NAFLD is affected in a normal individual and to point out current research on treatment strategy for the NAFLD.

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“…Taken together it has been found that diets overfeeding SFA increase liver fat content to a greater extent than diets overfeeding unsaturated (primarily monounsaturated and n-6 PUFA) fatty acids (45)(46)(47) . Supplementing the diet with n-3 fatty acids (namely EPA and DHA) at 4 g/d (as ethyl esters) for periods between 8 weeks and 16 months has also been reported to decrease liver fat (48)(49)(50) .…”

Section: Fatty Acid Sources: Dietarymentioning

confidence: 99%

“…We have undertaken a pilot study to investigate the effect of EPA and DHA supplementation on hepatic fatty acid partitioning (50) . We found that long-term (16-18 months) supplementation with EPA and DHA (total 4 g/d as ethyl esters) significantly decreased the contribution of DNL fatty acids to VLDL-TAG in the postprandial state, in individuals who showed an increase of >2 % in erythrocyte DHA compared with those who did not (50) . In the individuals with an increased erythrocyte DHA, we found a significantly higher incorporation of 13 C (which was given in a test meal) appear in plasma 3-OHB over the postprandial period, suggesting that a greater proportion of recently ingested fatty acids were undergoing oxidation to produce 3-OHB (50) .…”

Section: Fatty Acid Sources: Dietarymentioning

confidence: 99%

Hepatic fatty acid synthesis and partitioning: the effect of metabolic and nutritional state

Hodson

2018

Proc. Nutr. Soc.

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When we consume dietary fat, a series of complex metabolic processes ensures that fatty acids are absorbed, transported around the body and used/stored appropriately. The liver is a central metabolic organ within the human body and has a major role in regulating fat and carbohydrate metabolism. Studying hepatic metabolism in human subjects is challenging; the use of stable isotope tracers and measurement of particles or molecules secreted by the liver such as VLDL-TAG and 3-hydroxybutyrate offers the best insight into postprandial hepatic fatty acid metabolism in human subjects. Diet derived fatty acids are taken up by the liver and mix with fatty acids coming from the lipolysis of adipose tissue, and those already present in the liver (cytosolic TAG) and fatty acids synthesised de novo within the liver from non-lipid precursors (known as de novo lipogenesis). Fatty acids are removed from the liver by secretion as VLDL-TAG and oxidation. Perturbations in these processes have the potential to impact on metabolic health. Whether fatty acids are partitioned towards oxidation or esterification pathways appears to be dependent on a number of metabolic factors; not least ambient insulin concentrations. Moreover, along with the phenotype and lifestyle factors (e.g. habitual diet) of an individual, it is becoming apparent that the composition of the diet (macronutrient and fatty acid composition) may play pivotal roles in determining if intra-hepatic fat accumulates, although what remains to be elucidated is the influence these nutrients have on intra-hepatic fatty acid synthesis and partitioning. Liver: VLDL-TAG: Fatty acid partitioning: Fatty acid oxidationThe liver has a major role in regulating metabolic homeostasis; it is a central cross-road for fatty acid and glucose metabolism. It serves as an intermediary organ between dietary (exogenous) and endogenous energy sources and other extra-hepatic organs/tissues that consume energy; perturbations in its metabolism have the potential to impact widely on metabolic disease risk. In health, the liver rapidly adapts to alterations in nutritional state and the nutrient fluxes that occur from a fasted (postabsorptive) to fed (postprandial) state. However, the deposition of fat (ectopic fat) in nonadipose tissues such as the liver has been suggested to be an important factor in the development of obesity related metabolic abnormalities (1,2) . The net retention of intra-hepatic fat is a prerequisite for the development of non-alcoholic fatty liver disease (NAFLD) (3) , which is now recognised as the hepatic manifestation of the metabolic syndrome (2) . A well-recognised risk factor for NAFLD is obesity, and both are risk factors for more severe metabolic diseases such as type-2 diabetes and CVD; the prevalence of NAFLD parallels that of type-2 diabetes (4) . Why the liver starts to accumulate fat is not well understood but is likely to occur when fatty acid input and synthesis exceed the liver's capacity for removal (e.g. for secretion or oxidation) (5)(6)(7) . The intra-hepa...

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Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study

Cited by 56 publications

References 35 publications

A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis

A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis

A Recent Research on Non Alcoholic Fatty Liver Disease

Hepatic fatty acid synthesis and partitioning: the effect of metabolic and nutritional state

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