Lowering the dietary omega-6: omega-3 does not hinder nonalcoholic fatty-liver disease development in a murine model

Abstract

It is hypothesized that a high dietary n-6:n-3 (e.g. 10-20:1) is partly responsible for the rise in obesity and related health ailments. However, no tightly controlled studies utilizing high-fat diets (HFDs) differing in the n-6:n-3 have tested this hypothesis. The aim of the study was to determine the role the dietary n-6:n-3 plays in Non-Alcoholic Fatty-Liver Disease (NAFLD) and colitis development. We hypothesized that reducing the dietary n-6:n-3 would hinder the development of NAFLD and colitis. Male C57BL/6J mice were fed HFDs, differing in the n-6:n-3 (1:1, 5:1, 10:1, 20:1), for 20 weeks. GC/MS was used to analyze the hepatic phospholipid arachidonic acid:eicosapentaenoic acid (AA:EPA) and AA:docosahexaenoic acid (AA:DHA). Hepatic metabolism, inflammatory signaling, macrophage polarization, gene expression of inflammatory mediators, oxidative and ER stress, and oxidative capacity were assessed as well as colonic inflammatory signaling, and gene expression of inflammatory mediators, and tight-junction proteins. Although reducing the dietary n-6:n-3 lowered the hepatic phospholipid AA:EPA and AA:DHA in a dose-dependent manner and mildly influenced inflammatory signaling, it did not significantly attenuate NAFLD development. Further, the onset of NAFLD was not paired to colitis development nor changes in tight-junction protein gene expression. In conclusion, reducing the dietary n-6:n-3 did not attenuate NAFLD progression nor is it likely that colitis, or gut permeability, play a role in NAFLD initiation in this model.

A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

“…Additionally, both HFDs increased hepatic PPARγ gene expression compared to the AIN-76A control diet. This increase in hepatic PPARγ resulting from HFD consumption is consistent with our previous findings [23] and those of others, and further supports the important role of PPARγ in NAFLD development [38]. Interestingly, the mRNA expression of ACAC1 and SREBP-1, two genes known to play integral roles in hepatic fatty acid metabolism, were found to be unchanged with HFD consumption.…”

“…Hematoxylin and eosin staining of epididymal AT and Liver were performed as previously described [23]. Immunohistochemistry for adipose tissue F4/80 (AbD-Serotec) was performed as described by the manufacturer's instructions.…”

High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer

“…Hematoxylin and eosin staining of epididymal adipose tissue and colons were performed as previously described (14). Immunohistochemistry for adipose tissue F4/80 (AbD-Serotec) was performed as described by the manufacturer's instructions.…”

“…Membranes were stained with a Ponceau S solution to verify equal protein loading and transfer efficiency. Western blots were performed as previously described using the primary antibody, Muc2 ( (14). ␤-Actin and ␣-tubulin were used for loading controls depending on the molecular weight of the target antibody.…”

Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model

“…Quanitification of primary tumor mRNA gene expression was performed for macrophage markers (CD64 and Mertk) and cytokines (IL-6, TNFa, and IL1b) (Applied Biosystems, Foster City, CA) as described previously. 24 RNA quality and concentration was analyzed using a NanoPhotometer Pearl (Implen). Murine 18s rRNA was used as the housekeeping gene to normalize all of the data obtained.…”