Dietary omega-3 and omega-6 polyunsaturated fatty acids modulate hepatic pathology

Abstract

Recent evidence has suggested that dietary polyunsaturated fatty acids (PUFAs) modulate inflammation; however, few studies have focused on the pathobiology of PUFA using isocaloric and isolipidic diets and it is unclear if the associated pathologies are due to dietary PUFA composition, lipid metabolism or obesity, as most studies compare diets fed ad libitum. Our studies used isocaloric and isolipidic liquid diets (35% of calories from fat), with differing compositions of omega (ω)-6 or long chain (Lc) ω-3 PUFA that were pair-fed and assessed hepatic pathology, inflammation and lipid metabolism. Consistent with an isocaloric, pair-fed model we observed no significant difference in diet consumption between the groups. In contrast, the body and liver weight, total lipid level and abdominal fat deposits were significantly higher in mice fed an ω-6 diet. An analysis of the fatty acid profile in plasma and liver showed that mice on the ω-6 diet had significantly more arachidonic acid (AA) in the plasma and liver, whereas, in these mice ω-3 fatty acids such as eicosapentaenoic acid (EPA) were not detected and docosahexaenoic acid (DHA) was significantly lower. Histopathologic analyses documented that mice on the ω-6 diet had a significant increase in macrovesicular steatosis, extramedullary myelopoiesis (EMM), apoptotic hepatocytes and decreased glycogen storage in lobular hepatocytes, and hepatocyte proliferation relative to mice fed the Lc ω-3 diet. Together, these results support PUFA dietary regulation of hepatic pathology and inflammation with implications for enteral feeding regulation of steatosis and other hepatic lesions.

Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet‐Induced Accumulation of Lipid in the Liver of ApoE−/− Mice

“…The contents of DHA and EPA in the serum and liver tissue of DHA/EPA-treated mice were notably increased in our study. It is also well known that dietary fat, including DHA and EPA, alters the FA composition of various organs [ 12 , 18 ]. Our results showed that the increased MUFAs and decreased SFAs, n-6 PUFAs, and n-3 PUFAs with an increase of the n-6/n-3 ratio were observed in liver tissue of HFD-fed mice compared to that in the ND-fed mice.…”

“…Recently, the effects of different dietary n-6/n-3 ratio on health and disease have drawn close attention. A higher intake of n-6 FA and higher dietary n-6/n-3 FA ratio were reported in NAFLD subjects [ 18 ]. On the other hand, additional evidence also highlighted the role of ratios of DHA and EPA in the prevention and treatment of chronic disease in rat models [ 19 – 22 ], indicating the importance of both n-6/n-3 ratios and DHA/EPA ratios.…”

“…On the other hand, additional evidence also highlighted the role of ratios of DHA and EPA in the prevention and treatment of chronic disease in rat models [ 19 – 22 ], indicating the importance of both n-6/n-3 ratios and DHA/EPA ratios. It has been known that the intake of dietary fat alters the FA composition of plasma and various organs, including the liver [ 12 , 18 ]. Lipidomics analysis has also revealed the role of different EPA/DHA ratios in the modulation of inflammation and oxidative markers in genetically obese hypertensive rats through the downregulation of the production of proinflammatory n-6 eicosanoids [ 23 ].…”

Mechanisms of Parenteral Nutrition–Associated Liver and Gut Injury

“…It has been shown that high levels of PUFAs and a high ω‐6/ω‐3 ratio in PN may contribute to increased incidence of cholestasis, steatosis, sepsis, changes in neutrophil function, and upregulation of matrix metalloproteinases (MMPs) . The ω‐6 PUFA arachidonic acid (AA) produces prostaglandins (PGs), thromboxanes (TXs), 5‐hydroxy‐eicosatetraenoic acid, and other 4‐series leukotrienes (LTs) that are proinflammatory . The ω‐3 fatty acid eicosapentaenoic acid (EPA) produces 3‐series PGs, TXs, and 5‐series LTs, which have less detrimental effect than AA‐derived mediators have …”

Flavonoids as putative modulators of Δ4‐, Δ5‐, and Δ6‐desaturases: Studies in cultured hepatocytes, myocytes, and adipocytes

“…The liver is an important organ for PUFA synthesis . It also benefits from omega‐3 PUFAs by decreased incidence of nonalcoholic fatty liver disease, less apoptotic hepatocytes, increased glycogen storage, and lower hepatic triacylglycerol secretion . High CER levels on the other hand may favor the development of nonalcoholic fatty liver disease, apoptosis, and lipogenesis in liver .…”