Effect of Dietary Alpha‐Linolenic Acid and Long‐Chain n‐3 Polyunsaturated Fatty Acids on Fructose‐Induced Hypertriglyceridemia, Hepatic Oxidative Stress and Inflammation
Authors: Sakamuri Anil , Jeyapal Sugeedha , Kona Suryam Reddy , Pothana Sailaja , Ibrahim Ahamed 
Published: June 2021

Impact of dietary n‐6/n‐3 polyunsaturated fatty acids (PUFA) ratio on the fructose‐induced hypertriglyceridemia, hepatic oxidative stress and inflammation was not explored previously. Here, we report the effect of diets containing n‐6 PUFA & α‐linolenic acid (ALA, 18:3 n‐3 PUFA) and n‐6 PUFA & long chain n‐3 PUFA (docosahexanoic acid and eicosapentaenoic acid, DHA and EPA) in the ratio of 2:1 and 5:1 respectively on fructose‐induced hypertriglyceridemia and hepatic oxidative stress and inflammation in the rats.

Weanling Wistar rats were divided in to four groups and fed with diets containing starch (n‐6/n‐3 PUFA ratio 215:1), fructose (n‐6/n‐3 PUFA ratio 215:1) and fructose‐with n‐6/n‐3 PUFA ratio 2:1 (18:3 n‐3 PUFA) and 5:1 (long chain n‐3 PUFA) diets for twenty‐four weeks. Circulatory triglycerides were measured along with the hepatic triglyceride content. Gene expression of proteins belong to pro‐ and anti‐inflammatory cytokines, oxidative and endoplasmic stress along with pre‐receptor metabolism of glucocorticoids were quantified by quantitative PCR. Hepatic glutathione peroxidase and catalase activities were measured along with lipid peroxidation.

Decreasing dietary n‐6/n‐3 PUFA ratio by supplementing ALA and LC n‐3 PUFA significantly reduced the fructose‐induced hypertriglyceridemia by 42% and 47% respectively (p≤0.05) without altering the hepatic weight and triglyceride content. ALA and long chain (LC) n‐3 PUFA feeding significantly reduced the fructose‐induced increase in lipogenic gene expression including stearoyl‐CoA desaturase, acetyl‐CoA carboxylase 1, carbohydrate‐responsive element‐binding protein, peroxisome proliferator‐activated receptor ‐ gamma, liver X receptor alpha, sterol regulatory element‐binding transcription factor 1, but only LC n‐3 PUFA feeding reduced the peroxisome proliferator‐activated receptor ‐ alpha, transcription factor regulating beta‐oxidation genes. ALA and LC n‐3 PUFA also reduced hepatic expression of 11betab‐hydroxysteroid dehydrogenase 1, an active glucocorticoid generating enzyme along with p47phox and glucose‐regulated protein 78 genes related to oxidative and ER stress respectively. Interestingly only, LC n‐3 PUFA‐feeding decreased the fructose‐induced expression of inflammatory genes including monocyte chemoattractant protein 1, tumor necrosis factor‐alpha and toll‐like receptor 4. Both ALA and LC n‐3 PUFA corrected the fructose‐induced reduction in glutathione peroxidase and catalase activity. ALA and n‐3 PUFA reduced the elevated lipid peroxidation significantly by 14% and 28% (p≤0.05).

We conclude that replacement of dietary n‐6 PUFA with ALA and LC n‐3 PUFA ameliorates fructose‐induced hypertriglyceridemia and hepatic lipogenic gene expression. We also conclude that LC n‐3 PUFA is more protective when compared to ALA from fructose‐induced hepatic lipid peroxidation and only dietary LC n‐3 PUFA reduced fructose‐induced hepatic inflammatory genes. Though both ALA and LC n‐3 PUFA reduced fructose‐induced hypertriglyceridemia, considering protective effects of LC n‐3 PUFA on hepatic oxidative stress and inflammation, and as LC n‐3 PUFA exhibited protective nature at less quantity than ALA, we propose that diets with LC n‐3 PUFA gives better protection against fructose‐induced hepatic oxidative stress and inflammation.

Support or Funding Information

The present study was carried out with the financial support of Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India, and Indian Council of Medical Research (ICMR), Government of India. AS was supported by Council of Scientific and Industrial Research (CSIR).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.