A diet high in alpha linolenic acid and monounsaturated fatty acids attenuates hepaticsteatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats

This study investigated the efficacy of the plant based n3 fatty acid, alpha linolenic acid (ALA),a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55 percent energy) diets containing high oleic canola oil, canola oil, a canola/ flax oil blend (C/F,3 to1), safflower oil, soybean oil, or lard.  After 12 weeks, C/F and weight matched (WM) groups had 20 percent less liver lipid.  Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation  and elongation did not account for this effect. The C/F group had the highest total n3 and EPA in hepatic phospholipids (PL),as well as one of the highest DHA and lowest arachidonic acid (n6) concentrations.  In conclusion, the C/F diet with the highest  content of the plant-based n3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. (Authors abstract)

Obesity does not occur in isolation in the body, but is typically accompanied by insulin resistance, hyper lipidemia and hypertension, which are all components of the metabolic syndrome. It has also been suggested that inflammation  and non alcoholic fatty liver disease (NAFLD) be added to the definition of the metabolic syndrome as they are closely related to all of the classical components of the metabolic syndrome. N3 fatty acids, and in particular fish oils, have been proposed to prevent hepaticsteatosis and, thus, slow the progression to NAFLD by increasing hepatic fatty acid oxidation, possibly via peroxisome proliferator activated receptor α (PPAR-alpha) activation, and by decreasing hepatic fatty acid synthesis through sterol regulatory element binding protein 1c (SREBP 1c).  Previous research has primarily examined the effects of dietary fatty acids on obesity and related conditions such as insulin resistance in the context of SFAs, PUFAs and very long chain n3 PUFAs found in marine sources. Currently, there is limited research on the effects of MUFAs and ALA on the metabolic syndrome and related conditions, even though in North America there is wide spread consumption of canola oil,which contains high amounts of MUFA and ALA.  The overall objective of this research study was to investigate the effects of dietary oils ,including those that are rich in ALA and MUFA on hepatic steatosis and hepatic fatty acid composition as well as metabolic syndrome parameters in a diet induced obesity (DIO) rat model. The DIO rodent model more closely mimics the phenotype and pathogenesis of human obesity than genetic and pharmacologically induced  models of obesity.

The main finding of this study was that the C/F diet attenuated hepatic steatosis,and altered the hepatic PL fatty acid profile by increasing  EPA and DHA.  The levels of EPA or  DHA in liver were not related to the mRNA levels of desaturation(Fads1,Fads2,Scd1)and elongation (Elovl2, Elovl5) enzymes. All  the canola oil groups (HOC,C and C/F) gained the least amount of weight during the study and had the  lowest final bodyweight, although adiposity was unaffected as assessed by visceral fat mass.

.The positive effect of the C/F diet in attenuating hepatic lipid accumulation maybe linked to the significantly  higher dietary intake of ALA (2 fold relative to C and SB, and 410 fold vs the remaining diets).No other parameter was unique to the C/F diet, including the accumulation of EPA and DHA in the hepatic lipids.  Additionally, because the Land WM groups consumed the same lard diet, the less hepatic fat accumulation in the WM group is likely due to their restricted calorie intake and thus  lower  body weight.It is well known that a reduction in calories can quickly reduce the amount of fat stored in the liver. The data suggest that dietary fats and oils differ in their ability to attenuate hepatic lipid accumulation and serum TAG concentrations, and that hepatic lipid and serum TAG concentrations are not as strongly related as once believed.  Additionally, no differences were seen among groups in terms of fasting serum free fatty acids or cholesterol. Although all groups except the C/F and WM groups developed hepatic steatosis and the HOC group had the highest liver weight as a percent body weight, the HOC,C, C/F and SF groups had the lowest fasting serum glucose concentrations, and the HOC and SF had among the lowest HOMA score.

The hepatic fatty acid composition of hepatic TAG mimicked the diet fatty acid composition.  Supplemental ALA or EPA have little effect on DHA levels in  blood or breast milk, and dietary supplements with preformed DHA are required to increase blood DHA levels.  Interestingly, the C/F, SFand SB groups had the highest LA in hepatic PL.  In the present study, the RNA levels of Scd1 were similar among groups even though the C/F and WM groups had the lowest percent liver lipids and the SB and SF diets had the highest dietary PUFAs, whereas the Land WM diets had the highest dietary SFA.  The C/F group had among the lowest percent liver lipids, the highest EPA and among the highest DHA in the liver but interestingly had similar levels of Scd1 and Elovl5 as the other dietary treatment groups and among the highest mRNA levels of Fads1, Fads2 and Elovl2. Thus, in all cases, in the current study, the mRNA levels of desaturase and elongase enzymes do not seem to be related to the degree of hepatic steatosis or the proportion of EPA or DHA in the liver lipids. For the three canola oil diets,there was a relatively direct relationship between the amount of ALA present in the diet and the concentration of ALA and EPA present in hepatic TAG.  It therefore appears that the availability of fatty acids substrates is a better indicator of conversion capability compared to mRNA levels of genes required for elongation and desaturation. In summary, the C/F diet containing MUFA and the highest amount of ALA was beneficial for reducing hepatic steatosis in DIO rats. Despite concerns about low conversion rates, dietary ALA was effective for elevating EPA and maintaining one of the highest DHA concentrations in hepatic PL. Although the present study employed a high fat diet to induce obesity and investigate the effects of dietary fat composition during development of hepatic steatosis, the results warrant further investigation of MUFA and ALA interventions in other models of NAFLD and translational studies to humans. (Editors comments)