Manifestations of Fasting-Induced Fatty Liver and Rapid Recovery from Steatosis in Voles Fed Lard or Flaxseed Oil Lipids
Manifestations of Fasting-Induced Fatty Liver and Rapid Recovery from Steatosis in Voles Fed Lard or Flaxseed Oil Lipids
Year: 2013
Authors: Mustonen, A-M. Karja, V. Kilpio, M. Tammi, R. Tammi, M. Rouvinen-Watt, K. Halonen, T. Nieminen, P.
Publication Name: Nutrients
Publication Details: Volume 5; Number 10; Pages 4211-4230
Abstract:
Long-chain n3 polyunsaturated fatty acids (PUFA) can have beneficial effects against fat deposition, cardiovascular diseases, and liver steatosis. We investigated how diets based on lard (predominantly saturated and monounsaturated fatty acids) or flaxseed oil (rich in 18:3n3) affect liver fat-percent and fatty acid profiles of tundra voles (Microtus oeconomus). We also studied potential participation of hyaluronan (HA) in the pathology of fatty liver and whether the development and recovery of fasting-induced steatosis are influenced by n3 PUFA. The dietary fatty acid composition was manifested in the liver fatty acid signatures. Fasting for 18 h induced macrovesicular steatosis and the liver fat-percent increased to 22percent independent of the preceding diet. Fasting-induced steatosis did not involve inflammation or connective tissue activation indicated by the absence of both leukocyte accumulation and increased HA. Food deprivation modified the liver fatty acid signatures to resemble more closely the diets. Fasting reduced the proportions of long-chain n3 PUFA in both dietary regimes and n3/n6 PUFA ratios in the lard-fed voles. Decreases in long-chain n3 PUFA may promote lipid accumulation by modulating the expression of lipid-metabolizing genes. Dietary 18:3n3 did not prevent the development or attenuate the manifestation of steatosis in the fasted voles or promote the recovery. (Authors abstract)
Non-alcoholic fatty liver disease (NAFLD) is a major health burden in Western countries, affecting 20percent–30percent of the general population. While NAFLD is frequently asymptomatic and relatively benign, it can develop into non-alcoholic steatohepatitis (NASH), which has the potential to progress to cirrhosis and hepatocarcinoma. NAFLD is closely associated with features of the metabolic syndrome, such as obesity, insulin resistance, hyperlipidemia, and hypertension. NAFLD is characterized by a depletion of long chain (LC) n3 and n6 PUFA (ARA, EPA, and 22:6n3 [DHA]) from the liver and by decreased liver and adipose tissue n3/n6 PUFA ratios.
The diets selected for the present study were based on lard (predominantly SFA and MUFA) or flaxseed oil lipids (alpha linolenic acid [ALA]). Lard-based diets are known to be steatogenic in murine models, while flaxseed oil can attenuate non-alcoholic fatty liver in hyperlipidemic rodents. The specific aims of this study were to examine: (i) how diets based on lard or flaxseed oil affect the food intake, body fat stores, liver fat percent, and FA profiles of voles, (ii) whether the different diets could have effects on the rate of weight loss and the responses of liver biochemistry and histology to 18 h of fasting, (iii) if signs of inflammation and connective tissue activation (leukocytes and HA accumulation) are present in steatotic livers of voles, and (iv) how body composition and liver characteristics recover from food deprivation. Based on previous data, it was hypothesized that flaxseed oil n3 PUFA (dietary ALA and its derivatives EPA and DHA) could have beneficial effects on the prevention of fasting-induced fatty liver or on the recovery from steatosis.
In the present study, the dietary lipid source did not affect the appetite, weight gain, body or liver fat percent of the fed control voles. The fat content of the diets was 8 percent, and even though this was twice as high as that of the standard laboratory rodent chow fed previously to this vole strain, it did not induce liver fat accumulation. The higher proportion of 18:0 in the lard diet did not translate into clear differences in the liver profiles possibly due to its desaturation to 18:1n-9 and chain-shortening to 16:0.
In the lard diet, EPA, DPA n3, and DHA were slightly higher in proportion but their liver percentages were elevated in the flaxseed oil-fed voles.
n3 LCPUFA and n3/n6 PUFA ratios are reduced in livers of NAFLD patients. These changes were also observed in the lard-fed voles with fasting induced fatty liver, whereas the flaxseed oil fed animals showed reduced n3 LCPUFA proportions but elevated n3/n6 PUFA ratios presumably due to increased influx of ALA to the liver from TAG hydrolysis in adipose tissue. The ALA enriched diet, compared to the diet with a high SFA content, did not protect the voles from developing the fasting-induced fatty liver, nor did it ameliorate the severity of the hepatic fat accumulation. It is possible that the antisteatogenic effects of n3 PUFA could be species specific. Although the liver fat percent was the same in the fasted voles of both dietary regimes, the liver TAG concentration was higher in the fasted flaxseed group. This could suggest a more severe fatty liver in the flaxseed voles at the start of refeeding, and perhaps for this reason their recovery did not differ from that of the lard-fed voles.
To summarize, (i) the lard-based diet did not induce body or liver fat accumulation in the voles compared to the flaxseed oil lipids. The dietary FA composition was clearly reflected in the hepatic FA profiles of the fed animals, and (ii) fasting modified the liver FA composition to resemble more closely the dietary profile. This probably results from the mobilization of dietarily abundant FA from adipose tissues, their transportation to the liver, and esterification into TAG. The ALA-enriched diet was not effective in the prevention of fatty liver, and (iii) HA staining visualized in the portal fields showed no significant relation with steatosis development (iv) Flaxseed oil rich in ALA did not further accelerate the rapid recovery of the fasted voles from fatty liver. (Editors comments)
