Manifestations of Fasting-Induced Fatty Liver and Rapid Recovery from Steatosis in Voles Fed Lard or Flaxseed Oil Lipids

Abstract

Long-chain n-3 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 18:3n-3) affect liver fat-% 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 n-3 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-% increased to 22% 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 n-3 PUFA in both dietary regimes and n-3/n-6 PUFA ratios in the lard-fed voles. Decreases in long-chain n-3 PUFA may promote lipid accumulation by modulating the expression of lipid-metabolizing genes. Dietary 18:3n-3 did not prevent the development or attenuate the manifestation of steatosis in the fasted voles or promote the recovery.

De novo lipogenesis is suppressed during fasting but upregulated at population decline in cyclic voles

“…depletion of long-chain n-3 PUFA) are also shared by both. 4,5,19 DNL exacerbates steatosis in humans 6 but not in voles, which may be related to the different availability of carbohydrate-based substrates.…”

“…4 Some correlations between ACC1/FAS mRNA and particular FA may not have been causal but confounded by the mobilization of lipids from adipose tissue to be transferred into liver as NEFA and by the decreases that occurred in hepatic proportions of some FA due to fasting. 4,5 As it is known that PUFA can inhibit the induction of ACC and FAS in rats, 17 the elevated NEFA available for vole livers could have affected the rate of DNL. Although not analyzed in the present study, one possible path of transmission could be via the suppression of sterol regulatory element-binding protein 1 by 20:5n-3 and 22:6n-3.…”

“…7 In addition to macrovesicular steatosis, the vole fatty liver has FA manifestations similar to NAFLD, including decreased hepatic proportions of long-chain polyunsaturated fatty acids (PUFA), especially n-3 PUFA. 4,5 This has important ramifications, as the depletion of n-3 PUFA can shift the balance from TAG hydrolysis to FA synthesis and reduce VLDL secretion, thus enhancing lipid accumulation.…”

“…2,4 Despite the different etiologies (food deprivation vs. human obesity), the lipid accumulation in voles shares similarities with that of human non-alcoholic fatty liver disease (NAFLD). 2,5 A primary cause for both seems to be the high influx of nonesterified fatty acids (NEFA) into the liver due to lipid mobilization (fasting 2,4 ) or as an aspect of the metabolic syndrome (obesity 6 ). This can overwhelm the ability of the liver to utilize the fatty acids (FA) for energy production or to secrete them in very-low-density lipoprotein (VLDL).…”

Evidence of endoplasmic reticulum stress and liver inflammation in the American mink Neovison vison with benign hepatic steatosis

“…Slides were sealed using an automatic coverslipper (Tissue Tek Automatic Coverslipper, Somagen, Miles/Sakura, Japan). A third set of slides was processed for hyaluronan (HA) detection (Tammi et al 2005) in order to evaluate the presence of liver inflammation and connective tissue activation (Gerdin and Hällgren 1997;Oikari et al 2012) as described by Mustonen et al (2013). Evaluation of the HE-and HA-stained liver slides was carried out by a consultant pathologist who examined the slides three times at 400× magnification under a light microscope (Leica DM LB, Leica Microsystems, Heerbrugg, Switzerland).…”