Development Of Fatty Liver In Rats Research Articles

Effects of a high-fat low-carbohydrate diet under different energy conditions on glucose homeostasis and fatty liver development in rats and on gluconeogenesis in the isolated perfused liver.

The beneficial effects of high-fat low-carbohydrate (HFLC) diets on glucose metabolism have been questioned and their effects on liver metabolism are not totally clear. The aim of this work was to investigate the effects of an HFLC diet under different energy conditions on glucose homeostasis, fatty liver development, and hepatic gluconeogenesis using the isolated perfused rat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) was administered to rats for 4 weeks under three conditions: ad libitum (hypercaloric), isocaloric, and hypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liver were higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric and hypercaloric groups, although insulin sensitivity was not altered. HFLC diet also caused marked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reduced capacity to metabolize alanine, the latter effect being more intense in the hypocaloric condition. Thus, even when HFLC diets are used for weight loss, our data imply that they can potentially cause harmful consequences for the liver.

Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats

Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.

In vivo percutaneous reflectance spectroscopy of fatty liver development in rats suggests that the elevation of the scattering power is an early indicator of hepatic steatosis

This study assessed whether there was a scattering spectral marker quantifiable by reflectance measurements that could indicate early development of hepatic steatosis in rats for potential applications to pre-procurement organ evaluation. Sixteen rats were fed a methionine-choline-deficient (MCD) diet and eight rats were fed a normal diet. Direct assessment of the liver parenchyma of rats in vivo was performed by percutaneous reflectance spectroscopy using a single fiber probe at the beginning of diet-intake and arbitrary post-diet-intake times up to 11 weeks to render longitudinal comparison. Histological sampling of the liver over the duration of diet administration was performed on two MCD-diet treated rats and one control rat euthanized after reflectance spectroscopy measurement. The images of hematoxylin/eosin-stained liver specimens were analyzed morphometrically to evaluate the lipid size changes associated with the level of steatosis. The MCD-diet-treated group ([Formula: see text]) had mild steatosis in seven rats, moderate in three rats, severe in six rats, and no other significant pathology. No control rats ([Formula: see text]) developed hepatic steatosis. Among the parameters retrieved from per-SfS, only the scattering power (can be either positive or negative) appeared to be statistically different between MCD-treated and control livers. The scattering power for the 16 MCD-diet-treated livers at the time of euthanasia and presenting various levels of steatosis was [Formula: see text], in comparison to [Formula: see text] of the eight control livers [Formula: see text]. When evaluated at days 12 and 13 combined, the scattering power of the 16 MCD-diet-treated livers was [Formula: see text], in comparison to [Formula: see text] of the eight control livers ([Formula: see text]). All of four MCD-treated livers harvested at days 12 and 13 presented mild steatosis with sub-micron size lipid droplets, even though none of the MCD-treated livers were sonographically remarkable for fatty changes. The elevation of the scattering power may be a valuable marker indicating early hepatic steatosis before the steatosis is sonographically detectable.

Effect of betaine on the hepatic damage from orotic acid-induced fatty liver development in rats

Betaine prevents hepatic damage caused by ethanol and carbone tetrachloride (CCl4) in rats. Present study was to investigate the effect of betaine on the hepatic microsomal triglyceride transfer protein (MTP) mRNA expression in orotic acid (OA)-induced fatty liver in rats. OA feeding was attributed to the significant increase in the hepatic levels of triglyceride and the serum levels of ALT and AST and resulted in typical histology of fatty liver contained numerous largely fat droplets. While concomitant supplementation of betaine to OA diet was slightly reduced the hepatic triglyceride concentrations and was significantly decreased ALT activity. Hepatic MTP mRNA expression by OA treatment increased by 14% despite triglyceride accumulation in the liver in OA treatment rats relative to rats fed a normal diet without OA supplemented, but MTP expression by simultaneous supplementation of OA and betaine was slightly decreased by 7.9% as compared to the OA-feeding rats. A significant elevation of TBARS contents in the liver homogenate, microsome, and mitochondrial fractions of the OA-feeding rats compared with the normal rats, however, these increases were significantly or slightly decreased by simultaneous addition of OA and betaine. The increases of hepatic OA and betaine levels in OA feeding rats was also found when compared to the normal rats, but these increases were significantly lowered in the concomitant supplementation OA and betaine. The content of Fe was significantly increased in the OA feeding rats, but this elevation showed significantly recovered as low as the normal level by concomitant with OA and betaine. Zinc content was also significantly decreased in the OA feeding rats compared with the normal rats, but this reduction was more significantly elevated by concomitant with OA and betaine. Hepatic glutathione content in the OA feeding rats was similar to that of the normal rats, but this content was slightly reduced without statistically significant differences. But, a significant elevation in the hepatic glutathione content was found in the simultaneously administration OA and betaine. The hepatocytes contained numerous largely fat droplets induced by OA administration and was slightly reduced by simultaneous supplementation of OA and betaine. Present study demonstrated that betaine has a weak preventive action on the OA-induced triglyceride accumulation.