triolein and Fatty-Liver

Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density lipoprotein secretion rate. Concomitantly, triglyceridemia was 13-fold greater than in controls. Hepatic carnitine palmitoyltransferase I activity and palmitate oxidation capacities measured in vitro were increased after treatment. Gene expression of hepatic proteins involved in fatty acid oxidation, triglyceride formation, and lipid uptake were all increased and were associated with increased hepatic free fatty acid content in treated rats. In periepididymal adipose tissue, mildronate markedly increased lipoprotein lipase and hormone-sensitive lipase activities in fed and fasted rats, respectively. On refeeding, carnitine-depleted rats exhibited a rapid decrease in blood triglycerides and free fatty acids, then after approximately 2 h, a marked drop of liver triglycerides and a progressive decrease in liver free fatty acids. Data show that up-regulation of liver activities, peripheral lipolysis, and lipoprotein lipase activity were likely essential factors for excess fat deposit and release alternately occurring in liver and adipose tissue of carnitine-depleted rats during the fed/fasted transition.

Topics: Adipose Tissue; Animals; Carnitine; Fatty Acids; Fatty Liver; Gene Expression Regulation; Hepatocytes; Lipids; Lipoprotein Lipase; Lipoproteins, LDL; Liver; Male; Rats; Rats, Wistar; Triolein

Fatty acid bile acid conjugates (FABACs) are a new family of synthetic molecules designed to solubilize biliary cholesterol. They were shown to prevent and dissolve cholesterol gallstones in inbred C57L/J mice fed a lithogenic, high-fat diet (HFD). In these mice, fatty liver was observed in the controls but not in the FABAC-treated ones. The present study was designed to study the effect of FABAC (arachidyl-amido-cholanoic acid) on diet-induced fatty liver in rats, hamsters, and mice. The fatty liver score (on a scale of 0-4 by light microscopy) was 4.0 in control hamsters and 0.3 in the FABAC-fed hamsters (P <.001). In mice it was 1.5 and 0.4, respectively (P <.01). The lipid/protein ratio in the liver was 1.3 +/- 0.44 (mg lipid/mg protein) in control rats and 0.66 +/- 0.04 in the FABAC group (P =.001) after 14 days. In hamsters it was 1.41 +/- 0.27 and 1.11 +/- 0.20, respectively (P =.03), after 21 days. In Imperial Charles River (ICR) mice the ratio was 0.34 +/- 0.10 and 0.17 +/- 0.07 (P =.03), respectively, after 24 days. Liver fat concentration, measured as mg lipid/g liver tissue, decreased similarly by FABAC feeding. The decrease in liver fat affected mainly the triglyceride levels. FABAC-fed animals gained weight similarly to the controls. Triglyceride absorption was unaffected by FABAC supplementation. In conclusion, oral FABAC therapy prevents/reduces the development of fatty liver in animals consuming a HFD.

Topics: Administration, Oral; Animals; Bile Acids and Salts; Body Weight; Cholic Acids; Cricetinae; Dietary Fats; Fatty Liver; Female; Liver; Male; Mesocricetus; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; Rats; Rats, Wistar; Triglycerides; Triolein; Tritium

We determined the relationship between microsomal triglyceride transfer protein (MTP) (activity, mass, and mRNA) and liver triglyceride concentration in 16 dairy cows (13 multiparous and three primiparous) from 27 d before expected calving (d -27) to 35 d postpartum (d 35), the time period when fatty liver is most likely to develop. In addition, dry matter intake, plasma nonesterified fatty acids (NEFA), and plasma glucose were monitored. There were no significant parity x time interactions. Dry matter intake, plasma NEFA, plasma glucose, and liver triglyceride were significantly affected by day of sampling. Dry matter intake was 10.7, 8.0, and 19.5 kg/d on d -27, 2, and 35, respectively. Plasma NEFA concentration was higher on d 2 (1113 microEq/L) compared with d -27 (201 microEq/L) and 35 (358 microEq/L). Plasma glucose concentration was 63.3, 54.3, and 57.8 mg/dl on d -27, 2, and 35, respectively. Hepatic triglyceride (TG) concentration increased from 1.8 to 11.8% liver TG (DM basis) on d -27 and 2, respectively. There was no difference between hepatic triglyceride concentration on d 2 and 35. There was a significant effect of day of sampling on hepatic MTP activity and mRNA. Hepatic MTP activity decreased from 2.08 to 1.79 nmole triolein transferred/ h per mg of microsomal protein on d -27 and 2, respectively, and increased from 1.79 to 2.17 nmole triolein transferred/h per mg of microsomal protein on d 2 and 35, respectively. Hepatic MTP mRNA increased from d -27 to 2 and remained elevated from d 2 to 35. There was no effect of day of sampling on MTP mass. There were no significant correlations between hepatic MTP activity, mass, or mRNA with either liver TG or plasma NEFA on any of the sampling days. The cause of a decrease in hepatic MTP activity and increase in mRNA on d 2 is unknown. However, the lack of correlation between MTP activity, mass, or mRNA with either liver TG or plasma NEFA on d 2 postpartum suggests that MTP probably does not play a role in the etiology of fatty liver that occurs in dairy cows at calving.

Topics: Animals; Blood Glucose; Blotting, Northern; Carrier Proteins; Cattle; Cattle Diseases; Diet; Eating; Fatty Acids, Nonesterified; Fatty Liver; Female; Liver; Male; RNA Probes; RNA, Messenger; Time Factors; Triglycerides; Triolein

Topics: Animals; BCG Vaccine; Calcinosis; Cerium; Chlorides; Fatty Liver; Female; Gadolinium; Mononuclear Phagocyte System; Palmitic Acids; Rats; Splenic Diseases; Triolein; Zymosan

Topics: Alcohol Oxidoreductases; Animals; Carbon Dioxide; Carbon Radioisotopes; Dose-Response Relationship, Drug; Ethanol; Fatty Acids; Fatty Liver; Humans; Intubation, Gastrointestinal; Liver; Male; Oxidation-Reduction; Portal System; Pyrazoles; Rats; Triglycerides; Triolein

Topics: Alcohol Oxidoreductases; Animals; Carbon Dioxide; Carbon Isotopes; Cholesterol; Ethanol; Fatty Acids; Fatty Liver; Liver; Male; Oxidation-Reduction; Pyrazoles; Rats; Respiration; Triglycerides; Triolein

Topics: Cholestasis; Fatty Liver; Humans; Intestinal Absorption; Iodine Isotopes; Liver Cirrhosis; Liver Neoplasms; Oleic Acids; Radiometry; Triolein