Liver Of Fat-fed Rats Research Articles

Antihyperlipidemic and antioxidant activities of the ethanolic extract of Garcinia cambogia on high fat diet-fed rats.

The study investigated the antihyperlipidemic and antioxidant activities of the ethanolic extract of Garcinia cambogia on high fat diet-fed rats. The phytochemical constituents, total polyphenol content and ferric reducing antioxidant power (FRAP) were estimated in the G. cambogia extract (GE). Male Wistar rats were fed with either standard rodent diet or 30% high-fat diet and administered with GE at a dose of 400 mg/kg body weight/day for 10 weeks. At the end, lipid profile and oxidative stress parameters were estimated. The analyses revealed the presence of carbohydrates, proteins, sterols, tannins, flavonoids and saponins in GE. The total polyphenol content and FRAP of GE were 82.82±7.64 mg of gallic acid equivalents and 260.49±10.18 µM FRAP per gram of the GE. High-fat feeding elevated plasma total cholesterol (TC), triacylglycerol (TAG), non-high-density lipoprotein-cholesterol (non-HDL-C), malondialdehyde (MDA), reduced HDL-C and blood antioxidants, glutathione (GSH), glutathione peroxidase (GPx), catalase. Increase in total oxidant status (TOS), oxidative stress index (OSI) and decrease in the total antioxidant status (TAS) were observed in plasma, liver and kidney of fat-fed rats. Administration of GE decreased food intake, plasma TC, TAG, non HDL-C, MDA, increased HDL-C and blood antioxidants GSH, GPx, catalase. GE also reduced TOS, OSI and elevated TAS in plasma and liver of fat-fed rats. Renal OSI was significantly reduced upon GE treatment. Our study demonstrated that GE is effective in ameliorating high-fat-diet-induced hyperlipidemia and oxidative stress.

Interrelationship in the regulation of pyruvate dehydrogenase and adenine-nucleotide translocase by palmitoyl-CoA in isolated mitochondria.

Full activation of rat liver pyruvate dehydrogenase in vitro by ADP was prevented by palmitoyl-CoA at a concentration sufficiently low to preclude substrate effects secondary to its oxidation by mitochondria. Activation of pyruvate dehydrogenase by ADP in livers of fat-fed rats was less than in the control animal. The results are consistent with the experiments demonstrating an inhibition of adenine nucleotide translocase and on increased intramitochondrial ATP/ADP ratio by palmitoyl-CoA which could account for the effect on pyruvate dehydrogenase. Inactivation of brain pyruvate dehydrogenase by ATP was also diminished by palmitoyl-CoA indicating that the effect was at the level of the adenine nucleotides rather than at either the pyruvate dehydrogenase kinase or phosphatase enzymes.

Fatty globulation in the liver of fat-fed rats studied by rolled films.

(1) Globules of fat in enormous numbers appeared in the liver cells of rats fed for three days on margarine or butter as their sole food. (2) This change was studied principally in rolled films of liver incubated for 2 hr at 38°C. Films of incubated fatty liver contained numerous entire hepatocytes in which cellular structure was visible with clarity and definition. In films made from fresh liver, most of the cells were ruptured. (3) The cells in films made from incubated livers of rats fed on margarine or butter showed intense fatty globulation. This change affected most of the cells and much of their cytoplasm was occupied by globules of liquid lipid. (4) Substantial, though less severe, fatty globulation was observed in similarly prepared hepatic films made from rats fed on cow's milk. (5) The cells seen in sections of frozen or wax-embedded liver of these fat-fed animals also contained fatty globules or (after wax-embedding) vacuolar spaces from which globular fat had been dissolved. But the disposition of droplets of lipid or spaces in sections of tissue, exposed to freezing and thawing or to infiltration by molten wax, may be very different from the state of hydrophobic lipid in the living cell. (6) The liquid globules seen ion rolled films, however, were not subjected to these artifactual hazards. The observations on globular fat in rolled films, therefore, confirm the assumption that globules of lipid visible in sections of fatty liver are a real entity of the living cell. (7) It is suggested that the neutral fat of normal liver cells is solubilized within micellar patticles and is thus invisible. The intense fatty globulation which occurs in liver cells of rats fed on margarine or butter probably arises because the amount of intracellular fat rapidly surpasses the quantity which can be solubilized in an invisible micellar state by the surfactants available within the cells. The excess of fat then rapidly forms an additional phase which becomes visible as conspicuous globules of liquid lipid.

Fatty acid metabolism in the perfused rat liver.

1. The formation of acetoacetate, beta-hydroxybutyrate and glucose was measured in the isolated perfused rat liver after addition of fatty acids. 2. The rates of ketone-body formation from ten fatty acids were approximately equal and independent of chain length (90-132mumol/h per g), with the exception of pentanoate, which reacted at one-third of this rate. The [beta-hydroxybutyrate]/[acetoacetate] ratio in the perfusion medium was increased by long-chain fatty acids. 3. Glucose was formed from all odd-numbered fatty acids tested. 4. The rate of ketone-body formation in the livers of rats kept on a high-fat diet was up to 50% higher than in the livers of rats starved for 48h. In the livers of fat-fed rats almost all the O(2) consumed was accounted for by the formation of ketone bodies. 5. The ketone-body concentration in the blood of fat-fed rats rose to 4-5mm and the [beta-hydroxybutyrate]/[acetoacetate] ratio rose to 11.5. 6. When the activity of the microsomal mixed-function oxidase system, which can bring about omega-oxidation of fatty acids, was induced by treatment of the rat with phenobarbitone, there was no change in the ketone-body production from fatty acids, nor was there a production of glucose from even-numbered fatty acids. The latter would be expected if omega-oxidation occurred. Thus omega-oxidation did not play a significant role in the metabolism of fatty acids. 7. Arachidonate was almost quantitatively converted into ketone bodies and yielded no glucose, demonstrating that gluconeogenesis from poly-unsaturated fatty acids with an even number of carbon atoms does not occur. 8. The rates of ketogenesis from unsaturated fatty acids (sorbate, undecylenate, crotonate, vinylacetate) were similar to those from the corresponding saturated fatty acids. 9. Addition of oleate together with shorter-chain fatty acids gave only a slightly higher rate of ketone-body formation than oleate alone. 10. Glucose, lactate, fructose, glycerol and other known antiketogenic substances strongly inhibited endogenous ketogenesis but had no effects on the rate of ketone-body formation in the presence of 2mm-oleate. Thus the concentrations of free fatty acids and of other oxidizable substances in the liver are key factors determining the rate of ketogenesis.

Regulation of gluconeogenesis by fatty acid oxidation in isolated perfused livers of non-starved rats.

The effects of intraportal infusion of 0.18–7.20 mmole/h of sodium caproate on gluconeogenesis were studied in isolated perfused livers of fed male rats. Even 0.18 mmole/h of sodium caproate enhanced the incorporation of carbon from the C-2 and the C-1 position of the pyruvate-lactate pool into glucose and glycogen, increased the specific activity of glucose and glycogen, and stimulated the net uptake of lactate and pyruvate as well as the net production of glucose. Net changes in liver glycogen concentration were the same with and without the infusion of caproate. With 0.72 mmole/h of sodium caproate, the ratio of carbon incorporated into glucose to carbon incorporated into CO2 had increased about 8 times for carbon from the C-2 position and about 4 times for carbon from the C-1 position of the lactate-pyruvate pool. An increase in the lactate/pyruvate and the β-hydroxybutyrate/acetoacetate ratio in the liver and in the perfusion medium occurred only with 0.72mmole/h or more of sodium caproate, whereas the CoASH/CoASAc ratio had already been decreased significantly with 0.18 mmole/h. A similar decrease in the CoASH/CoASAc ratio was observed in vivo in livers of fat-fed rats. Fat-feeding led to a 300% increase in the steady-state concentration of CoASH plus CoASAc in vivo, whereas the steady-state concentration of CoASH plus CoASAc in perfused livers did not change either with or without caproate. In contrast to this, the total concentration of ATP plus ADP was decreased by 40–50% after 30 min of perfusion with and without caproate. The ATP/ADP ratio was not changed by the intraportal infusion of caproate. From this it has been concluded, that: 1 The primary mechanism by which fatty acids enhance gluconeogenesis is a stimulation of the pyruvate carboxylase reaction and an inhibition of pyruvate oxidation. This is accomplished by an increase in the steady-state concentration of CoASAc and a decrease in the CoASH/CoASAc ratio, rather than a stimulation of the triosephosphate dehydrogenase reaction by a decreased cytoplasmic NAD+/NADH ratio. 2 The chance that oxaloacetate formed by carboxylation of pyruvate will be converted to phosphoenolpyruvate is higher in liver than in kidney. 3 Changes in the ATP/ADP ratio are not directly related to the regulation of gluconeogenesis by fatty acid oxidation.