Metabolism of free fatty acids in fatty tissue

Hyperlipacidaemias play a role as etiological partial factor in the pathogenesis of various acute and chronic functional disturbances and are essentially the sequel of a disturbed metabolism of the free fatty acids of the fatty tissue. With regard to its clinical relevance a survey is given of the free fatty acid metabolism of the fatty tissue and its free fatty acid net balance as resultants from lipolysis and triglyceride synthesis is described. The author deals with the regulation of the lipolysis by cyclic mononucleotides, adenosine triphosphate, adenosine, fatty acids, ions, beta-hydroxybutyrate, lactate as well as hormones and finally with the control of the triglyceride synthesis.     

Metabolism of free fatty acids in muscles

The skeletal muscle and the myocardium (musculature) are involved in the turnover rate of free fatty acids (FFA) with a third. Disturbances of the FFA metabolism of the musculature result in a restriction of the function which appears as a diminished contractility and, as far as the myocardium is concerned, additionally as arrhythmias. Moreover the restriction of the FFA utilization by the muscles plays a role in the origin of hyperlipacidaemias participating in the pathogenesis of various acute and chronic extramuscular functional disturbances (e.g. thrombophilia, disorders of the capillary circulation, hyperlipoproteinaemia, postnatal hypoglycaemia). With regard to its clinical relevance a survey is given of the FFA muscular metabolism. The author deals with the factors affecting the FFA netto bilance of the muscles and in this connection the regulation of the lipolysis, the triglyceride synthesis and the fatty acid oxidation. Finally the relation between the FFA and glucose metabolism in the muscles is described.     

Myocardial tissue free fatty acids

Myocardial ischaemia, whether produced by coronary artery ligation or by hypoxic low-flow perfusion of the isolated rat heart, has been shown to be associated with a significant depression in mitochondrial function, as well as an increase in tissue free fatty acid (FFA) levels. Although the effects of FFA on mitochondrial oxidative phosphorylation function in vitro are well established, it has not yet been shown that increased tissue FFA levels are causing the depression in mitochondrial function in ischaemia. Using the isolated perfused rat heart, several experiments were performed to gain more information regarding (i) the validity of the Dole FFA extraction technique; (ii) controlling factors; (iii) the relationship between tissue FFA and mitochondrial function and (iv) sources of tissue FFA in ischaemia. Significant elevation of tissue FFA was achieved by perfusion with (i) substrate-free Ringer and (ii) phosphatidylcholine. Elevation of tissue FFA obtained by perfusing with long-chain fatty acids was due to extracellular accumulation. Reduction of tissue FFA levels was observed by perfusing with (i) albumin, (ii) glucose, insulin and propranolol. Our results also suggest that lysosomal involvement could cause the increase in tissue FFA levels in myocardial ischaemia.     

The metabolism of free fatty acids in the liver

The liver participates in the turnover rate of free fatty acids (FFA) with a third. A severe disruption of liver function that occurs in cirrhosis leads therefore to a pathogenetic relevant hyperlipacidaemia respectively increases that. With regard to its clinical relevance a survey is given of the FFA metabolism of the liver. The factors are described which influence the FFA uptake by this organ. In this connection the metabolic fate of the FFA in dependence on the hormonal nutritive state is depicted. The author deals with the relation of the hepatic FFA metabolism to that of triglycerides, cholesterol, ketone bodies, carbohydrates, amino acids and insulin. The importance of these relatons for the caloric homeostasis and for the pathogenesis of various acute and chronic functional disturbances (ketoacidosis, negative nitrogen-balance, hyperlipoproteinaemia, hyperinsulinism, atherosclerosis) is described.     

以游离脂肪酸为结合配体的GPCRs的研究进展

食物营养成分在肠道中可被分解产生游离脂肪酸.游离脂肪酸除了被吸收氧化分解产生能量供机体利用外,还能通过结合脂肪酸受体激活信号通路,参与多种生理功能的调节,如维持能量平衡、代谢稳态、调节脂质形成与分解、影响机体免疫、结识流动消化成分间接监测菌群数量等.被确认的游离脂肪酸受体包括结合长链脂肪酸的G蛋白偶联受体(GPR)12...     

The role of free fatty acids in the pathogenesis of arteriosclerosis

Several diseases and functional disturbances (e.g. diabetes mellitus, obesity, phaeochromocytoma, chronic renal functional disturbances, psychosocial stress) marked by a disturbed metabolism of free fatty acids (FFA) and a hyperlipacidaemia correlate with a premature occurrence of arteriosclerotic alterations of the vessels. The FFA do not play an unimportant role as a link in the causal chain between the above-mentioned diseases or functional disturbances on the one hand and the atherogenesis on the other. Therefore an overview is given of the influence of a hyperlipacidaemia on important partial processes of the atherogenesis. In this connection the role of FFA in the lesion of the endothelium and in the formation of foam cells is depicted.     

Metabolism of long-chain polyunsaturated fatty acids in rat kidney cells

The metabolism of long-chain polyunsaturated fatty acids is characterized in tissues, such as liver and heart, especially from studies based on isolated cells incubated with radiolabelled fatty acid substrates. Differently, only little is known about the metabolism of fatty acids in the kidney. It is controversial whether the kidney possesses the ability to desaturate long-chain fatty acids or whether kidney cells are dependent on performed polyunsaturated fatty acids transported from the liver. In this study we used isolated rat kidney cells obtained by a perfusion technique. The cells were incubated with [1-(14)C]-labelled 18:3(n-3) or 20:3(n-6) fatty acids which were incorporated into complex lipids or desaturated/elongated. The lipids were separated by thin-layer chromatography and high-performance liquid chromatography. The present study shows that isolated kidney cells take up and esterify labelled long-chain polyunsaturated fatty acids in a time- and concentration-dependent manner. We have also demonstrated that isolated rat kidney cells only to a minor extent Delta6-desaturate labelled 18:3(n-3) to 18:4 (n-3). Conversely, the Delta 5-desaturation of 20:3(n-6) to 20:4(n-6) is far more active. It may thus be concluded that the kidney, at least in part, must obtain its C(20) and C(22) fatty acids from the circulation, while the active Delta5-desaturase suggests that preformed C(20) fatty acids can be converted to more unsaturated homologues in the kidney.     

Mass fragmentographic determination of myocardial free fatty acids

In contrast to plasma free fatty acids (FFA) remarkably little work has been carried out on myocardial FFA content directly. Reported values of normal FFA content vary so widely (29.0 to 25 000 nmol/g wet wt) that clearly the usual methods for the determination of FFA are difficult or not at all applicable to myocardial tissue. A method has been developed for the mass fragmentographic determination of myocardial FFA content and distribution and has been validated for sensitivity, reproducibility, specificity, recovery, cross-reaction with other lipids and reliability.The FFA content of normoxic canine myocardium was found to be 55.6 ± 20.2 nmol/g wet wt. This value is considerably below most of the previously reported values and much of the reported work on myocardial FFA content and changes must be re-examined.     

Acute regulation of adiponectin by free fatty acids

Little is known about the acute regulation of adiponectin in humans. In animal studies, adiponectin increases the clearance of free fatty acids (FFA) from the circulation by increasing skeletal uptake and oxidation of lipid, thereby regulating the FFA concentration. However, it is unknown if FFA regulate adiponectin. The aim of the present study was to investigate the effect of an acute reduction in free fatty acids on adiponectin concentration in healthy subjects. Ten normal male subjects were admitted for 2 inpatient visits and randomized to receive either acipimox (500 mg orally at 2 am and again at 6 am) or placebo on the first visit and vice versa on the second visit. Adiponectin, FFA, insulin and glucose were measured at 7:45 am. FFA concentrations were significantly lower after acipimox than placebo administration (0.08 +/- 0.02 mEq/L v 0.35 +/- 0.53 mEq/L, P <.05). Adiponectin concentrations were also significantly lower after acipimox than placebo administration (7.4 +/- 1.2 microg/mL v 10.3 +/- 1.7 microg/mL, P <.05). The change in FFA between acipimox and placebo correlated significantly with the change in adiponectin (r = 0.66, P <.05), eg, the larger the reduction in FFA in response to acipimox, the larger the reduction in adiponectin. These results suggest that acute lowering of FFA is associated with decreased adiponectin concentrations.     

Individual free fatty acids in patients with liver disease

The total free fatty acids, blood glucose, and individual free fatty acids were studied in 8 patients with viral hepatitis and 13 with cirrhosis. The results were compared with those obtained in 9 normal control subjects. Free fatty acids were significantly elevated in liver patients as compared with normal controls. A fall in free fatty acids following ingestion of amino acids and dextrose was noted in normal subjects as well as liver patients. Glucose tolerance test, when done on patients with liver disease, was abnormal in most cases. Highly significant differences were found in the composition of individual free fatty acids in liver patients as compared with normal subjects. Arachidonic and linoleic acids were decreased, while monounsaturated and saturated fatty acids were increased in patients with viral hepatitis and cirrhosis. No significant changes were noted in the percent composition of individual free fatty acids following ingestion of amino acids and dextrose.Decreased.     

Effects of free fatty acids on insulin secretion in obesity

The prevalence of obesity in Western society has reached epidemic proportions and its aetiological role in the development of type 2 diabetes has made finding an effective treatment for the condition of crucial importance. Of the many consequences of obesity, derangements in glucose metabolism present one of the greatest problems to health. While the role of obesity in causing insulin resistance has received much attention, the effect of obesity on β‐cell failure and the consequent development of type 2 diabetes requires re‐emphasis. In this review, the current understanding of the effects of elevated free‐fatty acids on β‐cell function will be examined, including a discussion of potential mechanisms. In particular, dysregulation of biochemical pathways and alterations in key enzymes, proteins and hormones will be considered as grounds for the progression to a diabetic phenotype.