Potentiation of epinephrine-induced lipolysis in fat cells from estrogen-treated rats

We investigated concomitantly the effects of ethinyl-estradiol (EE₂) at low dose (1.2 μg/animal for 10 days) and high dose (120 μg/animal for 3 days) on body weight, weight of fat stores, triglyceridemia and fat cell lipoprotein lipase and hormone-sensitive lipase activities in female rats. At low dose, EE₂ increased triglyceridemia and lipoprotein lipase activity, whilst high dose decreased both parameters. At low and high doses, and regardless of whether triglyceridemia and lipoprotein lipase activity were increased and decreased, EE₂ caused depletion in fat stores. Fat cells isolated from depleted fat tissue elicited marked increases in the response of hormone-sensitivelipase to epinephrine. Taken together, the data suggest that the potentiation of epinephrine-induced lipolysis in fat cells is likely to represent a major cause to estrogen-induced fat depletion.     

Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells

Norepinephrine induced lipolysis in rat fat cells, in vitro, in a time- and concentration-dependent manner, without concomitantly increasing hormone-sensitive lipase (HSL) activity. It also induced, time and concentration dependently, HSL translocation from the cytosol to the lipid droplets in fat cells. Isoproterenol, forskolin, dibutyryl cyclic AMP, and theophylline also induced lipolysis in fat cells, but did not stimulate HSL activity. These agents also induced HSL translocation from the cytosol to the lipid droplets in fat cells: about 80% to 90% of all HSL was located in lipid droplets after incubation for 1 h.These results suggest that the critical event in lipolytic activation of fat cells induced by lipolytic agents is not an increase in the catalytic activity of HSL but translocation of HSL to its substrate on the surfaces of lipid droplets in fat cells.-Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. J. Lipid Res. 2001. 42: 120;-127.     

Dietary diacylglycerol suppresses high fat diet-induced hepatic fat accumulation and microsomal triacylglycerol transfer protein activity in rats

We have recently shown that the long-term ingestion of dietary diacylglycerol (DAG) mainly containing 1,3-isoform reduces body fat accumulation in humans as compared to triacylglycerol (TAG) with the same fatty acid composition. The fat reduction in this human experiment was most pronounced in visceral fat and hepatic fat. Recent animal studies have also indicated that dietary DAG induces alteration of lipid metabolism in the rat liver. In the present study, the dietary effects of DAG on high fat diet-induced hepatic fat accumulation and hepatic microsomal triglyceride transfer protein (MTP) activity were examined in comparison with those of TAG diet in rats. When the TAG oil content was increased from 10 to 30 g/100 g diet, hepatic TAG concentration, hepatic MTP activity and MTP large subunit mRNA levels were significantly increased after 21 days. However, when the dietary TAG oil (30 g/100 g diet) was replaced with the same concentration of DAG oil with the same fatty acid composition, the increase of the TAG concentration and the MTP activity in the liver were significantly less and the mRNA levels remained unchanged. The MTP activity levels correlated significantly with hepatic TAG concentration.These results showed that dietary DAG may suppress high fat diet-induced MTP activity in the liver, and indicated the possibility that hepatic TAG concentration may regulate hepatic MTP activity.     

Lag phase and hydrolysis mechanisms of triacylglycerol film lipolysis

We here present novel insights into the dynamic changes of a nanosized lipid film during enzymatic degradation. When adding an aqueous solution containing a triacylglycerol lipase to an approximately 100nm thin triolein film, which is supported on a hard surface, the film thickness, elasticity, viscosity, and chemical composition were obtained continuously. Both a mechanical technique (quartz crystal microbalance with dissipation monitoring) and a spectroscopic technique (attenuated total reflection Fourier transform infrared spectroscopy) were utilised for this study. Detailed data revealed the effects of pH, Ca(2+), and catalytic rate on lipolysis, including product release from the film. It was found that under basic conditions and without Ca(2+), the lipolytic activity commence instantaneously upon addition of enzyme, whereas product release from the substrate film awaits conditions that favours release. A model for removal of degradation products from the film is introduced, including a novel interpretation of the lag phase phenomenon.     

Gelucire44/14 improves fat absorption in rats with impaired lipolysis

Clinically relevant fat malabsorption is usually due to impaired intestinal fat digestion (lipolysis) and/or to impaired solubilization of the lipolytic metabolites. We hypothesized that Gelucire^®44/14 – a semi-solid self-micro-emulsifying excipient – could increase fat absorption. In relevant rat models for impaired lipolysis or for impaired solubilization we tested whether administration of Gelucire^®44/14 enhanced fat absorption. Rats with impaired lipolysis (lipase inhibitor Orlistat diet) and rats with reduced solubilization (permanent bile diversion) underwent a 72 h fat balance test to assess fat absorption. The absorption kinetics of a stable isotope-labeled fatty acid was assessed in rats with reduced solubilization, in the presence or absence of Gelucire^®44/14. Gelucire^®44/14 improved fat absorption in rats with impaired lipolysis (from 70% to 82%, p < 0.001). In rats with reduced solubilization, Gelucire^®44/14 did not increase fat absorption nor did it reconstitute the absorption kinetics of ¹³C-labeled palmitate, compared with control rats administered buffer without Gelucire^®44/14. The present data show that Gelucire^®44/14 might enhance fat absorption under conditions of impaired lipolysis, but not during impaired solubilization. We speculate that, due to its self-micro-emulsification properties, Gelucire^®44/14 stabilizes and improves residual lipolytic enzyme activity in vivo, which could be of therapeutic value in clinical conditions of fat malabsorption due to impaired lipolysis.     

Decreased serum lipids, serum insulin and triacylglycerol synthesis in adipose tissue of JCR:LA-corpulent rats treated with benfluorex

Rats of the JCR:LA-corpulent strain were treated with benfluorex daily at a dose of 25 mg/kg body weight. This strain of rat, if homozygous for the cp gene (cp/cp), is hyperphagous, obese, hypertriglyceridemic, insulin resistant and in the case of male rats, atherosclerosis prone. The benfluorex treatment produced a sharp reduction in food intake which remained suppressed despite recovery toward normal after 2 weeks of treatment. This was accompanied by sustained decreases in body weight and adipose tissue mass. The ability of adipose tissue from female rats to take up glucose and convert it to lactate, glyceride-glycerol and fatty acids was decreased. This decrease was largely due to decreased adipose tissue mass. The serum concentrations of glucose, lactate, triacylglycerol, cholesterol, phospholipids and insulin were decreased in both sexes. The treatment also improved glucose tolerance and decreased corticosterone concentrations in male rats only. While reduction of food consumption contributes to the effects seen, benfluorex clearly had significant direct metabolic effects. The effects are consistent with an improved insulin sensitivity leading to a decrease in circulating triacylglycerol. The changes produced by benfluorex are all in directions that should inhibit atherogenesis in this animal model for the human obesity/hypertriglyceridemia/insulin resistant syndrome.     

Membrane phospholipids and hormone-sensitive lipolysis in fat cells

Isolated fat cells from rats which have been made hypothyroid do not give a lipolytic response to catecholamines. A recent report has suggested that catecholamine-sensitive lipolysis may be correlated with an “unmasking” of receptors by linoleic acid rich phospholipids in the fat cell membrane. No apparent differences in phospholipid fatty acid composition could be found in membrane “ghosts” prepared from normal and hypothyroid rats.     

Resistin induces lipolysis and re-esterification of triacylglycerol stores, and increases cholesteryl ester deposition, in human macrophages

Human resistin, found within atheroma, exerts inflammatory, angiogenic and proliferative effects in vascular cells and may predict coronary events. Here, we investigate mechanisms by which resistin contributes to macrophage 'foam cell' formation. Increases in macrophage (THP-1) cholesteryl ester mass, in the presence or absence of oxidized LDL, were not explained by altered cholesterol efflux. Instead, resistin enhanced fractional turnover of the endogenous triacylglycerol pool, increased uptake and decreased oxidation of exogenous fatty acids, and decreased phosphorylation of acetyl CoA carboxylase, all factors increasing the availability of fatty acyl CoA substrate for acyl CoA: cholesterol acyltransferase-1, thereby enhancing macrophage cholesteryl ester deposition.     

Relationships among serum lipids,milk production and physiological status in dairy cows

• 1.1. Serum concentrations of cholesterol, triglyceride and alpha lipoprotein cholesterol were determined in nine Holstein cows during different stages of their gestation and lactation cycles.
• 2.2. Serum cholesterol concentrations and daily milk yields were significantly correlated during early and late lactation. The correlations were not significant over the entire lactation.
• 3.3. Maximum values for serum cholesterol were observed at mid lactation and minimum at or near parturition. Serum triglyceride concentrations ranged from 4 to 33 mg/dl. Although prepartum levels for triglyceride tended to be higher than postpartum concentrations, no correlation with milk yield was noted.
• 4.4. These data are compared with lipid changes which take place in other mammals during lactation.

     

Phosphatidylcholine composition of emulsions influences triacylglycerol lipolysis and clearance from plasma

Sonicated emulsions containing triolein, a specific phosphatidylcholine and cholesterol were prepared. Bolus doses were injected intravenously into rats and plasma clearance kinetics and organ uptakes were determined. Emulsion triacylglycerol lipolysis by rat heart lipoprotein lipase was measured in vitro. Phosphatidylcholine molecular species influenced emulsion metabolism in vivo and in vitro. Emulsions containing saturated phosphatidylcholines at temperatures below their melting points were poor substrates for lipoprotein lipase, compared with those stabilized by mixed chain phosphatidylcholines. Distearoylphosphatidylcholine stimulated hepatic uptake compared with emulsions made with egg yolk phosphatidylcholine, which modeled chylomicrons closely. Emulsion populations with the same surface compositions but with mean diameters of 700-800 A and 1100-1300 A were metabolized similarly, suggesting that, within the normal chylomicron size range, size alone does not determine the disposition of triacylglycerol-rich emulsions or lipoproteins.     

Muscle mitochondrial ultrastructure in exercise-trained iron-deficient rats

To investigate effects of endurance training and iron deficiency, as well as the combination of these two conditions, on mitochondrial ultrastructure, weanling rats at 3 wk of age were assigned to iron-deficient (Fe-) and iron-sufficient (Fe+) groups. Subsequently, groups were subdivided into exercise-trained (T) and sedentary (S) groups. Electron microscopy showed subsarcolemmal and intrafibrillar mitochondria in the Fe-T animals to be enlarged with sparse cristae and vacuole-like areas compared with the other groups. An increase in the number of lipid droplets in both Fe- groups was observed. Stereological measurements revealed a 99% increase in the volume occupied by muscle mitochondria in the Fe-T animals (11.9 +/- 0.8%) over the Fe+T (5.9 +/- 0.4%) and Fe+S (6.0 +/- 0.3%) groups and a 55% increase over the Fe-S groups (7.7 +/- 0.3%). The ratio of mitochondrial surface area to tissue volume was significantly decreased only in the Fe-T group. These results indicate that the combined stresses of iron deficiency and training produce mitochondrial ultrastructural changes far greater than those of iron deficiency or training alone. Because this is also the case with the disproportion among mitochondrial enzymes, it is possible that the ultrastructural changes are indicative of morphological responses that maintain ATP turnover during exercise in iron deficiency when oxygen transport and electron transport chain activities are reduced.     

Defects in triacylglycerol lipolysis affect synthesis of triacylglycerols and steryl esters in the yeast

Tgl3p, Tgl4p and Tgl5p are the major triacylglycerol lipases of the yeast Saccharomyces cerevisiae catalyzing degradation of triacylglycerols stored in lipid droplets. Previous results from our laboratory (Athenstaedt and Daum, 2005, J. Biol. Chem. 280, 37301–37309) demonstrated that a yeast strain lacking all three triacylglycerol lipases accumulates not only triacylglycerols at high amount, but also steryl esters. Here we show a metabolic link between synthesis and mobilization of non-polar lipids. In particular, we demonstrate that a block in tri-acylglycerol degradation in a tgl3?tgl4?tgl5? triple mutant lacking all major triacylglycerol lipases causes marked changes in non-polar lipid synthesis. Under these conditions formation of triacylglycerols is reduced, whereas steryl ester synthesis is enhanced as shown by quantification of non-polar lipids, in vivo labeling of lipids using [¹⁴C]oleic acid and [¹⁴C]acetic acid as precursors, and enzyme analyses in vitro. In summary, this study demonstrates that triacylglycerol metabolism and steryl ester metabolism are linked processes. The importance of balanced storage and degradation of these components for lipid homeostasis in the yeast is highlighted.     

Dietary fat and weight gain among women in the Nurses' Health Study

Objective: To assess the association of dietary fat and weight gain among adult women and to investigate whether offspring of overweight parents have a greater predisposition to weight gain due to intake of dietary fat. Research Methods and Procedures: This was an 8‐year follow‐up of 41,518 women in the Nurses’ Health Study (NHS), a population‐based, prospective cohort. The women were 41 to 68 years of age, free of cardiovascular disease, cancer, and diabetes in 1986 when “baseline” weight and diet were assessed. Eight years later (1994), changes in weight and dietary intake were assessed. Linear regression models were used to relate change in weight to fat intake and change in fat intake, using the percentage of energy from carbohydrate as the comparison, adjusted for age, BMI in 1986, leisure time physical activity, time spent sitting, percent of calories from protein, and change in percentage of calories from protein. Results: Overall, there was a weak positive association between total fat intake (β = 0.11) and weight gain. Increases in monosaturated and polyunsaturated fat were not associated with weight gain, but increases in animal fat, saturated fat, and trans fat had a positive association with weight change. There was not strong evidence of effect modification by parental weight status (p = 0.7 to 0.8 for percentage of calories from total fat, animal fat, and vegetable fat); however, the associations were stronger among the overweight compared with leaner women (p < 0.05 for percentage of calories from each type of fat). Among overweight women, for every one percentage increase in percentage of calories from trans fat, women gained an additional 2.3 lb (95% confidence interval, 1.80 to 2.86). Conclusion: Our results show that, overall, percent of calories from fat has only a weak positive association with weight gain; however, percentage of calories from animal, saturated, and trans fat has stronger associations. There was no clear evidence that the diet‐weight gain association was stronger among offspring of overweight parents, but dietary fat was associated with greater weight gain among overweight women.