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At least 19 recordsLinked to original sources
PubMed1975

Regulatory function of pyruvate dehydrogenase and the mitochondrion in lipogenesis.

The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower "energy pressure" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process.

Acetates↗
PubMed1975

Inhibition of hepatic lipogenesis by adenine nucleotides.

Incubation of liver slices and isolated liver cells with adenosine cyclic-3',5'-monophosphate at concentrations which inhibit lipogenesis was found to expand the pool size of the noncyclic adenine nucleotides in the intact cells of the preparations. This observation led to studies which demonstrated that adenosine and adenosine-5'-monophosphate also inhibited lipogenesis and expanded the adenine nucleotide pool size. It is proposed but not proven that the increase in intracellular nucleotides produced by adenosine-5'-monophosphate, adenosine cyclic-3',5'-monophosphate, and adenosine may have an adverse effect upon the synthesis of fatty acids. Because of the expansion of the adenine nucleotide pool size, high concentrations of adenosine cyclic-3',5'-monophosphate should not be used to investigate the mechanism responsible for hormonal regulation of lipogenesis. As an added complication, exogenous adenosine-5'-monophosphate was found to produce a small but significant increase in the intracellular concentration of adenosine cyclic-3',5'-monophosphate of isolated liver cells. This effect also may be a factor in the inhibition of lipogenesis by adenosine-5'-monophosphate. Low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate were found to inhibit lipogenesis without increasing the intracellular adenine nucleotide content of either liver slices or isolated liver cells. It is concluded that studies on the mechanism of glucagon regulation of lipogenesis should be carried out with glucagon or low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate.

Adenine Nucleotides↗
PubMed1976

Sebaceous lipogenesis in human skin. Variability with age and with severity of acne.

Lipogenesis from [14C] glucose was measured in skin biopsies from the shoulder-blade region of forty-two male subjects. In the acne age range, dermal lipogenesis showed an upward trend with increasing severity of acne; a similar trend was found in forehead sebum excretion rate, but no correlation was obvious between dermal lipogenesis (back) and sebum secretion rate (forehead) in the same subject. In older subjects, dermal lipogenesis was significantly increased in those with a past history of severe acne. At high rates of dermal lipogenesis there was a small but significant increase in wax ester labelling relative to triglyceride and squalene. No increase was found in squalene labelling relative to other lipids, either with increasing lipogenic rate or in severe acne. Dermal and epidermal lipogenesis rates showed no correlation with age. In dermis, however, there was a decrease in wax ester labelling relative to triglyceride, and a marked decrease in squalene labelling relative to both triglyceride and wax esters, with increasing age.

Acne Vulgaris↗
PubMed1979

Cyclic AMP and lipogenesis in fat cells from thyroidectomized rats.

Thyroid hormones regulate lipid metabolism by affecting lipogenesis as well as lipolysis. The present paper discusses the way thyroidectomy induced an enhancement in lipogenesis in rat fat cells. The doubling in the conversion of glucose to CO2 and fatty acids seen after thyroidectomy was found to be due to a modification in the actual pathway of glucose metabolism: there was a preferential stimulation of the conversion of glucose to CO2 by the pentose cycle (utilisation of [1-14C]glucose) while the production of fatty acids and glyceride-glycerol proceeded, respectively, much more, or only slightly more, via the pathway of [6-14C]glucose metabolism. Studies employing the phosphodiesterase inhibitor MIX, or the cyclic AMP analogue, DBcAMP showed that the lipogenic process depends on cyclic AMP. As the stimulatory effect of thyroidectomy was not abolished, however, lipogenesis must be under the independent control of both cyclic AMP and absence of thyroid hormones. Insulin, a further mediator of lipogenesis was found to further enhance the already preexisting high conversion of glucose to CO2 in fat cells from thyroidectomized rats. It is concluded that at least three factors modify lipogenesis: thyroidectomy, cyclic AMP and insulin; each achieving its effect in an independent manner.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Lipogenesis in situ in the genetically obese Zucker fatty rat (fa/fa): role of hyperphagia and hyperinsulinaemia.

In situ fatty acid synthesis has been measured with 3H2O in anaesthetised lean and obese Zucker (fa/fa) rats. The accumulation of fatty acids was increased in both the liver and adipose tissue of young fa/fa rats as a result of both an increased rate of lipogenesis and an increase in tissue mass. Whereas total hepatic lipogenesis increased with age, total adipose tissue lipogenesis decreased in older fa/fa rats. Experiments with hepatectomized rats showed that the liver was the major site of the excess fatty acid synthesis in fa/fa rats. The enhanced rate of lipogenesis in fa/fa rats was abolished by either pair-feeding or streptozotocin treatment. The results suggest that the increased fatty acid synthesis in fa/fa rats is secondary to the hyperphagia, hyperinsulinaemia, and increased mass of hepatic and adipose tissues.

Adipose Tissue↗
PubMed1977

Inhibition of lipogenesis by halothane in isolated rat liver cells.

1. Halothane at clinically effective concentrations [2.5 and 4% (v/v) of the gas phase of the incubation flask] was found to inhibit significantly lipogenesis from endogenous substrates, e.g., glycogen, or from added lactate plus pyruvate. This was accompanied by a decrease in the ratio of the free [NAD+]/[NADH] of the mitochondrion and the cytoplasm, as shown by the [3-hydroxybutyrate]/[acetoacetate] ratio and the [lactate]/[pyruvate] ratio. 2. Acetoacetate or pyruvate decreased the inhibitory effect of halothane and restored lipogenesis to control rates. They were reduced rapidly by 3-hydroxybutyrate dehydrogenase or lactate dehydrogenase respectively, with the concomitant oxidation of NADH and the generation of NAD+. 3. These results suggest that the mechanism by which halothane inhibits lipogenesis from glycogen or lactate is by inhibition of the oxidation of NADH; this results in inhibition of flux of carbon through pyruvate dehydrogenase and a shortage of acetyl-CoA for fatty acid synthesis. Thus when NADH acceptors are added in the presence of halothane, the concentration of mitochondrial NAD+ is raised so that the flux of carbon through pyruvate dehydrogenase increases and lipogenesis is restored.

Acetoacetates↗
PubMed1976

Effect of hypophysectomy and insulin on lipogenesis in cockerels.

Hypophysectomy increases hepatic lipogenesis in cockerels. In an attempt to find the possible hormonal mechanism for this we have examined the effects of hypophysectomy, insulin and pituitary homogenates on hepatic lipogenesis. Insulin (5 U/kg) injected intravenously, simultaneously with glucose-14C tracer, increased the amount of 14C found in liver lipids at 30 min after the injection. Similarly, insulin injected 5 min before killing, increased the incorporation of glucose-14C and acetate-14C by liver slices during a 30 min incubation. Hypophysectomy increased lipogenesis within 24 hours. The effect of insulin was most pronounced in hypophysectomized cockerels. The activity of the lipogenic enzyme, acetyl CoA carboxylase was similarly affected. A homogenate of chicken pituitaries added to the medium reduced lipid synthesis from glucose-14C by liver slices. This effect was larger in liver slices in which lipogenesis had been stimulated by insulin. The increased rate of hepatic lipgenesis in hypophysectomized cockerels may be caused partly by increased hepatic sensitivity to the lipogenic action of insulin or by the removal of a direct inhibition by pituitary hormones.

Acetyl-CoA Carboxylase↗
PubMed1979

Circadian phase-dependent prolactin mechanisms in hepatic lipogenesis of a teleost.

In the teleost, Fundulus grandis, injections of prolactin early in the light phase cause an immediate 50% depression in the rate of hepatic lipogenesis ([14C]acetate incorporation); 10 h later, that rate has returned to levels not different from controls. Injections of prolactin late in the light phase cause an even more dramatic immediate depression of lipogenesis (79%) followed by a gradual increase in lipogenic rate which is 2.6 times higher than the control rate after 24 h. The stimulation of lipogenesis by prolactin is blocked by simultaneous treatment with indomethacin, an inhibitor of prostaglandin synthesis. These circadian phase-dependent effects of prolactin on hepatic lipogenesis are discussed with reference to possible mechanisms of action exerted by endogenous prolactin rhythms.

Acetates↗
PubMed1976

Effect of maternal diet on fetal hepatic lipogenesis.

The effects of: a, maternal diet; b, cyclic-3',5'-adenosinemonophosphate (cyclic AMP) and c, clofibrate on hepatic lipogenesis in fetal rats were studied. The experimental diets contained 22% protein, 40--50% carbohydrate, adequate vitamins, and minerals. In addition, the fat-containing diets were supplemented with either 15% corn oil, 25% corn oil, or 5% cholesterol + 10% oleic acid. In the clofibrate feeding studies, 0.3% (w/v) of the ethyl ester was added to a stock ration or to fat-free diet. Lipogenesis was measured in liver slices incubated with [2-14C]pyruvate, [1-14C]acetate, or 3H2O. In addition, activities of lipogenic enzymes were measured in cytosol fractions from liver homogenates. The effec-s of the experimental diets on liver composition were also examined. Lipogenic activity was higher in fetal than in maternal liver. When 15% corn oil was added to the maternal diet, fatty acid synthesis in fetal liver did not decrease as it did in maternal liver. Maternal fasting decreased fetal fatty acid synthesys by 50% when measured with 14C and less than 10% when measured with 3H2O. Although the addition of cholesterol to the maternal diet decreased cholesterol synthesis in maternal liver, no such decrease was observed in fetal liver. Changes in enzyme activities paralleled alterations in lipogenesis in maternal but not in fetal liver. Corn oil feeding or fasting increased the rate of transfer of linoleate from the dam to the fetus. However, accumulation of linoleate in fetal liver did not correlate with a decreased rate of fatty acid synthesis as it did in maternal liver. Maternal hepatic glycogen stores were depleted by fasting, but glycogen levels in fetal liver remained high under these conditions.

Acetates↗
PubMed1979

The control of lipogenesis by dietary linoleic acid and its influence on the deposition of fat.

The replacement of dietary starch by sucrose results in an increase in hepatic lipogenesis in the rat. When corn oil (4% by weight or 9% of the energy content of the diet) was included with the sucrose (20% by weight, 20% of the energy content) the lipogenic effect of the sucrose was completely suppressed. In contrast, when beef tallow replaced the corn oil, the induced activity caused by the sucrose was reduced by only approximately 20%. No significant differences were observed between males and females. These diets containing sucrose supplemented with either 4% (w/w) corn oil or 4% (w/w) beef tallow, were then used to ascertain whether or not the effects on hepatic lipogenesis were reflected in changes in the amount of fat deposited during growth from 4--24 weeks of age. It was shown that the percentage body fat was only statistically different (P less than 0.05) when animals fed sucrose-supplemented diets were compared with animals fed diets supplemented with sucrose and beef tallow. However, there were no significant differences in total carcass weight of these rats. The results are discussed in terms of the relative contribution of liver and adipose tissue to total lipogenesis and the factors which control the lipogenic activity in the two tissues.

Animals↗
PubMed1976

Enzymes related to lipogenesis in the adipose tissue of obese subjects.

In a group of ten adult obese subjects, maintained for 15 days on a normal caloric intake and balanced diet, the activity of hexokinase (EC 2.7.1.1),6-phosphofructokinase (EC 2.7.1.11), and ATP citratelyase (EC 4.1.3.8) in the adipose tissue was significantly increased, both on a protein and on a fat cell number basis, compared to matched normal subjects. The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), malate dehydrogenase (EC 1.1.1.37), and malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40), on the other hand, was unchanged. Since both hexokinase and 6-phosphofructokinase are rate-limiting in glycolysis, their enhanced activity would indicate the occurrence of an increased capacity to metabolize glucose and therefore to generate alpha-glycerophosphate. The elevation of ATP citrate-lyase would suggest increased lipogenesis, owing to the regulatory role that this enzyme plays in fatty acid synthesis. The normal activity of glucose-6-phosphate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), which supply NADPH for the reduction of acetyl-CoA to fatty acids, would suggest that the change in lipogenesis is of moderate degree, thereb) affecting only the most rate-limiting enzyme, ATP citrate-lyase. These data, on the whole, are consistent with the occurrence of enhanced triglyceride formation. Whether the enzyme changes observed are adaptive or genetic in nature remains to be clarified.

ATP Citrate (pro-S)-Lyase↗
PubMed1977

Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities.

1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis.

Acetate-CoA Ligase↗
PubMed1976

Stoppage of glycogenesis and "over-shoot" of induction of lipogenesis and its related enzyme activities in the liver of fasted-refed rats.

To elucidate the causes of changes of carbohydrate metabolic pathways, the time course of utilization of dietary [U-14C]sucrose and induction of enzyme activities in the livers of rats were investigated. Adult male rats of BHE strain were refed after a fast of 2 days. The nutritionally complete refeeding diet contained 60% sucrose as the only source of carbohydrate. [U-14C]Sucrose was included in the diet on either day 1 or day 2, or both of refeeding. During the first day of refeeding, the radioactivity was incorporated mainly into liver glycogen which rose to over 100 mg/g. During the second day, little 14C appeared in the liver glycogen, which decreased sharply while glucose-6-phosphatase activity increased. The glycogenic pathway thus appeared to be blocked. On the other hand, 14C incorporation in the liver fat was minimal during the first day, but was quite extensive during the second day of refeeding. The enhanced lipogenesis was accompanied by large increases of activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-malic dehydrogenase. Results clearly indicate that the carbohydrate load in the liver of intact animals was initially metabolized by the glycogenic pathway. When glycogenesis stopped, carbohydrate was metabolized differently. The enhanced incorporation of [U-14C]sucrose into liver lipids indicates an increased formation of acetyl CoA and an accelerated formation and use of NADPH, probably from increasing dehydrogenase activities. Our data suggest that the blockage of synthesis of glycogen with the continuation of carbohydrate load was a primary cause in over-shooting induction of hepatic dehydrogenase activities and lipogenesis.

Adipose Tissue↗
PubMed1976

[Fetal and neo-natal development of brown adipose tissue in guinea pigs and rats. Feto-maternal or milk transfer of essential fatty acids : lipogenesis and morphology (author's transl)].

Brown adipose tissue (BAT) lipogenesis (fatty acid, glycerol and CO2 synthesis) and its morphology determined by optical microscopy, were studied in guinea pigs and rats during intra-uterine life and during the suckling period. Following the receptor induction and after the commencement of the hormone sensitive adenylate-cyclase/lipase system (i.e. on the 60th day in guinea pigs, on the 20th day in rats), the fetal BAT releases fatty acids (NEFA) and is capable of allowing the non-shivering thermogenesis. When the maternal diet and, consequently, the fetal or neonatal BAT are supplied with considerable linoleic acid, NEFA contain a large proportion of essential fatty acids. In vitro, the greater the linoleic acid concentration in these NEFA, the less inhibited is the lipogenesis from (2-14C) pyruvate. Thus, in periods just preceding or succeeding birth, fatty acid and glycerol synthesis are higher when the feto-maternal and/or the milk supply are enriched in linoleic acid than when they contain a large proportion of endogenous fatty acids. Morphological studies indicate that the adipose cell evolution could be nonidentical in BAT more or less enriched in essential fatty acids. Linoleic enriched BAT (of animals born to females kept on a sunflower oil diet) seemed to be in a healthy physiological state at birth, perhaps due to rapid lipid renewal and synthesis in their membranes. The control BAT (of animals born to females kept on a lard diet) appeared loaded with fats and in a worse conservation state at the same age.

Adipose Tissue, Brown↗
PubMed1979

Lipogenesis in human adipose tissue in vitro: effect of fat cell size on some enzymatic activities.

The incorporation of [1-C14] palmitate into palmitoyl CoA and triglycerides by homogenates of human adipose tissue have been studied. Adipose tissue samples were taken from three sites varying in adipocytes size (omentum, subcutaneous abdominal wall, buttock). The donors were normal weight women of constant weight. A significant positive correlation was found between initial velocity of palmitoyl CoA synthetase (EC 6.2.1.3) and total [1-C14] palmitate incorporation into triglycerides on one hand and adipocyte cell size on the other hand : these relations with cell size were apparent both within and between individuals. The mechanism of this "size effect" which is unrelated to the higher protein content of larger cells, is still unexplained. Lipogenesis, like most of the metabolic activities of adipose tissue increases with enlarging cell size. Acceleration of a lipogenesis-lipolysis cycle could constitute an energy wasting system able to limit the volume of the adipocytes.

Adipose Tissue↗
PubMed1979

Effects of 2,4-dihydroxybutyrate on lipogenesis in rat hepatocytes.

Hepatocytes were prepared from rats fasted 2 days and refed a high carbohydrate diet for 1 day. These cells contained very high levels of glycogen (about half the defatted dry weight) and carried out high rates of lipogenesis (up to 800 micron at tritium incorporation from 3HOH/g (defatted dry weight)/h), even in the absence of added substrates. Pentose cycle flux was estimated by a method involving the use of [1-14C]galactose (Rognstad, R. (1976) Int. J. Biochem. 7, 221-228). In hepatocytes from normal fasted refed rats, the amount of NADPH produced by the pentose cycle was sufficient for about one-half to three-fourths of that required for fatty acid synthesis. 2,4-Dihydroxybutyrate, a malic enzyme inhibitor (Schimerlik, M.I. & Cleland, W.W. (1977) Biochemistry 16, 565-570) markedly depressed the randomization of 14C in lactate from [6-14C]hexoses, indicating an inhibition of the pyruvate cycle. 2,4-Dihydroxybutyrate (10 mM) had only a slight inhibitory effect on overall lipogenesis, but increased the rate of the pentose cycle by 40 to 90%.

Animals↗
PubMed1979

Lipogenesis in vivo in lean and genetically obese (ob/ob) mice fed on diets with a high fat content.

The effect of variations in the fat content of the diet on fatty acid synthesis in vivo was determined in lean and genetically obese mice, using the 3H2O incorporation technique. In both lean and obese mice the rate of fatty acid synthesis was higher between 21.00 - 22.00 h than between 09.00 - 10.00 h. When lean mice were given a high fat (low-carbohydrate) diet the rate of lipogenesis in adipose tissue and rest of carcass (whole mouse minus liver and adipose tissue) was less than in similar mice given a high-carbohydrate (low-fat) diet. In obese mice, the rate of lipogenesis in adipose tissue and rest of carcass was unaffected, but liver fatty acid synthesis was reduced. In lean mice fed on diets containing a constant percentage of carbohydrate and protein, increasing the fat content of the diet (and decreasing the proportion of cellulose) produced a decrease in fatty acid synthesis in liver, adipose tissue and rest of carcass, when the measurements were made during the night-time feeding period. During the day-time, the effect of increasing the fat content of the diet was less marked. In obese mice, dietary fat did not supress either the day-time or the post-prandial night-time rate of fatty acid synthesis. It is suggested that the hyperinsulinaemia in obese mice may be able to overcome the inhibitory effect of dietary fat on fatty acid syntheses.

Adipose Tissue↗
PubMed1979

Lipogenesis in Ehrlich ascites tumor cells under anaerobic culture conditions.

Anaerobic culture conditions (95% argon/5% CO2) caused a slightly greater increase in total lipids of Ehrlich ascites tumor cells than a gas phase of 20% O2, 75% N2, 5% CO2. Whereas the rate of [U-14C]acetate incorporation into total lipids and lipid-subclasses rose markedly in the absence of oxygen, a drastic decrease of [U-14C]pyruvate and [1-14C]octanoate incorporation as well as a 30% reduction of 3H incorporation into lipids from tritiated water were observed under these conditions. Since profound changes in the metabolic state of cells cause alterations in the specific activity of the acetyl-CoA pool but do not alter the specific activity of intracellular water, this precursor is considered to be an adequate monitor for lipogenesis under aerobic and anaerobic culture conditions. Therefore, it is concluded that Ehrlich ascites tumor cells are not able to reoxidize NADH/NADPH in the absence of oxygen by a stimulation of biosynthesis of fatty acids as is discussed to be the case in normal cells. The slight increase in total lipids of anaerobically cultured cells seems to be the result of an imbalance between normal uptake and impaired utilization of lipids from serum-supplemented culture medium.

Anaerobiosis↗