Fatty Acid Synthetase Activity Research Articles

Possible relationship of succinate dehydrogenase and fatty acid synthetase activities toAspergillus parasiticus (NRRL 5139) growth and aflatoxin production

Fatty acid synthetase (FAS) activity measured over time corresponded to aflatoxin B1 biosynthesis by Aspergillus parasiticus grown in minimal salts sucrose medium. Succinate dehydrogenase (SDH) activity, our primary metabolism indicator, decreased as FAS activity increased demonstrating that as primary metabolism slows, secondary metabolism and subsequently aflatoxin production begins. Fungal biomass, as measured by chitin, increased up to day 13 then stabilized. Calcium, potassium, magnesium, manganese, zinc, and a combination of these minerals were tested to determine their effect in culture on FAS and SDH activities. Cultures grown in broth supplemented with zinc had greater FAS activity and produced more aflatoxin B1 when compared to the unsupplemented control. To determine if enzyme activity in a complex substrate is altered due to mineral composition, peanuts were cultivated with gypsum (calcium sulfate) supplementation. The peanuts grown had higher calcium content but less zinc. All peanuts grown in gypsum treated fields had less aflatoxin produced on them when compared to unsupplemented peanuts. Also, FAS activity was lower and chitin content was less when compared to the unsupplemented control peanuts. The FAS activity observed in these experiments indirectly suggests that the FAS complex may be responsible for producing the precursor for aflatoxin synthesis. However, additional information is needed to validate this hypothesis.

Metabolic Measurements among Homozygous (fa/fa) Obese, Heterozygous (Fa/fa) Lean and Homozygous (Fa/Fa) Lean Zucker Rat Pups at 17 Days of Age

AbstractFactors associated with the development of obesity were compared among obese (fa/fa), heterozygous (Fa/fa) lean and homozygous (Fa/Fa) lean Zucker rats at 17 d of age. Inguinal pad weight, pad-to-body weight ratio and fat cell size were highest in obese pups (fa/fa >Fa/fa >Fa/Fa). Hepatic glucose-6-phosphate dehydrogenase activity was greater in fa/fa than in Fa/Fa pups; 6-phosphogluconate dehydrogenase activity was higher in fa/fa and Fa/fa pups than in Fa/Fa pups, and fatty acid synthetase was greater in fa/fa compared with lean pups (Fa/fa = Fa/Fa). The fa/fa pups had greater adipose tissue glucose-6-phosphate dehydrogenase, malic enzyme and fatty acid synthetase activities than lean pups, which did not differ from one another (Fa/fa = Fa/Fa), whereas 6-phosphogluconate dehydrogenase and lipoprotein lipase activities were highest in obese pups, intermediate in heterozygotes and lowest in homozygous lean rats (fa/fa >Fa/fa >Fa/Fa). Glucose conversion to carbon dioxide and fatty acids in isolated adipocytes was highest in obese pups (fa/fa >Fa/fa >Fa/Fa). Glyceride-glycerol production was greater in Fa/Fa than in fa/fa or Fa/fa pups. These findings indicate that many characteristics of obesity are evident in preobese Zucker rats, and for some factors the presence of the “fa” gene in lean rats results in intermediate measurements relative to the two homozygous genotypes

Lipid composition and metabolism of subcutaneous fat in sheep divergently selected for carcass lean content

AbstractFatty acid synthetase and lipoprotein lipase activities, lipid content of adipose tissue and the fatty acid composition of subcutaneous fat, sampled by biopsy at the 13th rib, were measured in 20-week-old rams from lines of Texel-Oxford (TO) and Scottish Blackface (SB) sheep, both divergently selected for carcass lean content. A total of 150 animals were measured, with close to equal numbers of animals per selection line-breed combination.In both breeds, the high (lean) selection lines had significantly lower backfat depths (TO : 0·5 mm and SB : 0·6 mm, s.e.d. 0·2) than the low (fat) lines. The lipid content of subcutaneous fat was 65 mg lipid per g fat tissue wet weight (s.e.d. 24) greater in TO rams than in SB rams. The TO low line had a higher lipid content than the high selection line (426 v. 448 (s.e.d. 36)) and although the SB selection lines did not differ, the selection line with breed interaction was not significant. SB rams had higher fatty acid synthetase activity (3·1 v. 2·6 (s.e.d. 0·3) on a log scale) but there were no differences between selection lines. Lipoprotein lipase activities were similar between breeds and selection lines. The lower concentration of myristic acid (C14:0) of TO rams compared with SB rams (0·9 (s.e.d. 0·3)) was the only breed or selection line difference which was statistically significant for fatty acid composition of subcutaneous fat.Lipid content of subcutaneous fat and lipoprotein lipase activity were highly correlated and both were positively correlated with performance test traits, especially with backfat depth. The correlation between backfat depth and fatty acid synthetase activity was not different from zero. Performance test traits, lipid content of subcutaneous fat and lipoprotein lipase activity were positively correlated with the unsaturated fatty acids, with the exception of C18 :1 when correlations were negative.

Glycinebetaine stimulates, but NaCl inhibits, fatty acid biosynthesis in the moderately halophilic eubacterium HX

Total fatty acid synthetase (FAS) and cyclopropane fatty acid synthetase (CFAS) activities in cell-free lysates of the moderately-halophilic eubacterium HX, have been determined using radiolabelled malonyl-CoA and S-adenosylmethionine respectively as the precursor. The activities of FAS and CFAS were extremely low in vitro in 100 mM buffers, but were stimulated up to 100-fold by exogenous addition of the compatible-solute glycinebetaine to lysates; optimum activities of FAS and CFAS in vitro were obtained in 2–3 M concentrations of this compatible solute. In contrast, NaCl added to the lysate assay system was strongly inhibitory: CFAS was 97% inhibited by 1 M NaCl whereas FAS was less sensitive with 3 M NaCl giving 82% inhibition. When the culture medium salinity was raised from 1 to 3 M NaCl, the endogenous activity of CFAS measured in vitro in lysates without additional compatible solute was approximately doubled. This increase in CFAS activity is enough to account for the known increase in CFA content which occurs when culture medium salinity is raised, and the data are discussed in the context of the role of intracellular compatible solutes during haloadaptation of membrane lipid composition.

Monostearoylglycerol-starch complex: its digestibility and effects on glycemic and lipogenic responses.

We examined whether a modification of a starch into an alpha-amylase resistant form can lead to a reduction of postprandial glucose and insulin responses, and consequently to a change of lipid metabolism in liver and adipose tissue. For this purpose, a processed starch was prepared using a cornstarch (70% amylose and 30% amylopectin) and monoacylglycerol (monostearate; MS), forming monostearate-starch complex (MS-treated cornstarch). When we determined in vitro hydrolysis of MS-treated cornstarch using alpha-amylase and intestinal microvillar alpha-glucosidases, the glucose production rate of the MS-treated cornstarch was slower than the non-treated cornstarch. Measurement of a transmural potential difference (delta PD) evoked by the MS-treated cornstarch in everted rat jejunum showed that the absorption rate of glucose released from the MS-treated cornstarch was also remarkably slower than that from the non-treated cornstarch. The postprandial plasma insulin response to the MS-treated cornstarch was reduced, although plasma glucose response was unchanged. In a feeding study, two groups of five or six male Wistar-strain rats were fed defined diets containing 61.1% MS-treated cornstarch or 58.2% non-treated cornstarch ad libitum for 14 days. Food intakes during the period were similar between the two groups. Feeding the MS-treated cornstarch resulted in a significantly lower maltase activity in upper jejunum than did the non-treated cornstarch feeding. The activities of lipogenic enzymes--fatty acid synthetase (FAS), malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G-6-PDH)--significantly decreased in epididymal adipose tissue of rats fed the MS-treated cornstarch. In the liver, FAS activity was lower in the MS-treated cornstarch group. The results indicated that MS-treated cornstarch was digested less rapidly, and lowered blood insulin response, consequently leading to a declined lipogenesis of adipose tissue and liver. This study suggests that the rate of intestinal hydrolysis of starch is an important determinant of metabolic responses such as glycemic and lipogenic responses to diets.

Insulin stimulates hepatic lipogenesis in rainbow trout, Oncorhynchus mykiss

The effects of the pancreatic hormones, insulin and glucagon, on rates of lipid biosynthesis in liver removed from rainbow trout, Oncorhynchus mykiss, were evaluated in vitro. Livers were removed from animals fasted for 30-36h, cut into ca. 1 mm(3) pieces, and incubated in the presence of various concentrations of salmon insulin (sINS), bovine insulin (bINS), or a combination of BINS and bovine/porcine glucagon (GLU). Lipid synthesis was evaluated by total lipid concentration, (3)H2O incorporation into total lipid, and by fatty acid synthetase activity. Both mammalian and sINS tended to increase tissue total lipid concentration in hepatic tissue incubated for 5h. Insulin also stimulated (3)H2O incorporation into total lipid in a dose-dependent manner. Bovine INS (2 × 10(-6) M) stimulated de novo synthesis nearly 6-fold over control rates; sINS (2 × 10(-6) M) stimulated label incorporation more than 7-fold over control rates. Glucagon inhibited INS-stimulated (3)H2O incorporation; whereas, GLU alone had no effect on lipid synthesis in liver pieces incubated 5h. Lipid class analysis indicated that bINS significantly stimulated (3)H2O incorporation into phospholipids, fatty acids, and triacylglycerols. The greatest accumulation of label was in the triacylglycerol fraction, where incorporation was stimulated 17-fold over control levels. Hepatic enzymatic analysis indicated that bINS also significantly stimulated lipogenic enzyme activity 9-fold above control levels. These results indicate that INS is an important regulator of lipid synthesis in the liver of trout.

Estrogens and antiestrogens: actions and interactions with fluphenazine on food intake and body weight in rats.

Treatment of ovariectomized rats for 3 days with 2 micrograms estradiol benzoate (E2B), 6 micrograms ethinyl estradiol, or 1-2 mg of either of the antiestrogens nafoxidine or tamoxifen led to similar decreases in food intake, body weight gain, adipose tissue lipoprotein lipase activity, and hepatic fatty acid synthetase activity, despite their different effects on uterine growth and induction of progestin receptors in pituitary and adipose tissue. Longer-term (2 wk) treatment with tamoxifen resulted in similar transient changes in food intake and body weight gain, as did treatment with E2B. Daily administration of 50 micrograms fluphenazine (FLU) led to significant decreases in body weight, although there was no change in food intake. Concurrent administration of FLU with either E2B or tamoxifen led to additive effects on body weight and food intake change. None of the treatments had any effect on in vitro binding of [3H]tamoxifen to antiestrogen binding sites in pooled hypothalamic-preoptic area samples.

Methyl-branched fatty acid biosynthesis in the German cockroach, Blatella germanica: Kinetic studies comparing a microsomal and soluble fatty acid synthetase

The fatty acid synthetase (FAS) activity of integument-enriched tissue from the German cockroach, Blatella germanica, was separated into soluble and microsomal forms. Both the soluble and microsomal FAS incorporated methylmalonyl-CoA into fatty acids, but their kinetic characteristics were quite different. The specific activity for soluble FAS was 144 ± 7 nmol NADPH oxidized/min/mg protein and for microsomal FAS it was 20 ± 1 nmol/min/mg. Both have similar Michaelis constants. There was a clear-cut substrate preference: the soluble FAS had almost no activity with methylmalonyl-CoA as the only elongating substrate whereas the microsomal FAS readily utilized methylmalonyl-CoA in the absence of malonyl-CoA. The specific activity with methylmalonyl-CoA for the microsomal FAS was 7 ± 1 nmol/min/mg. Methylmalonyl-CoA was a competitive inhibitor against malonyl-CoA for both the soluble and microsomal FAS, which indicated that methylmalonyl-CoA can bind to both forms of the enzyme. Methylmalonyl-CoA was a non-competitive inhibitor against acetyl-CoA for both the soluble and microsomal FAS. In the presence of malonyl-CoA, the microsomal FAS had a much higher ability to incorporate methylmalonyl-CoA into fatty acid than did the soluble FAS. The data indicated that the microsomal FAS from integument tissue plays a key role in methyl-branched fatty acid synthesis by incorporating methylmalonyl-CoA into growing fatty acid chains.

Effects of brazilin on glucose oxidation, lipogenesis and therein involved enzymes in adipose tissues from diabetic KK-mice

In order to address the hypoglycemic mechanism of brazilin, effects on glucose metabolism in epididymal adipose tissue from diabetic KK-mice were investigated. Brazilin remarkably lowered non fasting plasma glucose level without any changes in plasma insulin level. Brazilin significantly increased the rate of glucose oxidation and lipogenesis only in the presence of insulin. Activities of glucose-6 phosphate dehydrogenase and fatty acid synthetase, involved in glucose oxidation and lipogenesis respectively, were significantly increased. These results suggest that brazilin might exert hypoglycemic action in insulin resistance state by, at least in part, regulating the enzymatic reaction process involved in glucose metabolism.

Effects of pantethine on lipogenesis and CO 2 production in the isolated hepatocytes of the chick ( Gallus domesticus)

1. 1. Isolated hepatocytes from chicks were used to study the effects of pantethine supplementation to incubation medium on in vitro lipogenesis, CO 2 production and β-oxidation of fatty acid. 2. 2. In vitro lipogenesis, determined by the incorporation of 1-[ 14C]acetate into total lipid and various lipid fractions, as depressed in concordance with the increase of pantethine concentration in the medium. 3. 3. Incubation of isolated hepatocytes with pantethine resulted in a significant decrease ( P < 0.01) in the activities of acetyl-CoA carboxylase and fatty acid synthetase. 4. 4. The results suggest that in vitro fatty acid synthesis from l-[ 14C]aeetate was depressed and CO 2 production was elevated in hepatocytes of chicks through pantethine addition to the medium at a low level.

Synthesis in vitro of very long chain fatty acids in Vibrio sp. strain ABE-1.

The activity of fatty acid synthetase (FAS) from Vibrio sp. strain ABE-1 required the presence of acyl carrier protein and was completely inhibited by thiolactomycin, an inhibitor specific for a type II FAS. These observations indicate that this enzyme is a type II FAS. Analysis by gas-liquid chromatography of the reaction products synthesized in vitro from [2-14C]malonyl-CoA by the partially purified FAS revealed, in addition to 16- and 18-carbon fatty acids which are normal constituents of this bacterium, the presence of fatty acids with very long chains. These fatty acids were identified as saturated and mono-unsaturated fatty acids with 20 up to as many as 30 carbon atoms. The longest fatty acids normally found in this bacterium contain 18-carbon atoms. These results suggest that the FAS from Vibrio sp. strain ABE-1 has potentially the ability to synthesize fatty acids with very long chains.

Effect of the peroxisome proliferator LY171883 on triglyceride accumulation in rats fed a fat-free diet

LY171883 is a leukotriene D 4 antagonist that induces peroxisome proliferation in the rodent liver. Like many peroxisome-proliferating agents, it causes transient lipid accumulation and several other changes in hepatic lipid metabolism. The effect of LY171883 on lipid metabolism was studied further in rats maintained on a fat-free diet. Administration of a fat-free diet for 14 days caused a 5.6-fold increase in liver triglycerides associated with a 3.3-fold increase in fatty acid synthetase. Co-administration of 0.1% LY171883 increased liver triglycerides slightly, whereas 0.3% LY171883 prevented the accumulation of triglycerides. Furthermore, treatment with 0.3% LY171883 reversed the fatty liver in rats pretreated with the fat-free diet for 14 days. Fatty acid synthetase activity increased comparably in all treatment groups, indicating that 0.3% LY171883 did not prevent the lipogenic response to a fat-free diet. In rats treated with 0.3% LY171883, peroxisomal β-oxidation increased 9.5-fold, mitochondrial β-oxidation 4.8-fold, carnitine palmitoyltransferase I 1.9-fold, and plasma ketones 3-fold. In the 0.1% dose group the increases in these parameters were smaller. The data indicate that 0.3% LY171883 sufficiently increased mitochondrial and peroxisomal β-oxidation such that fatty acids generated by lipogenesis were preferentially oxidized rather than esterified to triglycerides. In the 0.1% dose group oxidation was only mildly increased, and the excess fatty acids continued to be esterified.

Duodenal Rapeseed Oil Infusion in Early and Midlactation Cows. 5. Milk Fatty Acids and Adipose Tissue Lipogenic Activities

Lipogenic activities of perirenal adipose tissue were investigated in early (wk 3) and midlactation (wk 19 to 26) cows that received a duodenal rapeseed oil infusion (1.0 to 1.1 kg/d). In midlactation, oil infusion resulted in a decreased rate of fatty acid synthesis from acetate and a decreased rate of the activities of fatty acid synthetase and glucose-6-phosphate dehydrogenase, whereas lipoprotein lipase activity tended to increase. The rate of glucose incorporation into glyceride-glycerol and the activities of glycerol-3-phosphate dehydrogenase and malic enzyme were not significantly affected. Fatty acid C14:0 content of perirenal adipose tissue was decreased, and fatty acid C18:2 and C18:3 contents were increased in oil-infused cows. In early lactation, rates of acetate incorporation into fatty acids and activities of fatty acid synthetase and lipoprotein lipase were very low. Activities of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase were lower in the early than in the midlactation trial. Oil infusion did not change the measured parameters. In both trials, percentages and yields of milk fatty acids C18:1, C18:2, and C18:3 were increased, whereas those of C14:0. and C16:0 were decreased by oil. Calculated transfer rates of absorbed fatty acid C18:2 from oil to milk fat were 16 to 26%. Results suggested that oil fatty acids affected adipose and mammary de novo lipogenesis in a direct way without affecting fatty acid esterification in adipose tissue or total fat secretion in mammary tissue.

Differentiation of Type II Cells during Explant Culture of Human Fetal Lung Is Accelerated by Endogenous Prostanoids and Adenosine 3′,5′-Monophosphate*

Explant culture of the fetal lung, in the absence of serum or hormones, results in precocious biochemical and morphological differentiation of alveolar epithelial cells. In this study we tested the hypothesis that these maturational events are induced by endogenous cAMP. During culture of human fetal lung the content of tissue cAMP increased 140% from days 3-6. Treatment with isobutylmethylxanthine caused a further doubling of cAMP content, and indomethacin blocked most of the increase in cAMP. Isobutylmethylxanthine accelerated and indomethacin inhibited the increases during culture in surfactant protein-A (SP-A), SP-A mRNA, SP-B mRNA, phosphatidylcholine content, and activity of fatty acid synthetase. There was no effect of these treatments on the content of SP-C mRNA, which did not increase during culture. Increasing concentrations of prostaglandins E1 and E2 in the presence of indomethacin produced a parallel stimulation of cAMP content, SP-A, and fatty acid synthetase activity. The temporal increase in SP-A was also blocked by inhibitors of protein kinase-A. In morphological studies, indomethacin-treated explants appeared less mature, with decreased intralumenal volume and more columnar epithelial cells. We conclude that increased tissue cAMP levels, stimulated by endogenous prostaglandins, accelerate differentiation of alveolar epithelial cells during explant culture.

Regulation of mouse mammary cell differentiation by extracellular milk proteins

Differentiation of mammary epithelial cells prepared from pregnant mice was stimulated by culture on floating collagen gels in the presence of lactogenic hormones. Differentiation was measured by the induction of casein synthesis and fatty acid synthase activity, both of which increased by up to 15-fold during 12 days of culture. Addition of a 10-30 kDa fraction of goat whey proteins to culture medium from day 3 inhibited casein synthesis by greater than 20% compared with control cultures on days 4-12, and prevented further induction of fatty acid synthetase activity. Inhibition of secretory cell differentiation by this fraction, which is known to inhibit milk synthesis acutely in explant culture and lactating goats, suggests that similar autocrine mechanisms may mediate the sequential local effects on milk yield and cell differentiation elicited by manipulation of milking frequency or efficiency.

Fattening and fatty acid synthetase in juvenile richardson's ground squirrels

1. 1. Intraperitoneal white adipose tissue (WAT) first appeared in juvenile squirrels when they were 10–12 weeks old and had achieved about two thirds of adult lean body mass. 2. 2. Rate of fat deposition at age 12–16 weeks was about 6.5 g per week, similar to the rate in adults during their respective periods of prehibernatory fattening when expressed as fat deposited per 100 g of lean body mass. 3. 3. Upon emergence from the natal burrow there was little fatty acid synthetase (FAS) activity and most of that was in liver. At 14 weeks of age nearly all FAS activity was in WAT, suggesting WAT was the primary tissue of fatty acid synthesis. 4. 4. At a given age, there were no differences between sexes in FAS activity of liver, WAT, or brown adipose tissue (BAT).

The Effect of Feather Meal on Carcass Composition and Fat Pad Cellularity in Broilers: Influence of the Calorie:Protein Ratio of the Diet

An experiment with a factorial arrangement of treatments was designed to study the effects of feather meal (FM) and the calorie:protein ratio (C:P) of the finisher diet on growth, carcass composition, and the cellular characteristics of the abdominal fat pad in broiler chickens. Four finisher diets were formulated to contain either 0 or 6% FM in combination with C:P of 161 and 186. The diets were available for ad libitum consumption from 35 to 49 days of age.Growth was unaffected by dietary FM at C:P 161 but was reduced at C:P 186, thus indicating a metabolic interaction between the FM and C:P and growth. The FM and C:P 186 each increased carcass yield significantly. Abdominal fat pad weight was not affected by the dietary treatments. Carcass analysis revealed a significant interaction between dietary FM and C:P and carcass weight, protein, and fat. The interaction was manifested as an increase in carcass weight and protein when FM was fed at C:P 161 but a decrease at C:P 186. The change in carcass fat was opposite that of protein at each C:P level. Liver fatty acid synthetase activity was depressed by the feeding of FM. Fat cell number and mean fat cell size were unaffected by either FM feeding or C:P level. These data suggest that dietary FM improves carcass yield and carcass composition, but that the response to dietary FM is influenced by the C:P ratio of the diet.

β-Adrenergic Receptors and cAMP Response Increase during Explant Culture of Human Fetal Lung: Partial Inhibition by Dexamethasone

We studied beta-adrenergic receptors and responses in human fetal lung (15-25 wk gestation) maintained in explant culture with and without added dexamethasone. To determine beta-adrenergic receptor concentration, we performed radioligand binding assays with [125I]-iodocyanopindolol. We also examined the ability of isoproterenol to stimulate cAMP generation as a measure of response to beta-adrenergic receptor occupancy. In control cultures, beta-receptor concentration increased significantly from d 0 to 3 of culture and thereafter remained stable. The kd (approximately 24 pM) of [125I]-iodocyanopindolol did not change with time in culture. The ability of isoproterenol to stimulate cAMP generation over basal levels increased in controls throughout the 5 d in explant culture. Addition of dexamethasone (10 nM) to the culture medium partially blocked the increase in beta-receptor concentration and decreased both cAMP content and generation (basal and stimulated) in a dose-dependent manner (median effective concentration approximately 1 nM). In these same explants, dexamethasone increased the activity of fatty acid synthetase, an enzyme important in surfactant synthesis, more than 2-fold. Our results indicate that beta-adrenergic receptors and isoproterenol stimulation of cAMP generation increase spontaneously in human fetal lung grown in explant culture. Dexamethasone, which accelerates other aspects of human lung development in vitro, decreases beta-adrenergic receptor concentration and inhibits beta-adrenergic responses.

Acyl carrier protein interacts with melittin

Acyl carrier protein (ACP) from Escherichia coli has been shown to form complexes with melittin, a cationic peptide from bee venom. ACP is a small ( M r 8847), acidic, Ca 2+-binding protein, which possesses some characteristics resembling those of regulatory Ca 2+-binding proteins including interaction with melittin. Complexing between melittin and ACP which occurred both in the presence and absence of Ca 2+ was evident by chemical cross-linking the two peptides, fluorescence changes (including anisotropy measurements), and inhibition by melittin of the activity of a nonaggregated fatty acid synthetase from Euglena. Also, anti-Apis mellifera antibodies which contained antibodies against melittin specifically inhibited the same enzyme system activity relative to non-immune IgG.

Metabolic changes in rats fed a low protein diet during post-weaning growth

Metabolic changes in rats fed a low protein diet were investigated during 3 weeks after weaning using lactalbumin (LP) as dietary protein source. The energy intake was higher and the weight gain lower in rats fed the low protein diet (6%, LP group) than in control rats (13% lactalbumin, C group). Low protein diet induced no changes in plasma glucose, free fatty acids, or triacylglycerol concentrations; however, plasma protein and urea concentrations were lower in LP than in C rats. Plasma free T 3 was higher in LP than in C rats (+38%, day 21) and insulin progressively decreased during the experimental period (−56%, day 21) without change in glucagon. Liver glycogen and triacylglycerol concentrations (+40% and + 180%, respectively, day 21), and cytosolic and mitochondrial redox states increased (+100% and +100%, day 21), and protein concentration was decreased (−15%, day 21). Pyruvate kinase (PK) and malic enzyme activities were higher in LP than in C rats throughout the experiment (+80% and +210%, respectively, day 21), and glucose-6-phosphate dehydrogenase (G6PDH) activity progressively decreased (−65%, day 21). Phosphoenolpyruvate carboxykinase (PEPCK) activity increased after 2 weeks on a LP diet (+35%, day 21) and fatty acid synthetase (FAS) activity increased only during the first week on the diet (+100%, day 7). Such hormonal and metabolic changes appeared to be associated with the development of a futile energy-wasting cycle between pyruvate and phosphoenolpyruvate.