Hepatic acetyl-CoA Carboxylase Activity Research Articles

Dietary Medium-Chain Fatty Acids Raise and (n-3) Polyunsaturated Fatty Acids Lower Hepatic Triacylglycerol Synthesis in Rats

The hypothesis tested was that dietary medium-chain or (n-3) polyunsaturated fatty acids, when compared with (n-6) polyunsaturated fatty acids, alter plasma triacylglycerol levels by affecting hepatic triacylglycerol synthesis as reflected by the activities of acetyl-CoA carboxylase, fatty acid synthase and diacylglycerol acyltransferase in liver. In two separate experiments rats were fed purified diets containing (n-6) polyunsaturated fatty acids in the form of corn oil and either (n-3) polyunsaturated fatty acids in the form of fish oil or medium-chain triacylglycerols (MCT). Consumption of MCT significantly raised plasma triacylglycerol concentrations, whereas fish oil feeding had a lowering effect compared with the corn oil-fed group. In individual rats, the hepatic triacylglycerol concentration was directly correlated with the plasma triacylglycerol concentration (r = 0.60, P < 0.001). The MCT oil diet vs. the corn oil diet markedly raised the activities of hepatic acetyl-CoA carboxylase, fatty acid synthase and diacylglycerol acyltransferase. In the rats fed fish oil, the activities of fatty acid synthase and diacylglycerol acyltransferase were significantly reduced, whereas the activity of acetyl-CoA carboxylase was not affected relative to activities in rats fed corn oil. The activities of the three enzymes were directly correlated with plasma triacylglycerol concentrations in individual rats (r = 0.60–0.75, P < 0.001). The type of fat in the diet probably affects the rate of hepatic triacylglycerol synthesis which is an important determinant of plasma triacylglycerol concentrations.

Age-Related Changes in Serum Lipid Levels, Hepatic Morphology, Antioxidant Status, Lipid Metabolism Related Gene Expression and Enzyme Activities of Domestic Pigeon Squabs (Columba livia).

Simple SummaryResearch on antioxidant status and lipid metabolism in pigeon squabs as meat type poultry is limited. The objective of this study was to explore the age-related changes in the antioxidant status and lipid metabolism of pigeon squabs (Columba livia). Ten squabs were randomly selected, out of 400 hatched squabs, on the following days: day of hatching (DOH) and days 7 (D7), 14 (D14), 21 (D21) post-hatch, respectively. BW, serum lipid levels, antioxidant capacity indices, lipid metabolism-related enzyme activities, lipid metabolism-related gene expression, and liver morphology were determined. Results indicated that the phase from DOH to D14 was a growth spurt, especially in the first seven days. The antioxidant capacity of squabs had a continuous decline from DOH to D14. Besides, changes regarding lipid metabolism mainly occurred in the phase from DOH to D14. The first seven days mainly showed less lipid breakdown, while the second seven days displayed more complicated lipid metabolism. The results obtained from this study suggested that, in the pigeon industry, it is better to take nutritional manipulation in squabs before D14.The objective of this study was to evaluate the age-related changes in antioxidant status and the lipid metabolism of pigeon squabs (Columba livia), by determining the BW, antioxidant indices, serum lipid levels, lipid metabolism-related enzyme activities, lipid metabolism-related gene expression, and liver morphology in squabs. Ten squabs were randomly selected and sampled on the day of hatching (DOH), days 7 (D7), 14 (D14) and 21 (D21) post-hatch, respectively. The results showed that BW of squabs increased linearly from DOH to D21. The minimum fold of BW gain was observed in the phase from D14 to D21. Serum triglyceride and free fatty acid levels displayed linear and quadratic trends as age increased, with these maximum responses in D14. Serum low-density lipoprotein cholesterol level responded to age linearly and quadratically with the minimum in D14. Serum high-density lipoprotein cholesterol level and the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol increased linearly with age, whereas the very low-density lipoprotein cholesterol level decreased linearly. The activities of glutathione peroxidase, catalase, and superoxide dismutase in liver displayed linear and quadratic trends as age increased, with these minimum responses in D14. Hepatic malondialdehyde concentration responded to age linearly and quadratically, with the maximum in D14. Activities of lipoprotein lipase, hepatic lipase, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver responded to age linearly and quadratically, with these minimum responses in D14. Hepatic hormone-sensitive lipase activity displayed linear and quadratic trends as age increased with the maximum in D14. Hepatic acetyl CoA carboxylase activity on D14 was significantly lower than squabs on DOH and D7. Hepatic carnitine palmitoyltransferase 1 mRNA expression responded to age linearly and quadratically, with minimum response in D14. Hepatic mRNA expression of acetyl CoA carboxylase and fatty acid synthetase increased linearly with age. Hepatic Oil-Red-O staining area displayed a quadratic trend as age increased, with the maximum response in D14. In conclusion, the phase from DOH to D14 was a crucial development stage for growth, antioxidant status and lipid metabolism in pigeon squabs. The results suggest it is better to take nutritional manipulation in squabs before D14.

Ganoderma lucidum culture supplement ameliorates dyslipidemia and reduces visceral fat accumulation in type 2 diabetic rats

ABSTRACT Diabetic rats were daily fed with a high-cholesterol diet containing 1% or 3% freeze-dried whole submerged G. lucidum culture or its mycelia for 5 weeks. Body weight, adipose tissue weight and plasma triglyceride levels were reduced, while high-density lipoprotein-cholesterol levels were elevated in rats fed with G. lucidum powder supplement diets. Notably, G. lucidum supplements downregulated the activities of hepatic acetyl-CoA carboxylase, fatty acid synthase and lipoprotein lipase, but upregulated the activity of hormone-sensitive lipase in the perirenal adipose tissues. Moreover, G. lucidum supplements increased the faecal triglyceride excretion. Therefore, daily supplementation of submerged G. lucidum culture, especially mycelia, can ameliorate dyslipidemia and reduce visceral fat accumulation in diabetic rats fed with a high-fat diet, which is closely related to the modulation of lipid synthesis, metabolism, and excretion.

Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats

Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis.

Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylation.

Lipid deposition in the liver is associated with metabolic disorders including fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat storage; therefore, their inhibition is expected to prevent the development of fatty liver. In this study we generated liver-specific ACC1 and ACC2 double knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat metabolism and whole-body physiology. Characterization of LDKO mice revealed unexpected phenotypes of increased hepatic triglyceride and decreased fat oxidation. We also observed that chronic ACC inhibition led to hyper-acetylation of proteins in the extra-mitochondrial space. In sum, these data reveal the existence of a compensatory pathway that protects hepatic fat stores when ACC enzymes are inhibited. Furthermore, we identified an important role for ACC enzymes in the regulation of protein acetylation in the extra-mitochondrial space.

약용식물 물 추출물이 Goto-Kakizaki 흰쥐의 간 세포액에서 당대사 관련효소 활성에 미치는 영향

본 연구에서는 유전적으로 제2형 당뇨를 가진 Goto-Kakizaki 흰쥐의 간 세포액에 함유된 당 이용 대사 관련 주요 효소인 glucokinase(GK)와 acetyl CoA carboxylase(ACC)에 약용 식물 물 추출물들이 어떤 영향을 미치는지 알아보았다. α-Glucosidase 저해제는 제2형 당뇨 치료와 예방을 위해 사용되어져 오고 있다. 따라서 약용식물 물 추출물들의 α-glucosidase 저해 활성을 알아보았다. Goto-Kakizaki 흰쥐의 간 세포액 분획물을 GK과 ACC 활성을 알아보기 위해 사용하였다. 본 실험에 사용된 약용 식물들은 Lycium chinense(JGP), Discorea japonica Thunb.(SY), Pyrus pyrifolia(YSB), Cornus officinalis(SSY), Paeonia suffruticosa ANDR.(MDP), Cordyceps militaris(DCH) 그리고 Acanthopanax senticosus(GSO)였다. 지골피(JGP), 산약(SY), 야생배(YSB) 그리고 산수유(SSY) 물 추출물들은 GK 활성을 증가시켰고, 실험에 사용된 모든 약용식물 물 추출물들은 간 ACC 활성을 증가시켰다. 야생배(YSB), 산수유(SSY), 목단피(MDP) 그리고 가시오가피(GSO) 물 추출물들은 대조군보다 현저히 높은 α-glucosidase 활성 억제를 보여주었다. α-Glucosidase 활성을 가장 억제시킨 것은 GSO 물 추출물이었고, 그 억제율은 α-glucosidase 치료제인 acarbose보다 높았다. 따라서 제2형 당뇨에서 지골피(JGP), 산약(SY), 야생배(YSB) 그리고 산수유(SSY) 물 추출물들은 글루코스 대사과정을 활성화시켜 항당뇨 효과를 나타내는 천연 소재일 것으로 생각되고 야생배(YBS), 목단피(MDP) 그리고 가시오가피(GSO)는 천연 α-glucosidase 저해제로써 사용될 수 있을 것이다. 약용식물 물 추출물에 의한 증가된 ACC 활성은 더해진 항당뇨 효과를 나타낼 것이다.

Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

Parenteral multivitamin preparation (MVP) induces fatty liver in neonatal guinea pig pups; this is prevented by photoprotection. Photo-excited riboflavin present in MVP generates H(2)O(2) and molecules with masses of 136 and 208. We hypothesized that H(2)O(2) initiates the peroxidation of ascorbic acid (AA), producing biologically active byproducts affecting hepatic lipid metabolism. Mass spectrometry (MS) documented the participation of H(2)O(2) and photo-excited riboflavin (Ribo) in the formation of AA byproducts. Sixteen 3-day-old guinea pig pups received an intravenous solution (50 g/L dextrose + 4.5 g/L NaCl + 1 kIU/L heparin) at 240 mL x kg(-1) x day(-1), enriched with control or test mixtures, for 4 days. The control mixture was photo-protected AA + Ribo (without byproducts or H(2)O(2)), and the test mixture was AA + Ribo treated to generate AA byproducts without H(2)O(2). Hepatic acetyl-CoA carboxylase (ACC) activity was determined after 4 days. Fourth-day urine samples were analyzed by MS. Data were treated by ANOVA (alpha = 0.05). H(2)O(2) did not influence the classic degradation of AA, as the generation of 2,3-diketogulonic acid was not affected. In contrast, the formation of molecules with masses of 136 and 208 was H(2)O(2) and time dependent. ACC activity was higher (P <0.01) in animals receiving high concentration of these molecules; its hepatic activation correlated (P <0.01) with the urinary concentration of molecule-208. H(2)O(2) at concentrations found in the clinical setting of total parenteral nutrition induce the transformation of dehydroascorbic acid into compounds that have the potential to affect lipid metabolism. These molecules have peroxide and aldehyde functions.

MEDICA 16 inhibits hepatic acetyl-CoA carboxylase and reduces plasma triacylglycerol levels in insulin-resistant JCR: LA-cp rats.

Intracellular triacylglycerol (TG) content of liver and skeletal muscle contributes to insulin resistance, and a significant correlation exists between TG content and the development of insulin resistance. Because acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme for liver fatty acid biosynthesis and a key regulator of muscle fatty acid oxidation, we examined whether ACC plays a role in the accumulation of intracellular TG. We also determined the potential role of 5'-AMP-activated protein kinase (AMPK) in this process, since it can phosphorylate and inhibit ACC activity in both liver and muscle. TG content, ACC, and AMPK were examined in the liver and skeletal muscle of insulin-resistant JCR:LA-cp rats during the time frame when insulin resistance develops. At 12 weeks of age, there was a threefold elevation in liver TG content and a sevenfold elevation in skeletal muscle TG content. Hepatic ACC activity was significantly elevated in 12-week-old JCR:LA-cp rats compared with lean age-matched controls (8.75 +/- 0.53 vs. 3.30 +/- 0.18 nmol. min(-1). mg(-1), respectively), even though AMPK activity was also increased. The observed increase in hepatic ACC activity was accompanied by a 300% increase in ACC protein expression. There were no significant differences in ACC activity, ACC protein expression, or AMPK activity in the skeletal muscle of the 12-week JCR:LA-cp rats. Treatment of 12-week JCR:LA-cp rats with MEDICA 16 (an ATP-citrate lyase inhibitor) resulted in a decrease in hepatic ACC and AMPK activities, but had no effect on skeletal muscle ACC and AMPK. Our data suggest that alterations in ACC or AMPK activity in muscle do not contribute to the development of insulin resistance. However, increased liver ACC activity in the JCR:LA-cp rat appears to contribute to the development of lipid abnormalities, although this increase does not appear to occur secondary to a decrease in AMPK activity.

13C NMR study of the effects of leptin treatment on kinetics of hepatic intermediary metabolism.

The recent discovery of leptin receptors in peripheral tissue raises questions about which of leptin's biological actions arise from direct effects of the hormone on extraneural tissues and what intracellular mechanisms are responsible for leptin's effects on carbohydrate and lipid metabolism. The present study is focused on the action of leptin on hepatic metabolism. Nondestructive 13C NMR methodology was used to follow the kinetics of intermediary metabolism by monitoring flux of 13C-labeled substrate through several multistep pathways. In perfused liver from either ob/ob or lean mice, we found that acute treatment with leptin in vitro modulates pathways controlling carbohydrate flux into 13C-labeled glycogen, thereby rapidly enhancing synthesis by an insulin-independent mechanism. Acute treatment of ob/ob liver also caused a rapid stimulation of long-chain fatty acid synthesis from 13C-labeled acetyl-CoA by the de novo synthesis route. Chronic leptin treatment in vivo induced homeostatic changes that resulted in a tripling of the rate of glycogen synthesis via the gluconeogenic pathway from [2-13C]pyruvate in ob/ob mouse liver perfused in the absence of the hormone. Consistent with the 13C NMR results, leptin treatment of the ob/ob mouse in vivo resulted in significantly increased hepatic glycogen synthase activity. Chronic treatment with leptin in vivo exerted the opposite effect of acute treatment in vitro and markedly decreased hepatic de novo synthesis of fatty acids in ob/ob mouse liver. In agreement with the 13C NMR findings, activities of hepatic acetyl-CoA carboxylase and fatty acid synthase were significantly reduced by chronic treatment of the ob/ob mouse with leptin. Our data represent a demonstration of direct effects of leptin in the regulation of metabolism in the intact functioning liver.

Chemical Sympathectomy Increases Hepatic Acetyl-CoA Carboxylase Activity in Rats Fed a Safflower Oil Diet.

We previously reported that the feeding of the safflower oil diet results in lower acetyl-CoA carboxylase activity in the liver compared with the feeding of a beef tallow diet. We also suggested that sympathetic activity (norepinephrine turnover rate and α1-adrenergic receptor binding) in the liver was higher in the safflower oil diet group. In order to confirm the effect of dietary fats consisting of different fatty acids on the hepatic acetyl-CoA carboxylase activity related to sympathetic activity, we chemically sympathectomized rats by treating them with 6-hydroxydopamine. The sympathectomized rats and control rats were then meal-fed a safflower oil diet or a beef tallow diet for 8 weeks. Sympathectomy abolished the difference in acetyl-CoA carboxylase activity in the liver between the two dietary groups. The percentage of body fat was increased by sympathectomy, resulting in no difference between the safflower oil diet group and the beef tallow diet group. These results support the hypothesis that, the intake of a safflower oil diet decreases hepatic acetyl-CoA carboxylase activity by increasing the sympathetic activity.

Safflower Oil Diet Decreases Hepatic Acetyl CoA-Carboxylase Activity by Increasing .ALPHA.1-Adrenergic Stimulation in Rats.

Effects of dietary fats consisting of different fatty acids on the acetyl CoA-carboxylase activity in liver was studied in rats. Sprague-Dawley male rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for 8 weeks. The acetyl CoA-carboxylase activity in liver was lower in the safflower oil diet group than in the beef tallow diet group. Body fat accumulation was less in rats fed the safflower oil diet, however, their norepinephrine turnover rate in liver was higher. α1-Adrenergic receptor binding was determined with [3H] prazosin. Binding affinity of α1-adrenergic receptor in liver was higher in the safflower oil diet group, presumably resulting from higher membrane fluidity in that group. These results suggest that the intake of the safflower oil diet promoted less body fat accumulation by reducing the acetyl CoA-carboxylase activity, which may be a result of higher sympathetic nervous system activity in the liver.

Alterations in acetyl coenzyme A carboxylase activities in voles and mice treated with monosodium aspartate.

Changes of body weights and hepatic acetyl-CoA carboxylase activities were measured in voles and mice treated with monosodium-L-aspartate (MSA). MSA was administrated subcutaneously to neonates at 4 mg/g. The MSA-treated mice showed remarkable obesity, associated with the increase in the plasma insulin concentrations and acetyl-CoA carboxylase activities. The activity of acetyl-CoA carboxylase of control voles was very low; under half that of mice. In the MSA-treated voles, although the plasma insulin concentrations also increased, acetyl-CoA carboxylase activities were not elevated and signs of obesity were not observed.

Depletion of hepatic coenzyme A derivatives is one of the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat.

When 400 mg/rat/day of secondary autoxidation products of linoleic acid was orally administered 3 times to rats, they died at 30-40 h after the third dose. To search the markers of the toxicity of secondary products in vivo, the rats were killed at 24h after the third dose, and conditions of their digestive tracts and liver were analyzed. In the stomach, macroscopically, inflation, retention of undigested food, and edema were seen. Slight congestions were detected in the small intestines. It was considered that these injuries led to reduction in food consumption and then depression of the growth, but did not lead to the death of the animals. The lipid peroxide levels in the liver and the activities of its detoxifying enzymes were increased as compared to those in the control groups. The hepatic lipid contents and unsaturated fatty acid compositions were also not changed. The endogenous lipid peroxidation, therefore, did not give the rats a severe stress. The activities of hepatic acetyl-CoA carboxylase and carnitine palmitoyltransferase were 20 and 35% lower than those of control, respectively. The levels of CoASH, acetyl-CoA, and long-chain acyl-CoA were 1/9, 1/2, and 1/4 of those in control, respectively. Thus, one of the markers of the toxicity of secondary products was the depletion of hepatic CoA derivatives. In rat, bio-energy was reduced by the decrease in the intestinal absorption of nutrients, and the depletion of hepatic CoA derivatives also failed to supply energy with beta-oxidation.

Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat.

Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats.

Metabolic effects of medium- or long-chain triglycerides and high-protein, carbohydrate-free diets in Zucker rats

The effects of protein levels and types of fat in the diet on the metabolism of lean and obese Zucker rats were studied. For 40 days the rats were fed ad libitum one of four diets: two “usual protein” diets (19% protein by weight) with 19.4% triacylglycerols, either long chain (UP-LCT diet) or medium chain (UP-MCT diet); and two high protein (64% protein), carbohydrate-free diets, again with 19.4% triacylglycerols (HP-LCT and HP-MCT diets, respectively). The energy intakes of the obese rats decreased about equally on the HP-LCT, UP-MCT, and HP-MCT diets. The daily weight gain, which was high in the UP-LCT rats, was lower when carbohydrates were replaced by proteins, or when LCTs were replaced by MCTs; furthermore, when these two changes were made together, their beneficial effects on body weight were additive. The lipid gain, too, was high with the UP-LCT diet and lower both with the high protein diets and with the MCT diets; again combining the two amplified the two individual effects, so much that the final lipid concentration in the body was lowered, whereas the concentration of water increased. Hepatic acetyl CoA carboxylase activity was low when the diet supplied plenty of LCTs, but replacing carbohydrates with proteins in such a diet produced an additional decrease in this enzymatic activity. When either a normal protein or a high protein diet supplied MCTs in place of LCTs, acetyl CoA carboxylase activity was high and similar to that found with a high carbohydrate diet. In the lean rats, the high protein diet overall had a greater effect on the parameters studied than did the MCT-based diet. The HP-MCT diet had no additional effect, except that it permitted the animals to gain a little weight, which, as we have seen, 1 is not the case with a high protein, carbohydrate-free, low fat diet.

Putative mediators of insulin action regulate hepatic acetyl CoA carboxylase activity

Incubation of rat liver plasma membranes with insulin enhances the production of small molecular weight substances which regulate the activity of liver acetyl CoA carboxylase. While low concentrations of insulin cause the release of a carboxylase stimulator from membranes, concentrations greater than 10 −9 M generate less stimulating activity. This biphasic concentration curve for insulin can be resolved by differential alcohol extraction into two fractions which have antagonistic activity. The production of both substances is enhanced by insulin. Chemical and chromatographic evidence suggest that these substances are identical to the previously described “mediators” which regulate both pyruvate dehydrogenase and adenylate cyclase activities.

Effect of High Fat Weanling Diets Containing Either Medium-Chain Triglycerides or Long-Chain Triglycerides on the Development of Obesity in the Zucker Rat

Zucker rats were early weaned onto either medium-chain (MCT) or long-chain triglycerides (LCT) to examine the effect on the development of obesity. Preobese and lean pups were weaned at 16 days to isocaloric, isonitrogenous liquid diets containing either 65% MCT or LCT (by calories) or to a “stocklike” (5.5% fat, 72.6% carbohydrate) control diet or were pair-fed stocklike diet to MCT-fed rats until day 45. MCT-feeding lowered body weight gain and fat pad weight in obese and lean rats compared to stocklike-fed controls. Additionally, fat cell size and lipoprotein lipase (LPL) activity and hepatic acetyl CoA carboxylase activity were reduced in obese MCT-fed rats compared to obese controls fed stocklike diet. Except for altered LPL activity the effects produced by MCT-feeding were attributable to its anorectic effect. However, all obese rats, including the MCT group, developed an obese body composition and were hyperinsulinemic. The developmental sequence leading to obesity may be derived from a fundamental cellular defect that results in metabolic alterations in different tissues at critical periods of development. Thus, effective treatment of this genetic obesity requires a better understanding of fa gene action.high fat diet hyperinsulinemia lipoprotein lipase body composition

Rapid induction of hepatic acetyl-CoA carboxylase activity after estradiol benzoate injection in the quail

The time course of hepatic Acetyl-CoA carboxylase activity as well as hepatic and plasmatic fatty acids concentrations following a single injection of estradiol benzoate (EB, 0.2 mg/kg) was studied in the quail. Acetyl-CoA carboxylase activity increases rapidly and reaches its peak 3 h after the injection of EB. Similarly, hepatic and plasmatic fatty acids concentrations are significantly increased 6 h after the hormonal injection and attain their highest level 18 h later. These results suggest that estrogen affects the hepatic fatty acids biosynthesis by regulating the conversion of acetyl-CoA to malonyl-CoA.

Hepatic lipogenesis and mobilization of peripheral fats in the formation of alcoholic fatty liver.

Biochemical mechanisms underlying the development of alcoholic fatty liver was investigated. Acute ethanol (EtOH) administration for 3 days by an inhalation method, and continuous EtOH treatments by feeding with liquid diet or drinking water containing EtOH induced a significant increase of hepatic triglycerides (TG). A small but significant increase of TG was also observed in the blood serum. Although hepatic acetyl CoA carboxylase activity, measured in the presence and absence of citrate, was not altered by either acute or chronic EtOH administrations, fatty acid synthetase and malic enzyme activities in the liver were increased by continuous EtOH administration, but not in the acutely EtOH-treated animals. The incorporations of [14C]palmitate and [14C]acetate into hepatic RG were also increased significantly in animals treated continuously with EtOH. The lipoprotein lipase activity in adipose tissues was activated by both acute and continuous EtOH treatments, whereas lipase activity in adipose tissues and the epinephrine-stimulated and cyclic AMP-mediated release of free fatty acid (FFA) from this tissue were not altered by these treatments. These results indicate that acute alcoholic fatty liver is caused mostly by the increased mobilization of FFA from peripheral adipose tissues via the activation of lipoprotein lipase, whereas alcoholic fatty liver induced by continuous EtOH administration involves the increased synthesis of FFA due to the activation of fatty acid synthetase and malic enzyme in the liver in addition to the increased mobilization of peripheral FFA.

HEPATIC LIPOGENESIS AND MOBILIZATION OF PERIPHERAL FATS IN THE FORMATION OF ALCOHOLIC FATTY LIVER

AbstractBiochemical mechanisms underlying the development of alcoholic fatty liver were investigated. Acute ethanol (EtOH) administration for 3 days by an inhalation method, and continuous EtOH treatments by feeding with liquid diet or drinking water containing EtOH induced a significant increase of hepatic triglycerides (TG). A small but significant increase of TG was also observed in the blood serum. Although hepatic acetyl CoA carboxylase activity, measured in the presence and absence of citrate, was not altered by either acute or chronic EtOH administrations, fatty acid synthetase and malic enzyme activities in the liver were increased by continuous EtOH administration, but not in the acutely EtOH-treated animals. The incorporations of [14C]palmitate and [14C]acetate into hepatic RG were also increased significantly in animals treated continuously with EtOH. The lipoprotein lipase activity in adipose tissues was activated by both acute and continuous EtOH treatments, whereas lipase activity in adipose tissues and the epinephrine-stimulated and cyclic AMP-mediated release of free fatty acid (FFA) from this tissue were not altered by these treatments. These results indicate that acute alcoholic fatty liver is caused mostly by the increased mobilization of FFA from peripheral adipose tissues via the activation of lipoprotein lipase, whereas alcoholic fatty liver induced by continuous EtOH administration involves the increased synthesis of FFA due to the activation of fatty acid synthetase and malic enzyme in the liver in addition to the increased mobilization of peripheral FFA.