Acetyl-CoA Carboxylase ; metabolism ; Cell Line ; Curcumin ; pharmacology ; Hepatocytes ; drug effects ; metabolism ; Humans

BACKGROUDN: Recent clinical studies have suggested that statins improve insulin resistance and glucose metabolism in the skeletal muscle of diabetic patients. To evaluate a possible component of this action, we measured free fatty acid oxidation in cultured human skeletal muscle cells (HSMC). METHODS: Seven normal controls and 7 type 2 diabetic patients underwent quadriceps muscle biopsy. The HSMCs (n=14) were treated with or without lovastatin (Lova, 20 micrometer) for 2 days, and the free fatty acid (FFA) oxidation was measured. RESULTS: Lova increased the oxidation of the long-chain FA palmitate to 271.2+/-32.7% of the control (p<0.01). Oxidation of the medium chain FA octanoate also increased after treatment of Lova (158.3+/-21.9%, p<0.05). One pathway of regulation of FFA is through AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation. Following Lova treatment, AMPK phosphorylation did not show a significant change while the total protein expression of AMPK was decreased (73.6+/-6.2% of the control, p<0.01). Lova treatment significantly increased ACC phosphorylation (149.5+/-20.6% of the control, p<0.05). CONCLUSION: Lova increased FFA oxidation by increasing the ACC phosphorylation in human skeletal muscle cells. Stimulation of skeletal muscle FFA oxidation may be one mechanism by which statins act to lower intramyocellular triglyceride and improve insulin action on glucose metabolism.
Acetyl-CoA Carboxylase ; AMP-Activated Protein Kinases ; Biopsy ; Glucose ; Humans* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Insulin ; Insulin Resistance ; Lovastatin* ; Metabolism ; Muscle, Skeletal* ; Phosphorylation ; Quadriceps Muscle ; Triglycerides

Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 µg/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 µg/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 µg/ml MCT/LCT propofol for the subsequent experiments. Four and 8 µg/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.
Acetyl-CoA Carboxylase ; AMP-Activated Protein Kinases ; Cell Survival ; Fatty Acids, Nonesterified ; Hepatocytes ; Intensive Care Units ; Lipid Metabolism ; Liver ; Metabolism ; Phosphorylation ; Propofol ; Triglycerides

Rhemannie Radix Preparata (RRP) has been previously employed in traditional oriental medicine as a treatment for diabetic thirst and improving blood flow. The aim of this study was to evaluate its hypoglycemic control by assaying the activities of key enzymes of carbohydrate metabolism in streptozotocin-(STZ)-induced diabetic rats. Further, RRP extracts were prepared in water (RRPW), in 50% ethanol (RRP50), and in 100% ethanol (RRP100), respectively, and compared for their actions in diabetic rats. The oral treatment of RRP (5 mg/kg b.w./d) to diabetic rats for 21 days resulted in a significant decline in blood glucose by 67% compared to diabetic control rats (P < 0.05). The altered activities of glucokinase, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and acetyl CoA carboxylase (ACC) in the livers of diabetic rats were reversed significantly to near-normal levels by the administration of RRP (P < 0.05). Among the three RRP extracts, RRP100 was the most effective in terms of hypoglycemic action. However, the administration of RRP to diabetic rats did not improve insulin production. The modulatory effects of RRP100 on the attenuation of carbohydrate enzyme activities appear to hold promise for widespread use for the treatment of diabetes in the future.
Acetyl-CoA Carboxylase ; Animals ; Blood Glucose ; Carbohydrate Metabolism ; Ethanol ; Glucokinase ; Gluconates ; Glucosephosphate Dehydrogenase ; Hypoglycemic Agents ; Insulin ; Liver ; Medicine, East Asian Traditional ; Phosphogluconate Dehydrogenase ; Rats ; Thirst ; Water

The aim of the present study was to assess the anti-obesity effects of grape seed extract (GSE) supplement in C57BL/6J mice. Thirty mice were divided into three groups; normal diet control group (ND), high fat diet control group (HD) and high fat diet plus grape seed extract supplemented group (HD+GSE). Results were as follows: 1. GSE supplement reduced the weight gain in mice fed high fat diets; epididymal and back fat weights were lower compared to non-supplemented HD group. 2. Blood lipid concentrations were lower in the HD+GSE group than in the HD group. Serum HDL-C concentrations were higher in the HD+GSE group compared with the other groups. 3. The concentrations of acid-insoluble acylcarnitines (AIAC) in serum and liver were higher in the HD+GSE group than in the HD group. 4. GSE supplementation increased mRNA levels of lipolytic genes such as carnitine palmitoyltransferase-1 (CPT-1) and decreased mRNA levels of lipogenic genes such as acetyl CoA carboxylase (ACC). These findings suggest that grape seed extract supplements in high fat diet might normalize body weight, epididymal and back fat weights, lipid concentrations, and carnitine levels through controlling lipid metabolism.
Acetyl-CoA Carboxylase ; Animals ; Body Weight ; Carnitine ; Diet ; Diet, High-Fat ; Gene Expression ; Grape Seed Extract ; Lipid Metabolism ; Liver ; Mice ; Obesity ; RNA, Messenger ; Vitis ; Weight Gain ; Weights and Measures

Mammalian acetyl-CoA carboxylase (ACC) is present in two isoforms, alpha and beta, both of which catalyze formation of malonyl-CoA by fixing CO2 into acetyl-CoA. ACC-alpha is highly expressed in lipogenic tissues whereas ACC-beta is a predominant form in heart and skeletal muscle tissues. Even though the tissue-specific expression pattern of two ACC isoforms suggests that each form may have a distinct function, existence of two isoforms catalyzing the identical reaction in a same cell has been a puzzling question. As a first step to answer this question and to identify the possible role of ACC isoforms in myogenic differentiation, we have investigated in the present study whether the expression and the subcellular distribution of ACC isoforms in H9c2 cardiac myocyte change so that malonyl-CoA produced by each form may modulate fatty acid oxidation. We have observed that the expression levels of both ACC forms were correlated to the extent of myogenic differentiation and that they were present not only in cytoplasm but also in other subcellular compartment. Among the various tested compounds, short-term treatment of H9c2 myotubes with insulin or okadaic acid rapidly increased the cytosolic content of both ACC isoforms up to 2 folds without affecting the total cellular ACC content. Taken together, these observations suggest that both ACC isoforms may play a pivotal role in muscle differentiation and that they may translocate between cytoplasm and other subcellular compartment to achieve its specific goal under the various physiological conditions.
Acetyl-CoA Carboxylase/metabolism* ; Acetyl-CoA Carboxylase/drug effects ; Animal ; Cell Differentiation/drug effects ; Cell Line ; Cell Membrane Permeability ; Chromones/pharmacology ; Cytosol/enzymology* ; Cytosol/drug effects ; Digitonin/pharmacology ; Immunoblotting ; Insulin/pharmacology* ; Isoenzymes ; Morpholines/pharmacology ; Myocardium/cytology ; Okadaic Acid/pharmacology* ; Phosphorylation ; Rats

Acetyl CoA carboxylase contents in liver cytosol of rats refed a high carbohydrate diet or injected with insulin were measured by an immunoassay method in order to evaluate the effects of dietary carbohydrate and insulin treatment on the control in the amount of acetyl CoA carboxylase. Acetyl CoA carboxylase was purified 1,552 folds with a specific activity of 3.88 units/mg protein from livers of rats refed a high carbohydrate diet for 3 days following a 3-day fasting and the antibody was generated against the purified acetyl CoA carboxylase in a rabbit. Treatment of insulin (1.5 units/100g BW) and a high carbohydrate diet increased the amount of acetyl CoA carboxylase in liver cytosol by 3 times and 10 times, respectively, when compared to the enzyme content found in the control. The synthetic ratio of acetyl CoA carboxylase to total cytosolic proteins was 4 times higher in the insulin-treated group and 10 times higher in the high carbohydrated diet-treated group than the control group. The polysomal RNA contents in liver cytosols were 279% of the control in the insulin-treated group and 365% of the control in the high carbohydrate diet group. Also, the nascent chain of acetyl CoA carboxylase in polysome were 158% of the control in the insulin-treated group and 311% of the control in the high carbohydrate treated group. From these results, it is assumed that the increase of acetyl CoA carboxylase content in the rat liver cells by insulin treatment, or high carbohydrate diet refeeding has resulted from the increased polysomal acetyl CoA carboxylase mRNA, which is directly related to the biosynthesis of this enzyme.
Acetyl-CoA Carboxylase/*metabolism ; Animal ; Cytosol/*metabolism ; Dietary Carbohydrates/*administration and dosage ; Insulin/*pharmacology ; Ligases/*metabolism ; Liver/enzymology/*metabolism ; Male ; RNA, Messenger/*metabolism ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't

Acetyl CoA carboxylase contents in liver cytosol of rats refed a high carbohydrate diet or injected with insulin were measured by an immunoassay method in order to evaluate the effects of dietary carbohydrate and insulin treatment on the control in the amount of acetyl CoA carboxylase. Acetyl CoA carboxylase was purified 1,552 folds with a specific activity of 3.88 units/mg protein from livers of rats refed a high carbohydrate diet for 3 days following a 3-day fasting and the antibody was generated against the purified acetyl CoA carboxylase in a rabbit. Treatment of insulin (1.5 units/100g BW) and a high carbohydrate diet increased the amount of acetyl CoA carboxylase in liver cytosol by 3 times and 10 times, respectively, when compared to the enzyme content found in the control. The synthetic ratio of acetyl CoA carboxylase to total cytosolic proteins was 4 times higher in the insulin-treated group and 10 times higher in the high carbohydrated diet-treated group than the control group. The polysomal RNA contents in liver cytosols were 279% of the control in the insulin-treated group and 365% of the control in the high carbohydrate diet group. Also, the nascent chain of acetyl CoA carboxylase in polysome were 158% of the control in the insulin-treated group and 311% of the control in the high carbohydrate treated group. From these results, it is assumed that the increase of acetyl CoA carboxylase content in the rat liver cells by insulin treatment, or high carbohydrate diet refeeding has resulted from the increased polysomal acetyl CoA carboxylase mRNA, which is directly related to the biosynthesis of this enzyme.
Acetyl-CoA Carboxylase/*metabolism ; Animal ; Cytosol/*metabolism ; Dietary Carbohydrates/*administration and dosage ; Insulin/*pharmacology ; Ligases/*metabolism ; Liver/enzymology/*metabolism ; Male ; RNA, Messenger/*metabolism ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't

OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
AMP-Activated Protein Kinases/metabolism* ; Acetyl-CoA Carboxylase/metabolism* ; Adiponectin/metabolism* ; Animals ; Antidepressive Agents/pharmacology* ; China ; Depression/drug therapy* ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Glucose ; Hypothalamus/metabolism* ; Mice ; Receptors, Adiponectin/metabolism*

BACKGROUNDCurrently it is unclear whether lipid accumulation occurs in a particular sequence and its relationship with whole body insulin resistance (IR). This study aimed to answer this question.

METHODSMale Sprague-Dawley (SD) rats were fed on a normal or a high-fat diet for 20 weeks. Serum triglycerides (TG), serum free fatty acids (FFA), fasting plasma glucose (FPG), and liver and skeletal muscle TG were measured. The glucose infusion rate (GIR) and mRNA levels of acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase-1 (CPT-1) in the liver and skeletal muscle were determined at different stages.

RESULTSCompared with rats fed on the normal diet, serum FFA was not significantly increased in rats fed on the high-fat diet until 20 weeks. In contrast, liver TG was significantly increased by the high-fat diet by four weeks (20-fold; P < 0.01), and remained elevated until the end of the study. However, skeletal muscle TG was not significantly increased by the high-fat diet until 20 weeks (10.6-fold; P < 0.01), and neither was the FPG. The GIR was significantly reduced (1.6-fold; P < 0.01) by the high-fat diet after 8 weeks. The mRNA levels of ACC gradually increased over time and CPT-1 decreased over time, in both the liver and skeletal muscle in rats fed the high-fat diet.

CONCLUSIONSLipid accumulation in the liver occurs earlier than lipid accumulation in the skeletal muscle. Fatty liver may be one of the early markers of whole body IR. Changes in the gene expression levels of ACC and CPT-1 may have important roles in the process of IR development.

Acetyl-CoA Carboxylase ; genetics ; Animals ; Blood Glucose ; analysis ; Carnitine O-Palmitoyltransferase ; genetics ; Fatty Acids, Nonesterified ; blood ; Fatty Liver ; etiology ; Insulin Resistance ; Lipid Metabolism ; Liver ; metabolism ; Male ; Muscle, Skeletal ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; metabolism