The effects of estradiol administration of the hepatic activities of some enzymes of carbohydrate, amino acid and lipid metabolism in the immature pullet.

Two experiments were performed to examine the effects of intramuscular estradiol administration on the hepatic specific activities of some enzymes of lipid, carbohydrate and amino acid metabolism in the immature fowl. Estradiol increased the specific activities of the hepatic lipogenic enzymes, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP), but had no effects on the activities of the glycolytic, gluconeogenic and amino acid metabolising enzymes except for pyruvate kinase and glutamate dehydrogenase which were reduced in activity in both experiments. The results indicate that the estrogen-induced increase in hepatic lipid biosynthesis is due to a specific effect on lipid metabolism and not to a general increase in liver metabolism.     

Covariance of tricarboxylate carrier activity and lipogenesis in liver of polyunsaturated fatty acid (n-6) fed rats.

The mitochondrial tricarboxylate (citrate) carrier plays an important role in hepatic intermediary metabolism because, among other functions, it supplies the cytosol with acetyl units for fatty-acid synthesis. In this study, the effect of polyunsaturated fatty acids (PUFA, n-6) on the function of this mitochondrial transporter and on lipogenic enzyme activities was investigated by feeding rats for 4 weeks with a 15%-fat diet composed of high linoleic safflower oil. Citrate transport was strongly reduced in liver mitochondria isolated from PUFA-treated rats. A reduced transport activity was also observed when solubilized mitochondrial citrate carrier from PUFA-treated rats was reconstituted into liposomes. In the same animals, a decrease of cytosolic lipogenic enzyme activities was observed. These results indicate a coordinated modulation of citrate carrier and of lipogenic enzyme activities by PUFA feeding. Kinetic analysis of the carrier activity showed that only V(max) decreased, whereas K(m) was almost virtually unaffected. The PUFA-mediated effect is most likely due to the reduced mRNA level and lower content of the citrate carrier protein observed in the safflower oil-fed rats.     

Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic,gluconeogenic and lipogenic enzymes

Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADPlinked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4fold higher blood glucose level and a 0.7fold lower body weight compared to normal controls. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities of gluconeogenic enzymes were higher in both liver and kidney during diabetes, however the activities of the lipogenic enzymes were decreased in both tissues during diabetes. Trigonella seed powder treatment to diabetic rats for 21 days brought down the elevated fasting blood glucose levels to control levels. The altered enzyme activities were significantly restored to control values in both the liver and kidney after Trigonella seed powder treatment. The therapeutic role of Trigonella seed powder in type1 diabetes as exemplified in this study can be attributed to the change of glucose and lipid metabolising enzyme activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney. These biochemical effects exerted by Trigonella seeds make it a possible new therapeutic in type1 diabetes.     

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

Ghrelin is a gastric hormone increased during caloric restriction and fat depletion. A role of ghrelin in the regulation of lipid and energy metabolism is suggested by fat gain independent of changes in food intake during exogenous ghrelin administration in rodents. We investigated the potential effects of peripheral ghrelin administration (two times daily 200-micrograms [DOSAGE ERROR CORRECTED] sc injection for 4 days) on triglyceride content and mitochondrial and lipid metabolism gene expression in rat liver and muscles. Compared with vehicle, ghrelin increased body weight but not food intake and circulating insulin. In liver, ghrelin induced a lipogenic and glucogenic pattern of gene expression and increased triglyceride content while reducing activated (phosphorylated) stimulator of fatty acid oxidation, AMP-activated protein kinase (AMPK, all P < 0.05), with unchanged mitochondrial oxidative enzyme activities. In contrast, triglyceride content was reduced (P < 0.05) after ghrelin administration in mixed (gastrocnemius) and unchanged in oxidative (soleus) muscle. In mixed muscle, ghrelin increased (P < 0.05) mitochondrial oxidative enzyme activities independent of changes in expression of fat metabolism genes and phosphorylated AMPK. Expression of peroxisome proliferator-activated receptor-gamma, the activation of which reduces muscle fat content, was selectively increased in mixed muscle where it paralleled changes in oxidative capacities (P < 0.05). Thus ghrelin induces tissue-specific changes in mitochondrial and lipid metabolism gene expression and favors triglyceride deposition in liver over skeletal muscle. These novel effects of ghrelin in the regulation of lean tissue fat distribution and metabolism could contribute to metabolic adaptation to caloric restriction and loss of body fat.     

Olive oil increases the hepatic triacylglycerol content in mice by a distinct influence on the synthesis and oxidation of fatty acids

Diet supplementation with olive oil exerts beneficial effects on an organism, even if an increase in the level of hepatic lipids has been concomitantly observed. This study was therefore designed to investigate whether the stimulation of lipogenesis was responsible for the olive oil-induced hepatic fat accumulation. In mice fed for 8 weeks with an olive oil-enriched diet, an increase of about 2.6 fold in the level of liver triglycerides was found in comparison to animals fed with a corn oil-containing diet. Despite that, no increase in the activities of cytosolic lipogenic enzymes or of the mitochondrial tricarboxylate carrier was found; on the contrary, a decrease in the activity of carnitine palmitoyltransferase I was observed. This impairment of fatty acid oxidation, which was not apparent in corn oil-fed animals, may have had a role in the increase of hepatic lipid content found in the olive oil-fed mice.     

Conjugated linoleic acid and hepatic lipogenesis in mouse: role of the mitochondrial citrate carrier

Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid metabolism. In particular, CLA administration to mice reduces body fat mass with a concomitant lipid accumulation in the liver. We investigated the effects of CLA on the activity of the mitochondrial citrate carrier (CIC), which is implicated in hepatic lipogenesis. The transport activity of the CIC, measured both in intact mitochondria and in the proteoliposomes, progressively increased with the duration of CLA feeding. An increase in the CIC activity of approximately 1.7-fold was found in 16 week CLA-treated mice with respect to control animals. A kinetic analysis showed a 1.6-fold increase in the V(max) of citrate transport but no change in the K(m) value. Western blot experiments revealed an increase of approximately 1.7-fold in the expression of CIC after CLA treatment. A strict correlation between the increase in CIC activity and the stimulation of the cytosolic lipogenic enzymes was also found. These data indicate that the CIC may play a role in the onset of hepatic steatosis in CLA-fed mice by supplying the carbon source for de novo fatty acid synthesis.     

Citrate carrier activity and cardiolipin level in eel (Anguilla anguilla) liver mitochondria

The activity of the tricarboxylate (citrate) carrier has been assayed in intact liver mitochondria from yellow eel (Anguilla anguilla) and compared to that from rat. The eel-citrate carrier specific activity was approximately 1.7-fold higher than that assayed in rat-liver mitochondria. The content of the main mitochondrial phospholipids, phosphatidylethanolamine and phosphatidylcholine, did not show a significant difference between the two species, while in eel a higher cardiolipin level was observed. Fatty acid composition of eel-liver mitochondrial phospholipids was characterised by a large amount of unsaturated fatty acids, dominated by octadecaenoic acid (C(18:1) (n-9)) and docosahexaenoic acid (C(22:6) (n-3)). The cardiolipin fatty acid pattern of eel-liver mitochondria showed, with respect to the rat, a higher C(20:5) (n-3) and C(22:6) (n-3) content and a lower amount of C(18:2) (n-6) and C(20:4) (n-6). A noticeable activity of lipogenic enzymes was also detected in eel liver cytosol. The results of this study suggest that the remarkable activity of the citrate carrier in eel-liver mitochondria can most likely be ascribed to a considerable cardiolipin level. A covariance of citrate carrier and lipogenic enzyme activities was observed.     

Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis

The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property.     

Role of pyruvate carboxylase in fatty acid synthesis: Alterations during preadipocyte differentiation

Transport of mitochondrial acetyl units to the cytoplasm for fatty acid synthesis via the citrate cleavage pathway requires replenishment of mitochondrial oxaloacetate. Pyruvate carboxylase is though to fulfill this role although compelling evidence has been lacking. During lipogenic differentiation of 3T3-L1 preadipocytes, pyruvate carboxylase activity rises 18-fold in close coordination with fat accumulation and the activity of ATP-citrate lyase, an established lipogenic enzyme. The activities of enzymes less directly related to lipogenesis rise only 3–5-fold while other unrelated enzymes do not increase significantly. These results indicate that pyruvate carboxylase is in fact a lipogenic enzyme.     

The "direct mitogen" lead nitrate causes an intensification in lipid peroxidation and Ito cell activation in the rat liver]

We have used biochemical and immunohistochemical methods to study lipid peroxidation and activation of Ito cells in rat liver after a single administration of lead nitrate, a "direct mitogen". Lead nitrate was shown to injure hepatocytes through an increased lipid peroxidation. Response to the injury included increase in the proliferative activity of parenchymal and sinusoidal liver cells. In addition, activation of Ito cells has been noted, which manifested as increased expression of desmin and increased proliferation. However, no transformation of Ito cells into myofibroblasts has been observed. We discuss the possible role of Ito cell activation in creating conditions for the proliferation of liver parenchymal cells after the injury by lead nitrate.     

Mitochondrial Ageing and the Beneficial Role of α-Lipoic Acid

Oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the ageing process. Mitochondria are known to be a rich source for the production of free radicals and, consequently, mitochondrial components are susceptible to lipid peroxidation (LPO) that decreases respiratory activity. In the present investigation, we have evaluated mitochondrial LPO, 8-oxo-dG, oxidized glutathione, reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and electron transport chain (ETC) complex activities in the brain of young versus aged rats. In aged rats, the contents of LPO, oxidized glutathione and 8-oxo-dG were high whereas reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities were found to be low. Lipoic acid administration to aged rats reduced the levels of mitochondrial LPO, 8-oxo-dG and oxidized glutathione and enhanced reduced glutathione, ATP, lipoic acid and ETC complex activities. In young rats lipoic acid administration showed only minimal lowering the levels of LPO, 8-oxo-dG and oxidized glutathione and slight increase in the levels of reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities. These findings suggest that the dithiol, lipoic acid, provides protection against age-related oxidative damage in the mitochondria of aged rats.     

Effects of sodium-orthovanadate and<Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes

Sodium-orthovanadate (SOV) and seed powder ofTrigonella foenum graecum Linn. (common name: fenugreek, family: Fabaceae) (TSP) besides being potential hypoglycemic agents have also been shown to ameliorate altered lipid metabolism during diabetes. This study evaluates the short-term effect of oral administration of SOV and TSP separately and in concert (for 21 days) on total lipid profile and lipogenic enzymes in tissues of alloxan diabetic rats. Diabetic rats showed 4-fold increase in blood glucose. The level of total lipids, triglycerides and total cholesterol in blood serum increased significantly during diabetes. During diabetes the level of total lipids increased significantly (P < 0001) in liver and in kidney by 48% and 55%, respectively, compared to control. Triglycerides level increased by 32% (P < 001) in liver and by 51% (P < 0005) in kidney, respectively, compared to control. Total cholesterol level also increased significantly in both liver and kidney (P < 0.01 andP < 0001, respectively). The activities of NADP-linked enzymes; namely glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and the activities of lipogenic enzymes namely ATP-citrate lyase ΜTP-CL) and fatty acid synthase (FAS) were decreased significantly in liver and increased in kidney during diabetes as compared to control. SOV and TSP administration to diabetic animals prevented the development of hyperglycemia and alteration in lipid profile in plasma and tissues and maintained it near normal. Maximum prevention was observed in the combined treatment with lower dose of SOV (0.2%) after 21 days. We are presenting for the first time effectiveness of combined treatment of SOV and TSP in amelioration of altered lipid metabolism during experimental type-I diabetes     

Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats.

Mitochondrial dysfunction appears to contribute to some of the loss of function accompanying ageing. Mitochondria from aged tissue use oxygen inefficiently impairing ATP synthesis and results in increased oxidant production. A high flux of oxidants not only damages mitochondria, but other important cell biomolecules as well. In the present investigation, the levels of lipid peroxidation, oxidized glutathione, non-enzymatic antioxidants and the activities of mitochondrial enzymes were measured in liver and kidney mitochondria of young and aged rats before and after lipoic acid supplementation. In both liver and kidney increase in the levels of mitochondrial lipid peroxidation and oxidized glutathione and decrease in the levels of antioxidants and the activities of mitochondrial enzymes were observed in aged rats. DL-alpha-lipoic acid supplemented aged rats showed a decrease in the levels of lipid peroxidation and oxidized glutathione and increase in the levels of reduced glutathione, vitamins C and E and the activities of mitochondrial enzymes like isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, NADH-dehydrogenase and cytochrome-c-oxidase. Thus, lipoic acid reverses the age-associated decline in endogenous low molecular weight antioxidants and mitochondrial enzymes and, therefore, may lower the increased risk of oxidative damage that occurs during ageing. From our results it can be concluded that lipoic acid supplementation enhances the activities of mitochondrial enzymes and antioxidant status and thereby protects mitochondria from ageing.     

Age-dependent variations in mitochondrial and cytosolic antioxidant enzymes and lipid peroxidation in different regions of central nervous system of guinea pigs

The age-related changes in the activities of antioxidant enzymes of mitochondrial and cytosolic fractions were measured in different regions of the central nervous system (CNS) in 10 and 32 months old guinea pigs. In old animals, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were reduced (p < 0.05) in all the regions of CNS studied but catalase (CAT) declined significantly only in the cerebral cortex, hypothalamus and cerebellum. Glutathione reductase (GRd) activity declined in cerebral cortex and hypothalamus in the cytosolic fractions and only in cerebellum in the mitochondrial fraction. It is concluded that age-related decline in the activities of antioxidant enzymes is both region and enzyme specific. The endogenous lipid peroxide was found to be significantly higher (p < 0.05) in the 32 month old animals whereas, lipid peroxidation after incubating the tissue homogenate in air was found to be lower (p < 0.05). The in vitro mitochondrial lipid peroxidation decreased with age. The results indicate that accumulation of lipid peroxides takes place with ageing but the susceptibility of lipid peroxidation decreases in the older animals.     

Development of hepatic and adipose tissue lipogenic enzymes and insulinemia during suckling and weaning on to a high-fat diet in Zucker rats

This study was designed to monitor the developmental changes in insulinemia and lipogenic enzyme activities in both inguinal adipose tissue and liver during suckling (7, 9, 14, and 17 days of age) and weaning (22 and 30 days of age) on to either a low-fat or a high-fat diet in lean (Fa/fa) and obese (fa/fa) rats. Tissues were removed through surgery and genotypes were retrospectively determined. During suckling, there was no difference in liver enzyme activities between the two groups. In contrast, adipose tissue fatty acid synthetase was increased by 50% and citrate cleavage enzyme and malic enzyme by 30% by 9 days of age. By 17 days of age, there was a threefold elevation in these enzyme activities and 6-phosphogluconic dehydrogenase and a twofold increase in glucose-6-phosphate dehydrogenase per inguinal fat pad in fa/fa versus Fa/fa. Consistent with these results, fat pad weight was increased by 20%, 50%, and 100% at 9, 14, and 17 days of age, respectively, in obese as compared to lean pups. However only by 17 days of age could a slight but significant increase in insulin level be detected in obese pups. Enlargement of inguinal fat pad accelerated after weaning on to a low-fat diet and still more after weaning on to a high-fat diet. Weaning on to a low-fat diet elicited an induction of hepatic lipogenic enzymes two or three times greater in fa/fa than in lean pups, while weaning on to a high-fat diet blunted the differences between genotypes. The lipogenic enzyme activities displayed per total inguinal fat were three to ten times greater in obese than in lean pups, regardless of the diet. However, adipose tissue lipogenic enzyme activities were much lower after weaning on to a high-fat than on to a low-fat diet in obese pups. The high-fat diet was as effective as the low-fat diet in triggering hyperinsulinemia in obese pups. The increased adipose tissue capacity for lipogenesis, starting during the suckling period, could play an important etiologic role in the development and maintenance of obesity in the Zucker rat.-Bazin, R., and M. Lavau. Development of hepatic and adipose tissue lipogenic enzymes and insulinemia during suckling and weaning on to a high-fat diet in Zucker rats.     

The effect of beta-adrenergic agonists on the membrane potential of fat-cell mitochondria in situ.

1. The rate of mammary-gland lipogenesis measured in vivo from 3H2O was suppressed after decreasing the milk demand by decreasing the number of pups from ten to two or three, as well as by giving diets containing lipid [Grigor & Warren (1980) Biochem. J. 188, 61-65]. 2. The specific activities of the lipogenic enzymes fatty acid synthase, glucose 6-phosphate dehydrogenase and 'malic' enzyme increased between 6- and 10-fold in the mammary gland and between 2- and 3-fold in the livers during the first 10 days of lactation. The increases in specific activity coupled with the doubling of liver mass which occurred during pregnancy and lactation resulted in considerable differences in total liver activities when compared with virgin animals. 3. Although consumption of a diet containing 20% peanut oil suppressed the activities of the three lipogenic enzymes in the livers, only the 'malic' enzyme was affected in the mammary glands. 4. In contrast, decreased milk demand did not affect the specific activities of any of the liver enzymes, whereas it resulted in suppression of all three lipogenic enzymes of the mammary glands. There was no effect on either the cytoplasmic malate dehydrogenase or the lactate dehydrogenase of the mammary gland. 5. In all the experiments performed, the activity of the fatty acid synthase correlated with the amount of material precipitated by the rabbit antibody raised against rat fatty acid synthase.     

Interactions of betulinic acid with xenobiotic metabolizing and antioxidative enzymes in DMBA-treated Sprague Dawley female rats

Cancer chemoprevention is related to classical epidemiology and involves the use of agents that inhibit, delay, or reverse the carcinogenesis that occurs as a result of accumulation of mutations and increased proliferation. Betulinic acid is known for its cytotoxic effects against a panel of cancer cell lines. In the present study, interactions of betulinic acid (BA) with xenobiotic metabolizing enzymes including mixed function oxidases (cytochrome b5, P420, P450, NADPH cytochrome P450 reductase, and NADH cytochrome b5 reductase), phase II enzymes (GST, DT-diaphorase, γ-glutamyl transpeptidase), LDH, antioxidative enzymes (glutathione reductase, SOD, catalase, ascorbate peroxidase, and guaiacol peroxidase), and lipid peroxidation are studied alone as well as in the presence of 7,12 dimethylbenzanthracene (DMBA)—a potent carcinogen using Sprague Dawley female rats. The effect of BA on reduced glutathione content and protein content is also taken into consideration. It has been found that administration of BA decreased the level of mixed function oxidases that are involved in the conversion of carcinogen to electrophile, elevated the level of phase II enzymes which participated in the removal of electrophiles by sulfation, conjugation etc. It has been found that BA effectively removed or neutralized the reactive species by the action of phase II enzymes and such an effect was reflected from the specific activities of antioxidative enzymes which were found to be lower as compared to positive control (DMBA-treated group) and in some cases even that of untreated control. BA was also found to have a pronounced effect in protecting the animals from lipid peroxidation as evident from the reduced levels of TBARS, conjugated diene, and lipid hydroperoxide formation. This study highlights the role of BA in modulating the activities of xenobiotic and antioxidative enzymes that have putative roles in cancer initiation and proliferation.     

Identification of dicarboxylate carrier Slc25a10 as malate transporter in de novo fatty acid synthesis

Mitochondrial solute carrier family 25 member 10 (Slc25a10) transports dicarboxylates such as malate or succinate across the mitochondrial inner membrane. Although fatty acid synthesis in adipose tissue or the liver is initiated by citrate transport in exchange for malate across the mitochondrial membrane, the transporter responsible for supplying malate during citrate transport has not been identified. In the present study, we clarified the role of Slc25a10 in supplying malate for citrate transport and examined the effect of Slc25a10 suppression on the lipogenic pathway and lipid accumulation. We have reported an Slc25a10 increase in white adipose tissue in obese mouse models and a decrease in a fasted mouse model using expression profiles. Next, we examined the effect of Slc25a10 suppression by small interfering RNA on citrate transport in the lipogenic cell lines HepG2 and 3T3-L1. We observed that inhibition of malate transport by Slc25a10 suppression significantly reduced the citrate transport from the mitochondria to the cytosol. We also found that suppression of Slc25a10 down-regulated the lipogenic pathway, indicated by decreases in ACC1 expression and malonyl-CoA level. Furthermore, suppression of Slc25a10 decreased triglyceride lipid accumulation in adipose-differentiated 3T3-L1 cells. These results suggested that Slc25a10 plays an important role in supplying malate for citrate transport required for fatty acid synthesis and indicated that inhibition of Slc25a10 might effectively reduce lipid accumulation in adipose tissues.     

Dietary Enrichment with Fish Oil Prevents High Fat-Induced Metabolic Dysfunction in Skeletal Muscle in Mice

High saturated fat (HF-S) diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO) diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus) and white (extensor digitorum longus) muscles of male and female C57BL/6 mice (n = 9-12/group). Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic and gene expression profile; likewise fish oil was similarly protective in both sexes.     

Combined treatment of sodium orthovanadate and Momordica charantia fruit extract prevents alterations in lipid profile and lipogenic enzymes in alloxan diabetic rats

Momordica charantia Linn., commonly called bitter gourd, is a medicinal plant used in the Ayurvedic system of medicine for treating various diseases including diabetes mellitus. Sodium orthovanadate (SOV) is also well-known insulin mimetic and an antidiabetic compound. Our laboratory has been using reduced doses of SOV along with administration of herbal extracts to alloxan diabetic rats and has established this combination as a good antihyperglycemic agent. The present study was undertaken to investigate the effects of treatment of Momordica fruit extract (MFE) and sodium orthovanadate, separately and in combination, on serum and tissue lipid profile and on the activities of lipogenic enzymes in alloxan induced diabetic rats. The results show that there was a significant (p < 0.01) increase in serum total lipids, triglycerides and total cholesterol levels after 21 days of alloxan diabetes. In the liver and kidney of diabetic rats the levels of total lipids and triglycerides also increased significantly (p < 0.01) while levels of total cholesterol decreased significantly (p < 0.01 and p < 0.05, respectively). The lipogenic enzymes showed decreased activity in the diabetic liver, while in kidney they showed an increased activity. When compared with the controls these changes were significant. The treatment of alloxan diabetic rats with MFE and SOV prevented these alterations and maintained all parameters near control values. Most effective prevention was however observed in a combined treatment of Momordica with a reduced dose of SOV (0.2%). The results suggest that Momordica fruit extract and SOV exhibit hypolipidemic as well as hypoglycemic effect in diabetic rats and their effect is pronounced when administered in combination. (Mol Cell Biochem 268: 111–120, 2005)