The metabolic effects of prolonged starvation and refeeding in sturgeon and rainbow trout

The present study examines the particular metabolic strategies of the sturgeon Acipenser naccarii in facing a period of prolonged starvation (72 days) and subsequent refeeding (60 days) compared to the trout Oncorhynchus mykiss response under similar conditions. Plasma metabolites, endogenous reserves, and the activity of intermediate enzymes in liver and white muscle were evaluated. This study shows the mobilization of tissue reserves during a starvation period in both species with an associated enzymatic response. The sturgeon displayed an early increase in hepatic glycolysis during starvation. The trout preferentially used lactate for gluconeogenesis in liver and white muscle. The sturgeon had higher lipid-degradation capacity and greater synthesis of hepatic ketone bodies than the trout, although this latter species also showed strong synthesis of ketone bodies during starvation. During refeeding, the metabolic activity present before starvation was recovered in both fish, with a reestablishment of tissue reserves, plasmatic parameters (glucemia and cholesterol), and enzymatic activities in the liver and muscle. A compensatory effect in enzymes regarding lipids, ketone bodies, and oxidative metabolism was displayed in the liver of both species. There are metabolic differences between sturgeon and trout that support the contention that the sturgeon has common characteristics with elasmobranchs and teleosts.     

Insulin and glucagon family peptides in relation to activities of hepatic hexokinase and other enzymes in fed and starved Atlantic salmon (Salmo salar) and cod (Gadus morhua).

1. Plasma levels of insulin, glucagon, and glucagon-like peptide (Glp) were all reduced by starvation of salmon and cod. In the salmon the drop in Glp was larger than in insulin and glucagon. 2. After starvation the activity of hexokinase (EC 2.7.1.1) was increased in salmon liver, but decreased in cod liver. The salmon hepatic hexokinase activity was inversely correlated with the Glp/insulin ratio. 3. Activities of hepatic glycogen phosphorylase (EC 2.4.1.1) and phosphofructokinase (EC 2.7.1.11) were increased in starved as compared to fed salmon. In cod, starvation resulted in decreased or unchanged activity of phosphorylase. This discrepancy may be related to different degrees of environmental and handling stress. 4. Intraperitoneal injection of human insulin in salmon gave increased hepatic phosphorylase and hexokinase activities and reduced plasma levels of glucagon, Glp and endogenous fish insulin at sampling after 30 hr. 5. No differences in hepatic hexokinase activities or plasma hormone levels were observed between cod fed low and high carbohydrate diets. Apparently, regulation of glucose phosphorylation by dietary carbohydrate does not occur.     

Hepatoprotective potential of new steroid against carbon tetrachloride-induced hepatic injury

The present study was designed to evaluate the hepatoprotective effects of newly isolated stigmast-4, 20 (21), 23-trien-3-one (STO) against carbon tetrachloride-induced hepatic injury in Wistar albino rats. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl₄ (0.5 mL/kg CCl₄ in olive oil) in experimental rats. Three different doses (2.5, 5.0, and 10 mg/kg, p.o) of STO was administered to the test groups during whole experimental protocol. Changes in the activity of serum ALT, AST, ALP, TB, and TP, anti-oxidant enzymes like SOD, CAT, GPx, GST, and LPO were studied in CCl₄-induced hepatocellular carcinogenesis. The altered levels of serum ALT, AST, ALP, TB, and TP restored toward normalization significantly by STO in a dose dependant manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, it also produced a significant and dose-dependent reversal of CCl₄-diminished activity of anti-oxidant enzymes like SOD, CAT, GPx, GST, and the reduced CCl₄-elevated level of LPO. STO significantly prevented the increased levels of serum markers, also suppressed the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and markedly increases the endogenous anti-oxidant enzymes level in CCl₄-induced hepatic injury.     

Growth, starvation and enzyme activity in white muscle of atlantic cod: at what point do muscle metabolic capacities change?

Muscle protein decreases only during prolonged starvation of Atlantic cod (Gadus morhua, Gadidae), but in the absence of protein renewal, muscle metabolic capacities may decrease before marked loss of muscle protein. This study aimed at elucidating the threshold at which decreases in growth and condition reduce muscle metabolic capacities, as well as identifying the indicators that best explain changes in metabolic capacities. To generate a wide spectrum of individual growth rates, condition factors and proximate compositions, cod showing different initial condition were fed or starved for different periods of time. The relationships between muscle proteins and metabolic enzyme activities (LDH and CCO) on one hand, and growth rate, condition factor, hepato- and gonadosomatic index and muscle and liver water and energy contents, on the other hand, were examined through linear regression models. Multiple linear regressions explained a large proportion of the observed variability in proteins and enzyme activities. Changes in LDH and CCO activities were not driven by changes in growth rate. Muscle water was the only significant correlate for both enzymes. Enzyme activities decreased as soon as muscle water began to rise. Increases in water content from 79 to 92% resulted in a 10-fold decrease in LDH and CCO activities.     

Lysosomal enzyme activities in muscle following starvation and refeeding in the saithe Pollachius virens L

Saithe (Pollachius virens L.) were starved for 66 days at 10 degrees C and activities of aryl sulfatase, acid proteinase, beta-glucuronidase, RNAase and acid phosphatase measured in homogenates prepared from fast and slow myotomal muscles. In fed fish, hydrolase activities were generally higher in slow than fast muscles. With the exception of acid proteinase activity in slow muscle, the activities of all the lysosomal enzymes increased by 70 to 100% during starvation. In general, there was a proportionally larger increase in the hydrolase activities in fast than in slow muscle. In a second experiment, fish were starved for 74 days, and refed for up to 52 days. The increases in aryl sulfatase and acid proteinase activity produced in fast muscle with starvation were found to be rapidly reversed by refeeding. Lysosomal enzyme activities in fish sampled after 10 days refeeding were not significantly different from fed controls. Membrane fractions enriched in aryl sulfatase activity were prepared from the fast muscle of 66-day starved fish. These were capable of degrading both myosin heavy chains and actin to lower molecular weight peptides at acid (pH 5.0), but not at neutral pH. The results suggest a role for lysosomal enzymes in the breakdown of myofibrillar proteins during starvation.     

Metabolic responses to prolonged starvation, food restriction, and refeeding in the brown trout, Salmo trutta: oxidative stress and antioxidant defenses

The effects of long-term starvation and food restriction (49 days), followed by refeeding (21 days) have been studied with respect to antioxidant defense in the liver and gills (branchial tissues) of the brown trout, Salmo trutta. Malondialdehyde levels in both tissues increased in parallel with starvation and food restriction and these values did not return to normal after the refeeding period. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in liver and gills increased during the 49 days of starvation, but glucose-6-phosphate dehydrogenase (G6PD) activities decreased. Glutathione S-transferase (GST) activity decreased in the liver at the 49th day of starvation, but increased in the branchial tissues. Some of the antioxidant enzyme activities (such as hepatic GST and branchial G6PD) returned to control values of fed fish after the refeeding period, but others (e.g. hepatic SOD and branchial GPx) did not return to normal values. In conclusion, our study indicates that total or partial food deprivation induces oxidative stress in brown trout.     

Growth,starvation and enzyme activity in white muscle of atlantic cod: at what point do muscle metabolic capacities change?

Muscle protein decreases only during prolonged starvation of Atlantic cod (Gadus morhua, Gadidae), but in the absence of protein renewal, muscle metabolic capacities may decrease before marked loss of muscle protein. This study aimed at elucidating the threshold at which decreases in growth and condition reduce muscle metabolic capacities, as well as identifying the indicators that best explain changes in metabolic capacities. To generate a wide spectrum of individual growth rates, condition factors and proximate compositions, cod showing different initial condition were fed or starved for different periods of time. The relationships between muscle proteins and metabolic enzyme activities (LDH and CCO) on one hand, and growth rate, condition factor, hepato- and gonadosomatic index and muscle and liver water and energy contents, on the other hand, were examined through linear regression models. Multiple linear regressions explained a large proportion of the observed variability in proteins and enzyme activities. Changes in LDH and CCO activities were not driven by changes in growth rate. Muscle water was the only significant correlate for both enzymes. Enzyme activities decreased as soon as muscle water began to rise. Increases in water content from 79 to 92% resulted in a 10-fold decrease in LDH and CCO activities.     

The influence of changes in food availability on the activities of key degradative and metabolic enzymes in the liver and epaxial muscle of the golden perch

This study investigated the influence of feeding frequency on the activities of important degradative enzymes and potentially rate-limiting enzymes in glycolysis and gluconeogenesis in the liver and white epaxial muscle of Macquaria ambigua . Adult animals were either fed daily to satiety (fed), deprived of food for up to 180 days (starved), or starved for 150 days then fed daily to satiety for 30 days (starved/fed). The activities of lipolytic, glycogenolytic and glycolytic enzymes in the livers of starved fish were maintained as long as liver energy stores were available, but became significantly reduced following their exhaustion indicating a decline in metabolism in response to prolonged starvation. The response of epaxial muscle metabolism to changes in food availability was different to that of the liver, as no significant change in the activities of muscle lipolytic or glycogenolytic enzymes were observed in response to starvation. Muscle tissue metabolism was reduced after 60–90 days of starvation, but then returned to prestarvation levels.     

The effects of selenium on oxidative stress biomarkers in the freshwater characid fish matrinxã, Brycon cephalus (Günther, 1869) exposed to organophosphate insecticide Folisuper 600 BR (methyl parathion)

Methyl parathion (MP), an organophosphate widely applied in agriculture and aquaculture, induces oxidative stress due to free radical generation and changes in the antioxidant defense system. The antioxidant roles of selenium (Se) were evaluated in Brycon cephalus exposed to 2 mg L(-1) of Folisuper 600 BR (MP commercial formulation - MPc, 600 g L(-1)) for 96 h. Catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) levels in the gills, white muscle and liver were evaluated in fish fed on diets containing 0 or 1.5 mg Se kg(-1) for 8 weeks. In fish treated with a Se-free diet, the MPc exposure increased SOD and CAT activities in all tissues. However, the GPx activity decreased in white muscle and gills whereas no alterations were observed in the liver. MPc also increased GST activity in all tissues with a concurrent decrease in GSH levels. LPO values increased in white muscle and gills and did not change in liver after MPc exposure. A Se-supplemented diet reversed these findings, preventing increases in LPO levels and concurrent decreases in GPx activity in gills and white muscle. Similarly, GSH levels were maintained in all tissue after MPc exposure. These results suggest that dietary Se supplementation protects cells against MPc-induced oxidative stress.     

Oxidative stress biomarkers in the freshwater characid fish, Brycon cephalus, exposed to organophosphorus insecticide Folisuper 600 (methyl parathion)

Methyl parathion (MP) is an organophosphorus insecticide used worldwide in agriculture and aquaculture due to its high activity against a broad spectrum of insect pests. The effect of a single exposure to 2 mg L(- 1) of a commercial formulation of MP (MPc: Folisuper 600(R), MP 600 g L(- 1)) on catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) of the liver, white muscle and gills of Brycon cephalus was evaluated after 96 h of treatment. MPc exposure resulted in a significant induction of SOD, CAT and GST activity in all tissues. However, the GPx activity decreased significantly in white muscle and gills, whereas no alterations were observed in hepatic GPx activity. MPc also induced a significant increase in LPO values in the white muscle and gills, while hepatic LPO levels did not show any significant alteration. The current data suggest that MPc has oxidative-stress-inducing potential in fish, and that gills and white muscle are the most sensitive organs of B. cephalus, with poor antioxidant potentials. The various parameters studied in this investigation can also be used as biomarkers of exposure to MPc.     

Effect of starvation on tissue and serum gluconeogenic enzymes, alkaline phosphatase and tissue glycogen in the freshwater catfish, Heteropneustes fossilis (Bloch).

The influence of starvation has been studied on tissue and serum G-6Pase F-D-Pase and alkaline phosphatase activities and on the muscle and liver glycogen content of the freshwater catfish H. fossilis (Bloch). A marked increase in G-6Pase and F-D-Pase activities and a fall in the muscle and liver glycogen content recorded during 40 day starvation. The rise in gluconeogenic enzymes during starvation may be due to glucocorticoid stimulation. Alkaline phosphatase activity was found to decline markedly during starvation. The decline in enzyme activity is attributed to some factors like a fall in the rate of synthesis caused by lowered metabolic demands and to electrolyte imbalance caused by tissue overhydration. The fall in glycogen content may be related to the starved condition of the fish. Elevation in glycogen content and alkaline phosphatase activity and a fall in gluconeogenic enzymes were noted when feeding had been resumed.     

The accumulation and synthesis of betaine in winter skate (Leucoraja ocellata)

The present study investigated aspects of betaine metabolism in an elasmobranch fish, the winter skate (Leucoraja ocellata). Based on the level of choline dehydrogenase (ChoDH) activity, the liver and kidney appear to be the major sites of betaine synthesis and the mitochondrial localization of ChoDH and betaine aldehyde dehydrogenase (BADH) indicates that the metabolic organization of betaine synthesis in winter skate is similar to other vertebrates. Food deprivation did not affect white muscle betaine content, and prolonged starvation (70 days) appeared to decrease the total hepatic betaine synthetic capacity. There was no decrease in ChoDH or BADH activity at the mitochondrial level with starvation, suggesting any decrease is due to catabolism of hepatic reserves rather than downregulation of betaine synthesis. Skates fed a high betaine diet (frozen squid approximately 55 micromol g(-1)) had elevated white muscle betaine content compared to those fed a low betaine diet (frozen herring <2 micromol g(-1)); however, high dietary betaine intake did not affect the activity of betaine synthesizing enzymes in liver. Acclimation to elevated salinity (120 and 130% seawater) did not result in an increase in white muscle betaine content. Taken as a whole, the present data suggest that diet is a major determinant of muscle betaine in the winter skate and that betaine is of marginal importance as an intracellular osmolyte in this species.     

Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer     

Quercetin attenuates lindane induced oxidative stress in wistar rats

A wide number of pesticides, including highly persistent organochlorine compounds, such as lindane (γ-Hexachlorocyclohexane), have deteriorative effect on fauna and flora by inducing oxidative stress. Lindane induces cell damage by producing free radicals and reactive oxygen species. Quercetin, a dietary flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. In this study the flavonoid quercetin was used to investigate its antioxidative effect against lindane induced oxidative stress in rats. The level of lipid peroxidation, reduced glutathione (GSH) were analysed in addition to the antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities in the liver and kidney tissue. Levels of hepatic marker enzymes in serum like Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and renal markers like serum creatinine and serum urea were estimated. Administration of Lindane induced histopathological alterations and increased levels of serum hepatic and renal markers and malondialdehyde (MDA) with a significant decrease in GSH content and CAT, SOD, GPx and GST activities. Cotreatment of quercetin along with lindane significantly decreased the lindane induced alteration in histology, serum hepatic and renal markers and MDA and also improved the cellular antioxidant status. The results show that Quercetin ameliorates Lindane induced oxidative stress in liver and kidney. The quercetin exhibited chemopreventive effect when administered along with lindane.     

Metabolic reorganization and signal transduction during estivation in the spadefoot toad

The maximal activities of 28 enzymes, representing multiple pathways of intermediary metabolism, were quantified in the brain, liver and skeletal muscle of spadefoot toads Scaphiopus couchii, comparing control toads with animals that had estivated for 2 months. Estivation-induced changes in brain enzyme activities were consistent with suppressed glycolysis and increased ketone body and amino acid catabolism. In liver, estivation resulted in reduced activities of eight enzymes representing carbohydrate, amino acid, ketone body and phosphagen metabolism, but the maximal activity of malic enzyme increased by 2.4-fold. Estivation led to a large-scale reorganization of skeletal muscle affecting most of the enzymes analyzed. Activities of enzymes of carbohydrate catabolism were generally elevated except for glycogen phosphorylase and hexokinase, whereas those of enzymes of fatty acid synthesis and ketone body metabolism were reduced. Increased glutamate dehydrogenase activities in both brain and muscle, as well as activities of other amino-acid-catabolizing enzymes in muscle, correlated with specific changes in the free amino acids pools in those tissues (reduced glutamine activity, increased glutamate, alanine and valine activities) that appear to be related to protein catabolism, for the purposes of elevating urea levels. The effects of estivation on signal transduction systems were also assessed. Total activities of protein kinases A and C (PKA and PKC) were largely unaltered in toad tissues during estivation (except for a 57% reduction in liver total PKC), but in seven organs there were strong reductions in the percentage of PKA present as the active catalytic subunit in estivating animals, and three contained a much lower percentage of membrane-bound active PKC during estivation. Activities of protein phosphatase types 1, 2A, 2B, and 2C were also frequently reduced during estivation. Overall, these results suggest that anuran estivation involves metabolic reorganization, including changing the maximal activities of key enzymes of intermediary metabolism as well as depressing the metabolic rate by suppressing signal transducing enzymes.     

MuRF1-dependent regulation of systemic carbohydrate metabolism as revealed from transgenic mouse studies

Under various pathophysiological muscle-wasting conditions, such as diabetes and starvation, a family of ubiquitin ligases, including muscle-specific RING-finger protein 1 (MuRF1), are induced to target muscle proteins for degradation via ubiquitination. We have generated transgenic mouse lines over-expressing MuRF1 in a skeletal muscle-specific fashion (MuRF1-TG mice) in an attempt to identify the in vivo targets of MuRF1. MuRF1-TG lines were viable, had normal fertility and normal muscle weights at eight weeks of age. Comparison of quadriceps from MuRF1-TG and wild type mice did not reveal elevated multi-ubiquitination of myosin as observed in human patients with muscle wasting. Instead, MuRF1-TG mice expressed lower levels of pyruvate dehydrogenase (PDH), a mitochondrial key enzyme in charge of glycolysis, and of its regulator PDK2. Furthermore, yeast two-hybrid interaction studies demonstrated the interaction of MuRF1 with PDH, PDK2, PDK4, PKM2 (all participating in glycolysis) and with phosphorylase β (PYGM) and glycogenin (both regulating glycogen metabolism). Consistent with the idea that MuRF1 may regulate carbohydrate metabolism, MuRF1-TG mice had twofold elevated insulin blood levels and lower hepatic glycogen contents. To further examine MuRF1's role for systemic carbohydrate regulation, we performed glucose tolerance tests (GTT) in wild type and MuRF1-TG mice. During GTT, MuRF1-TG mice developed striking hyperinsulinaemia and hepatic glycogen stores, that were depleted at basal levels, became rapidly replenished. Taken together, our data demonstrate that MuRF1 expression in skeletal muscle re-directs glycogen synthesis to the liver and stimulates pancreatic insulin secretion, thereby providing a regulatory feedback loop that connects skeletal muscle metabolism with the liver and the pancreas during metabolic stress.     

急性高原性低氧对三种小哺乳动物肝脏作用的比较

人工低气压舱模拟高原低氧,观察实验动物小白鼠、豚鼠及野生动物达乌尔鼠兔,在海拔5000米及8000米24小时内的几种生理效应,并与2300米海拔对照组进行了比较。发现随着海拔高度的升高:1.3种动物体重明显下降;2.肝糖原含量明显降低:小鼠、达乌尔鼠兔与豚鼠肝糖原在8000米时分别为2300米含量的62%,35%及 9%:3.小鼠、达乌尔鼠兔及豚鼠的肝脂肪累积量依次增大;4.肝蛋白质含量减少;5.SGPT与SGOT活力升高;6.肝细胞溶酶体的酸性磷酸酶与芳基硫酸脂酶活力升高。肝组织形态学观察结果与生化检测结果一致,豚鼠在8000米海拔时,肝细胞出现气球样变,脂肪变性及灶性液化性坏死等变化。综合分析,这3种动物对极度低氧的耐受性依顺序为小鼠、达乌尔鼠兔、豚鼠。     

Once a fast cod, always a fast cod: maintenance of performance hierarchies despite changing food availability in cod (Gadus morhua)

To examine whether Atlantic cod maintain constant hierarchies of sprint speeds and muscle metabolic capacities under different feeding regimes, the physiological capacities of individual cod were followed through a starvation-feeding-starvation cycle. We examined sprint speeds and maximal enzyme activities in white-muscle biopsies at each period. We measured the glycolytic enzymes, phosphofructokinase (PFK) and lactate dehydrogenase (LDH), the mitochondrial enzyme, cytochrome C oxidase (CCO), and the biosynthetic enzyme, nucleotide diphosphate kinase (NDPK). Sprint speeds were measured in a laser diode/photocell-timed raceway. As expected, the feeding regime had a marked impact on the physiological capacities of cod, but the responses differed for sprint-swimming and muscle metabolic capacities. The different enzyme activities as well the condition index generally decreased during the first starvation, improved with feeding, and fell again during the second starvation. In contrast, sprint performance improved after feeding but did not fall with the second starvation. Although both the enzyme activities and the sprint speeds showed considerable interindividual variation, sprint speeds were not significantly correlated with the enzyme activities. The hierarchy of sprint performance of the cod was maintained, regardless of the preceding feeding regime, whereas those of muscle metabolic capacities were not.     

Serine dehydratase and tyrosine aminotransferase activities increased by long-term starvation and recovery by refeeding in rainbow trout (Oncorhynchus mykiss)

Here, we study a cycle of long-term starvation followed by refeeding in relation to the kinetics of serine dehydratase (SerDH) and tyrosine aminotransferase (TyrAT) in rainbow trout (Oncorhynchus mykiss). We determine SerDH- and TyrAT- specific activity at different substrate concentrations in liver and white muscle of juvenile trout starved for 70 days and then refed for 6 hr, 32 hr, 4 days, and 9 days. SerDH showed a hyperbolic kinetic with a K(m) for L-serine of 77.07+/-8.78 mM in the liver of control trout. After 70 days of starvation, the SerDH activity at saturate substrate concentration rose 100% over control. No significant changes were found in the K(m) values of the enzyme. After refeeding, the SerDH activity declined to control values. TyrAT also showed a hyperbolic kinetic with a K(m) for L-tyrosine of 1.86+/-0.12 and 2.55+/-0.57 mM in liver and white muscle, respectively. In starved trout, TyrAT activity in liver and white muscle was about 64 and 267%, respectively, higher than control. After 9 days of refeeding, the control values recovered, although, at 6 hr of refeeding, hepatic TyrAT activity was higher than that for starvation. This work shows that SerDH and TyrAT are present in rainbow trout and that the two enzymes have regulatory functions in the catabolism of their respective amino acids in this species.     

Increases in hepatic fructose-2,6-bisphosphate level and fructose-6-phosphate,2-kinase activity in rats with ventromedial lesions of the hypothalamus

To investigate altered fructose-2,6-bisphosphate (fructose-2,6-P2) metabolism, we measured fructose-2,6-P2 levels and fructose-6-phosphate,2-kinase (fructose-6-P,2-kinase) activities in various tissues, including liver, kidney, heart, and skeletal muscle, of ventromedial hypothalamus (VMH)-lesioned rats during feeding and starvation. The plasma insulin level was 6 times or more higher in these rats than in the controls. The fructose-2,6-P2 level in liver was much greater in VMH-lesioned rats than in the controls: 15.1 +/- 2.2 nmol/g tissue versus 7.7 +/- 0.7 in the fed state, 5.3 +/- 1.1 versus 1.6 +/- 0.4 in the starved state. In kidney, heart, and skeletal muscle, fructose-2,6-P2 levels were not different between the two animal groups. The activity of hepatic fructose-6-P,2-kinase remained high after 20 h of starvation in VMH-lesioned rats, whereas it was decreased markedly in the controls. The hepatic concentration of fructose-6-phosphate was also high in VMH-lesioned rats. Both fructose-6-P,2-kinase activity and fructose-6-phosphate concentration in the liver of starved VMH-lesioned rats were comparable to those of control rats in fed conditions. These results indicate that the alteration of fructose-2,6-P2 metabolism is characteristic of liver in VMH-lesioned rats, and that the increase in hepatic fructose-2,6-P2 may activate hepatic glycolysis not only during feeding but also during starvation, leading to the enhanced lipogenesis in these obese rats.