Adipokinetic hormone and flight metabolism in the locust

In adult male Schistocerca 20 min of tethered flight causes a halving of the haemolymph carbohydrate concentration. Injection of a proteinaceous emulsion of diglyceride 30 min before flight reduces both flight speed and carbohydrate utilisation. This effect can be overcome by the injection of trehalose immediately before the flight. If, in addition to the diglyceride, a dilute extract of the glandular lobes of the corpora cardiaca is injected immediately before flight, either with or without additional trehalose, carbohydrate utilisation is drastically reduced whereas flight speed is unaffected. It is argued that diglyceride competes with trehalose as a substrate for the flight muscles and that adipokinetic hormone from the glandular lobes of the corpora cardiaca stimulates the oxidation of diglyceride in these muscles during flight. This brings about a more complete (non-competitive) inhibition of trehalose utilisation by the flight muscles.     

Adipokinetic hormone controls lipid metabolism in adults and carbohydrate metabolism in larvae of Manduca sexta

The peptide hormone which controls activation of fat body glycogen phosphorylase in starving larvae of Manduca sexta was isolated from larval corpora cardiaca and sequenced by FAB tandem mass spectrometry. It was found to be identical with Manduca AKH. This, together with earlier observations, demonstrates that in M. sexta AKH controls glycogen phosphorylase activation in starving larvae while in adults it controls lipid mobilization during flight. Larval corpora cardiaca contain about 10 times less AKH than the corpora cardiaca of adults. The corpora cardiaca of M. sexta appear to contain only one AKH.     

Regulation of carbohydrate metabolism and flight performance by a hypertrehalosaemic hormone in the mosquito Anopheles gambiae

The role of adipokinetic hormones (AKHs) in the regulation of carbohydrate and lipid metabolism and flight performance was evaluated for females of the African malaria mosquito, Anopheles gambiae. Injection of various dosages of synthetic Anoga-AKH-I increased carbohydrate levels in the haemolymph and reduced glycogen reserves in sugar-fed females but did not affect lipid levels. Anoga-AKH-I enhanced the flight performance of both intact and decapitated sugar-fed females, during a 4 h flight period. Anoga-AKH-II had no effect on carbohydrate or lipid levels or flight performance, thus its function remains unknown. Targeted RNA-interference lowered Anoga-AKH receptor expression in sugar-fed females, consequently injections of Anoga-AKH-I failed to mobilize glycogen reserves. Taken together, these results show that a primary role for the neurohormone, Anoga-AKH-I, is to elevate trehalose levels in the haemolymph of female mosquitoes.     

Interconnection of carbohydrate and lipid metabolism in various modes of muscle activity

The activity of hexokinase and lipase has been determined in skeletal muscles of different metabolic types and adipose tissue of untrained albino rats during two variations of predominant aerobic physical exercise: long-term swimming and long-term swimming including short-term loads (20 s) of maximal intensity (acceleration). Muscle and liver glycogen depletion, serum lactate, glucose and free fatty acids concentrations are also investigated. It is shown that long-term swimming (first variation) has promoted a decrease of both enzymatic activities in muscle fibres and an increase in lipolytic activity of the adipose tissue. During the physical exercise with the acceleration an increase in hexokinase activity occurs in response to 20 min swimming, with its maximal decrease in response to 40 min of exercise. Activity of lipase in slow-twitch oxidative fibres of soleus and in the adipose tissue increases from 20 min to the end of the exercise. Depletion of glycogen in the muscles and liver is determined in fast-twitch oxidative-glycolytic fibres and in the liver in two types of exercises, being more significant in muscles after exercise with accelerations. Concentrations of serum lactate, glucose and free fatty acids remain unchanged after both variations of swimming. So, it may be concluded that acute adaptation to the predominant aerobic physical exercise with activity under short-term loads of maximal intensity has induced a rise of the capacity of oxidative muscles to utilise endogenous and exogenous carbohydrate and lipid reserves.     

Chromium in carbohydrate and lipid metabolism

 Since the discovery in the 1950s that mammals have a nutritional requirement for chromium, the biological function of chromium has been sought. Candidates for the naturally-occurring biologically active form of chromium have been proposed, but, until recently, all have been shown to be artifacts. Recent studies examining the properties of the oligopeptide low-molecular-weight chromium-binding substance (LMWCr) suggest that this material may have a role in carbohydrate and lipid metabolism as part of a novel insulin-signaling amplification mechanism and may have implications in the treatment of diabetes and related conditions. Received: 24 March 1997 / Accepted: 9 September 1997     

Role of fatty acid-binding protein in lipid metabolism of insect flight muscle

Since insect flight muscles are among the most active muscles in nature, their extremely high rates of fuel supply and oxidation pose interesting physiological problems. Long-distance flights of species like locusts and hawkmoths are fueled through fatty acid oxidation. The lipid substrate is transported as diacylglycerol in the blood, employing a unique and efficient lipoprotein shuttle system. Following diacylglycerol hydrolysis by a flight muscle lipoprotein lipase, the liberated fatty acids are ultimately oxidized in the mitochondria. Locust flight muscle cytoplasm contains an abundant fatty acid-binding protein (FABP). The flight muscle FABP ofLocusta migratoria is a 15 kDa protein with an isoelectric point of 5.8, binding fatty acids in a 1:1 molar stoichiometric ratio. Binding affinity of the FABP for longchain fatty acids (apparent dissociation constant K_d=5.21±0.16 M) is however markedly lower than that of mammalian FABPs. The NH₂-terminal amino acid sequence shares structural homologies with two insect FABPs recently purified from hawkmoth midgut, as well as with mammalian FABPs. In contrast to all other isolated FABPs, the NH₂ terminus of locust flight muscle FABP appeared not to be acetylated. During development of the insect, a marked increase in fatty acid binding capacity of flight muscle homogenate was measured, along with similar increases in both fatty acid oxidation capacity and citrate synthase activity. Although considerable circumstantial evidence would support a function of locust flight muscle FABP in intracellular uptake and transport of fatty acids, the finding of another extremely well-flying migratory insect, the hawkmothAcherontia atropos, which employs the same lipoprotein shuttle system, however contains relatively very low amounts of FABP in its flight muscles, renders the proposed function of FABP in insect flight muscles questionable.     

Ratio between carbohydrate and lipid metabolism in muscle cell energy metabolism during ATPase loading. Mathematical model

A mathematical model is proposed to describe the interaction between glycolysis, the Krebs cycle and 3-oxidation (beta OX). The model incorporates the activations of phosphofructokinase by AMP and of isocitrate dehydrogenase by ADP as well as the inhibitions of citrate synthase by citrate, of acyl CoA synthase by excess CoAsAcyl, of pyruvate dehydrogenase (PDH) and the beta OX helix by the products CoAsAc and NADH. These regulations have been shown to provide consecutive triggering of the fatty acid and glucose oxidation systems with an increase in the ATPase load, the beta OX of fatty acids being a major source of energy at small loads. The steady state rates of glycolysis and PDH-reaction begin to increase at larger loads when the rate of beta OX is close to its maximum value. At maximum ATPase loads, the glucose oxidation accounts for more than 80% of the total energy production. Under limited fatty acid supply, the transfer to glucose oxidation gives rise to a region of the ATPase loads, where in the steady state levels of NADH and CoAsAc increase with load.     

The influence of flight on the phospholipid metabolism in insect flight muscle

Males of the American cockroach, Periplaneta americana, received an injection of 32P-orthophosphates and the specific activity of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) was determined after 120 min of in vivo incorporation. If the insects were forced to fly for 10 min immediately before the end of the experiment, the specific activity (S.A.) of PC and PE was lowered by 34.3 and 31.0%, respectively, that of PI by 17.5%. If the animals were allowed to rest for 10 min after cessation of flight, the S.A. of PC and PE did not differ significantly from the controls, whereas that of PI rose by 91.0% above the control value. These effects cannot be due to changes in precursor labelling (glycerophosphate and phosphoarginine were measured) and reflect changes in the rate of phospholipid biosynthesis. The possibility is discussed that mechanisms regulating the rate of phospholipid biosynthesis are involved.     

Adipose triglyceride lipase regulation of skeletal muscle lipid metabolism and insulin responsiveness

Adipose triglyceride lipase (ATGL) is important for triglyceride (TG) metabolism in adipose tissue, and ATGL-null mice show increased adiposity. Given the apparent importance of ATGL in TG metabolism and the association of lipid deposition with insulin resistance, we examined the role of ATGL in regulating skeletal muscle lipid metabolism and insulin-stimulated glucose disposal. ATGL expression in myotubes was reduced by small interfering RNA and increased with a retrovirus encoding GFP-HA-ATGL. ATGL was also overexpressed in rats by in vivo electrotransfer. ATGL was down-regulated in skeletal muscle of obese, insulin-resistant mice and negatively correlated with intramyocellular TG levels. ATGL small interfering RNA in myotubes reduced TG hydrolase activity and increased TG content, whereas ATGL overexpression induced the reciprocal response, indicating that ATGL is an essential TG lipase in skeletal muscle. ATGL overexpression in myotubes increased the oxidation of fatty acid liberated from TG and diglyceride and ceramide contents. These responses in cells were largely recapitulated in rats overexpressing ATGL. When ATGL protein expression and TG hydrolase activity in obese, insulin-resistant rats were restored to levels observed in lean rats, TG content was reduced; however, the insulin resistance induced by the high-fat diet persisted. In conclusion, ATGL TG hydrolysis in skeletal muscle is a critical determinant of lipid metabolism and storage. Although ATGL content and TG hydrolase activity are decreased in obese, insulin-resistant phenotypes, overexpression does not rescue the condition, indicating reduced ATGL is unlikely to be a primary cause of obesity-associated insulin resistance.     

Effect of histamine H1-receptor antagonist on the regulation of carbohydrate and lipid metabolism in rat liver

In order to elucidate the role of histamine in the liver, we studied the effect of a histamine H1-receptor antagonist on the carbohydrate and lipid metabolism in the rat liver. The administration of the H1-receptor antagonist decreased significantly the contents of glycogen and malonyl-CoA in the liver. However, it did not affect the levels of serum glucose and free fatty acid. These results suggest that histamine may play a part in the regulation of metabolism of carbohydrates and lipids in the liver.     

昆虫糖脂代谢研究进展

肥胖症和糖尿病的日趋流行已经成为世界范围内的公共健康问题,其病因主要在于体内血糖/血脂含量升高引起的能量代谢紊乱。大量的证据表明,昆虫可以作为研究人类代谢疾病的理想模型,它不仅能合成与哺乳动物同源的糖脂代谢相关激素(如胰岛素样肽和脂动激素),而且还具有进化保守的代谢信号通路(如雷帕霉素靶蛋白信号通路)及相关器官与组织(如中肠和脂肪体)。本文主要介绍了昆虫糖脂代谢的过程与调控机制,重点涉及脂肪体和绛色细胞的生理功能、胰岛素样肽/脂动激素对血糖的拮抗调节、参与营养物质代谢的胰岛素-胰岛素样生长因子信号通路以及与类固醇激素合成相关的胆固醇代谢等内容,并结合最新研究成果对黑腹果蝇Drosophila melanogaster糖脂代谢相关基因及其功能进行了总结,以期为昆虫生理学和人类代谢疾病研究提供参考。     

Cell structure and the metabolism of insect flight muscle

The biochemical properties of insect flight muscle were investigated to ascertain the mechanisms whereby energy is made available for the contractile processes. It was found: 1. The endogenous respiration of muscle homogenates was diminished by starving the flies. The substrate for this respiration was probably glycogen. 2. To obtain the maximal rate of oxidation of glucose, the homogenate had to be fortified with inorganic phosphate, Mg ions, ATP, and cytochrome c. The nucleotides, AMP and ADP, were not as effective as ATP. The addition of DPN or TPN was not necessary for this system. 3. Flight muscle homogenates oxidized glycogen, some sugars, and amino acids, as well as the intermediates of the glycolytic and tricarboxylic acid cycles. Other evidence demonstrated the substrate specificity of the muscle. 4. By centrifugation, the muscle homogenate was divided into two fractions: one, a soluble fraction representing the sarcoplasm; the other, the particulate fraction which contained the fibrils and the sarcosomes. 5. The particulate fraction, alone, oxidized all the citric acid cycle intermediates, alpha-glycerophosphate, phosphopyruvate, and the amino acids, glutamic, proline, and cysteine. Regardless of the substrate, no oxygen uptake was found with the sarcoplasm by itself. 6. A recombination of the sarcoplasm and the particulate component was required for the oxidation of glycogen, the hexoses, and all the phosphorylated intermediates of glycolysis, except phosphopyruvate. 7. Isolated mitochondria accounted for all the enzymatic activity of the particulate fraction. These results demonstrate that the enzymes of intermediate metabolism are localized in the sarcoplasm or sarcosomes. The third cytological entity, the myofibrils, plays no role in the energy-providing scheme. From a functional viewpoint, the sarcoplasm and the mitochondria, in combination, furnish the energy for the actomyosin contraction. The results are discussed in relation to analogous findings in other insects and vertebrates.     

Effects of modulation of glycerol kinase expression on lipid and carbohydrate metabolism in human muscle cells.

Glycerol is taken up by human muscle in vivo and incorporated into lipids, but little is known about regulation of glycerol metabolism in this tissue. In this study, we have analyzed the role of glycerol kinase (GlK) in the regulation of glycerol metabolism in primary cultured human muscle cells. Isolated human muscle cells exhibited lower GlK activity than fresh muscle explants, but the activity in cultured cells was increased by exposure to insulin. [U-(14)C]Glycerol was incorporated into cellular phospholipids and triacylglycerides (TAGs), but little or no increase in TAG content or lactate release was observed in response to changes in the medium glycerol concentration. Adenovirus-mediated delivery of the Escherichia coli GlK gene (AdCMV-GlK) into muscle cells caused a 30-fold increase in GlK activity, which was associated with a marked rise in the labeling of phospholipid or TAG from [U-(14)C]glycerol compared with controls. Moreover, GlK overexpression caused [U-(14)C]glycerol to be incorporated into glycogen, which was dependent on the activation of glycogen synthase. Co-incubation of AdCMV-GlK-treated muscle cells with glycerol and oleate resulted in a large accumulation of TAG and an increase in lactate production. We conclude that GlK is the limiting step in muscle cell glycerol metabolism. Glycerol 3-phosphate is readily used for TAG synthesis but can also be diverted to form glycolytic intermediates that are in turn converted to glycogen or lactate. Given the high levels of glycerol in muscle interstitial fluid, these finding suggest that changes in GlK activity in muscle can exert important influences on fuel deposition in this tissue.