Invariant natural killer T cells in adipose tissue: novel regulators of immune-mediated metabolic disease

Adipose tissue (AT) represents a microenvironment where intersection takes place between immune processes and metabolic pathways. A variety of immune cells have been characterized in AT over the past decades, with the most recent addition of invariant natural killer T (iNKT) cells. As members of the T cell family, iNKT cells represent a subset that exhibits both innate and adaptive characteristics and directs ensuing immune responses. In disease conditions, iNKT cells have established roles that include disorders in the autoimmune spectrum in malignancies and infectious diseases. Recent work supports a role for iNKT cells in the maintenance of AT homeostasis through both immune and metabolic pathways. The deficiency of iNKT cells can result in AT metabolic disruptions and insulin resistance. In this review, we summarize recent work on iNKT cells in immune regulation, with an emphasis on AT-resident iNKT cells, and identify the potential mechanisms by which adipocytes can mediate iNKT cell activity.     

Inhibition of phosphoenolpyruvate carboxykinase by 6-phosphogluconate in rat liver

Various concentrations of 6-phosphogluconate inhibit rat liver phosphoenolpyruvate carboxykinase activity. 0.04 mM 6-phosphogluconate, which is the concentration found in vivo, caused a 50% inhibition of 6-phosphoenolpyruvate carboxykinase activity. 6-Phosphogluconate lowered the Vmax of the enzyme and increased the concentration of phosphoenolpyruvate required to achieve one-half of the maximum velocity. The role of 6-phosphogluconate as a regulator of the coordination of fluxes through three metabolic pathways is discussed.     

Inhibition of phosphoenolpyruvate carboxykinase by 6-phosphogluconate in rat liver

Summary Various concentrations of 6-phosphogluconate inhibit rat liver phosphoenolpyruvate carboxykinase activity. 0.04 mM 6-phosphogluconate, which is the concentration found in vivo, caused a 50% inhibition of 6-phosphoenolpyruvate carboxykinase activity. 6-Phosphogluconate lowered the V_max of the enzyme and increased the concentration of phosphoenolpyruvate required to achieve one-half of the maximum velocity. The role of 6-phosphogluconate as a regulator of the coordination of fluxes through three metabolic pathways is discussed.     

Techniques simultanées de mesures: CO2(C14O2) élimination urinaire et activité motrice chez la souris dans l'expérimentation métabolique des amphétamines

Summary An apparatus which permits simultaneous measuring of the expiratory CO₂, the amount of C¹⁴O₂ and O₂ in metabolic studies of labelled drugs, is described. The urine and faeces are collected in the metabolic cage of this apparatus. Furthermore, the motor activity of the animal can be measured and recorded.     

Synchronization of deposition of daily growth layers in the cuticle of the cockroachBlaberus fuscus by gating of moult

Summary InBlaberus fuscus, combined light/dark-warm/cold cycles induce a rhythm of moulting. Most of the moults take place in the middle of the dark cold phases. Because of a stable phase-relation between moulting time and endocuticle growth rhythm, the latter is synchronized with the environmental cycles, too; lamellated layers are deposited during the light warm phases, which correspond to the time of resting of the cockroaches. Therefore, the cuticle growth is internally synchronized with rhythmic locomotory activity and metabolic rhythms.     

Patterns of neuroglial proliferation in spinal cord white matter following exposure to ionizing radiation

Summary X-irradiation temporarily decreases the proliferative activity of neuroglia in immature rat spinal cord. Later, the proliferative activity in these irradiated regions surpasses that noted in control rats. Areas adjacent to the irradiated region have a greater than normal percentage of labelled neuroglia and may also be a source for neuroglia which re-populate the irradiated zone.Acknowledgments. Sincere thanks to Ms Jane Leiting for her assistance in doing the cell counts and to Mr Napoleon Phillips for preparing the autoradiographs. Supported by USPHS grant NS 04761.     

The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?

Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported.     

Effects of palytoxin on the electrical activity of dog and rabbit heart.

Reversible effects of palytoxin, extracted from colonies of the soft coral Palythoa caribaeorum, are described. There is a decrease of both membrane resting potential and overshoot during activity. Rise time of the action potential is prolonged, while repolarization is shortened. The electrical events resemble those seen with metabolic poisons.     

Involutive morphological modifications in the rat adrenal glomerular zone after a low-sodium diet

Summary We have studied glomerular zone involution in the rat's adrenal gland after a period of hyperfunction brought about by a low-sodium diet. The changes observed in this zone affect those organoids that are more directly involved in steroid genesis; mitochondria, smooth endoplasmic reticulum and liposomes. The Golgi complexes appear very developed, often, showing, a positive acid phosphatase activity. Lysosomes suffered a considerable increase in their number, and carried out their digestive function on liposomes. All those changes discussed here are seen as an accomodation of this zone to the new normofunctional situation.     

Activity of specific collagenases in developing granulomatous tissues]

Specific collagenases are activated rapidly in inflamed tissues. This activity reaches a higher level in acute inflammation than in chronic inflammation. It appears to be related to an increased metabolic activity of the local fibroblasts.     

Lipid sensing and lipid sensors

Translation of nutrient stimuli through intracellular signaling is important for adaptation and regulation of metabolic processes, while deregulation by either genetic or environmental factors predisposes towards the development of metabolic disorders. Besides providing energy, fatty acids act as prominent signaling molecules by altering cell membrane structures, affecting the lipid modification status of proteins, and by modulating ligand-activated nuclear receptor activity. Given their highly hydrophobic nature, fatty acids in the aqueous intracellular compartment are bound to small intracellular lipid binding proteins which function as intracellular carriers of these hydrophobic components. This review describes recent advances in identifying intracellular pathways for cytosolic fatty acid signaling through ligand activated receptors by means of small intracellular lipid binding proteins. The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders.     

Activity alterations of metabolic enzymes in the anterior pituitary of female rats during acute and chronic starvation,as well as after refeeding

Summary The activity of glycolysis and hexose monophosphate shunt decreases while the activity of some oxydative enzymes and acid phosphatase increases in the anterior pituitary of adult female rats during starvation. The alterations depend on the severity of starvation. The polypeptide hormone production also decreases. A close relationship exists between the metabolic activity of the gland and its endocrine function.     

Coated vesicles in the rat adrenal glomerular zone after a low-sodium diet.

In rats subjected to a low-sodium diet, a great activity was observed of the coated vesicles at Golgi complex and cell surfaces of glomerular adrenal zone. These findings are related to the function of these organoids in the uptake and transport of necessary substances under stimulating conditions of the zone.     

Coated vesicles in the rat adrenal glomerular zone after a low-sodium diet

Summary In rats subjected to a low-sodium diet, a great activity was observed of the coated vesicles at Golgi complex and cell surfaces of glomerular adrenal zone. These findings are related to the function of these organoids in the uptake and transport of necessary substances under stimulating conditions of the zone.     

Melatonin,mitochondria, and the metabolic syndrome

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.     

The regulation of trehalose metabolism in insects

Trehalose is a non-reducing disaccharide comprising two glucose molecules. It is present in high concentration as the main haemolymph (blood) sugar in insects. The synthesis of trehalose in the fat body (an organ analogous in function to a combination of liver and adipose tissue in vertebrates) is stimulated by neuropeptides (hypertrehalosaemic hormones), released from the corpora cardiaca, a neurohaemal organ associated with the brain. The peptides cause a decrease in the content of fructose 2,6-bisphosphate in fat body cells. Fructose 2,6-bisphosphate, acting synergistically with AMP, is a potent activator of the glycolytic enzyme 6-phosphofructokinase-1 and a strong inhibitor of the gluconeogenic enzyme fructose 1,6-bisphosphatase. This indicates that fructose 2,6-bisphosphate is a key metabolic signal in the regulation of trehalose synthesis in insects. Trehalose is hydrolysed by trehalase (E.C. 3.2.1.28). The activity of this enzyme is regulated in flight muscle, but the mechanism by which this is achieved is unknown. Trehalase from locust, flight muscle is a glycoprotein bound to membranes of the microsomal fraction. The enzyme can be activated by detergents in vitro and by short flight intervals in vivo, which indicates that changes in the membrane environment modulate trehalase activity under physiological conditions.     

Séparation sur séphadex G 100 de facteurs mucicriniques et mucimitiginiques à partir d'un extrait de muqueuse duodénale

Summary The mucicrin stimulating the hexosamine gastrointestinal secretion and extracted from porcine duodenum, was concentrated in the zone 7 using sephadex G 100. The molecular weight of 4000–5000 corresponds to this zone. An opposite activity was detected in zone 3. The factor from digestive mucous origin being able to diminish the hexosamine gastric secretion and not influencing the arterial pressure was called mucimitigin. The molecular weight of about 35000 corresponds to this factor.