AMPK:a nutrient and energy sensor that maintains energy homeostasis

AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability

Methods for Assessing Mitochondrial Function in Diabetes

A growing body of research is investigating the potential contribution of mitochondrial function to the etiology of type 2 diabetes. Numerous in vitro, in situ, and in vivo methodologies are available to examine various aspects of mitochondrial function, each requiring an understanding of their principles, advantages, and limitations. This review provides investigators with a critical overview of the strengths, limitations and critical experimental parameters to consider when selecting and conducting studies on mitochondrial function. In vitro (isolated mitochondria) and in situ (permeabilized cells/tissue) approaches provide direct access to the mitochondria, allowing for study of mitochondrial bioenergetics and redox function under defined substrate conditions. Several experimental parameters must be tightly controlled, including assay media, temperature, oxygen concentration, and in the case of permeabilized skeletal muscle, the contractile state of the fibers. Recently developed technology now offers the opportunity to measure oxygen consumption in intact cultured cells. Magnetic resonance spectroscopy provides the most direct way of assessing mitochondrial function in vivo with interpretations based on specific modeling approaches. The continuing rapid evolution of these technologies offers new and exciting opportunities for deciphering the potential role of mitochondrial function in the etiology and treatment of diabetes

Energy Metabolism in Uncoupling Protein 3 Gene Knockout Mice

Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined

Energy Metabolism in Uncoupling Protein 3 Gene Knockout Mice

Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined

Nutritional controlled preparation and administration of different tomato purées indicate increase of β-carotene and lycopene isoforms, and of antioxidant potential in human blood bioavailability: A pilot study

The isoforms of lycopene, carotenoids, and their derivatives including precursors of vitamin A are compounds relevant for preventing chronic degenerative diseases such as cardiovascular diseases and cancer. Tomatoes are a major source of these compounds. However, cooking and successive metabolic processes determine the bioavailability of tomatoes in human nutrition. To evaluate the effect of acute/chronic cooking procedures on the bioavailability of lycopene and carotene isoforms in human plasma, we measured the blood levels of these compounds and of the serum antioxidant potential in volunteers after a meal containing two different types of tomato sauce (rustic or strained). Using a randomized cross-over administration design, healthy volunteers were studied, and the above indicated compounds were determined by HPLC. The results indicate an increased bioavailability of the estimated compounds and of the serum antioxidant potential with both types of tomato purée and the subsequently derived sauces (the increase was greater with strained purée). This study sheds light on the content of nutrient precursors of vitamin A and other antioxidant compounds derived from tomatoes cooked with different strategies. Lastly, our study indicates that strained purée should be preferred over rustic purée

Numerical simulations on laser absorption enhancement in hybrid metallo-dielectric nanostructured targets for future nuclear astrophysics experiments

The linear electromagnetic interaction between innovative hybrid metallo-dielectric nanostructured targets and laser in visible and IR range is investigated through numerical simulations. The obtained results rely on the optimization of a target based on metallic nanowires (NWs) to enhance light absorption in the visible range of the electromagnetic spectrum. The NWs are grown within the ordered nanoholes of an alumina substrate, thus, forming a plasmonic lattice with triangular symmetry. The remaining volume of the nanoholes on top of the NWs is sealed with a transparent layer of aluminum oxide that is suitable to be chemically modified for containing about 25% of deuterium atoms. The study presented here is carried out within the framework of a scientific program named PLANETA (Plasmonic Laser Absorption on Nano-Engineered Targets) aiming at investigating new laser–matter interaction schemes in the ns domain and for nuclear fusion purposes, involving especially the D–D reaction