Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics

Methodological advances in imaging intravital axonal transport.

Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer's disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation. A number of intravital techniques originally developed for studying diverse biological events have recently been adapted to monitor axonal transport in real-time in a range of live organisms and are providing novel insight into this dynamic process. Here, we highlight these methodological advances in intravital imaging of axonal transport, outlining key strengths and limitations while discussing findings, possible improvements, and outstanding questions

The beta secretase BACE1 regulates the expression of insulin receptor in the liver

Insulin receptor (IR) plays a key role in the control of glucose homeostasis; however, the regulation of its cellular expression remains poorly understood. Here we show that the amount of biologically active IR is regulated by the cleavage of its ectodomain, by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), in a glucose concentration-dependent manner. In vivo studies demonstrate that BACE1 regulates the amount of IR and insulin signaling in the liver. During diabetes, BACE1-dependent cleavage of IR is increased and the amount of IR in the liver is reduced, whereas infusion of a BACE1 inhibitor partially restores liver IR. We suggest the potential use of BACE1 inhibitors to enhance insulin signaling during diabetes. Additionally, we show that plasma levels of cleaved IR reflect IR isoform A expression levels in liver tumors, which prompts us to propose that the measurement of circulating cleaved IR may assist hepatic cancer detection and management

Acclimation of poplar trees to heavy metals in polluted habitats: I. Carbohydrate metabolism in fine roots of Populus deltoides

Concentrations of total nonstructural carbohydrates (TNC), soluble carbohydrates, starch, sucrose, glucose, fructose, raffinose, galactose, stachyose, mannitol and specific activities of soluble acid (AI) and neutral (NI) invertases, sucrose synthase (SuSy), hexokinase (HK), fructokinase (FK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glucose 6-phosphate dehydrogenase (G6PDH) were analyzed in fine roots of Populus deltoides Bartr. ex Marsh growing at a polluted site (near copper smelters) and a control site (free from heavy pollution). Also chemical properties of the soil from both sites were assessed. In comparison with the control, fine roots from the polluted site contained greater concentrations of TNC, soluble sugars, starch and sucrose but less hexoses, so they had higher values of sucrolysis index (sucrose/hexoses). The activity of AI, NI and SuSy declined insignificantly, while specific activities of HK, FK, GAPDH and G6PDH were significantly inhibited. The results suggest that a long-term heavy metal stress leads to an accumulation of carbohydrates and altering activities of glycolysis and the oxidative pentose phosphate pathway in fine roots

Social Transmission of Food Preference in C57BL/6 Mice

status: publishe

Photochemical activity, photosynthetic pigments and carbohydrates in poplar leaves fumigated with sulphur dioxide

The purpose of this study was to assess the influence of SO2 on photosynthetic apparatus and the level of total nonstructural carbohydrates (TNC) in developing and mature leaves of poplar (Populus deltoides). Photosynthetic apparatus was evaluated on the basis of fluorescence parameters (Fv/Fm, OPSII, qP and Rfd) and photosynthetic pigments (chlorophylls and carotenoids). Cuttings of poplar were exposed to 0.25 ppm of SO2 at 25°C and 200-300 mmol m-2s-1 PAR for 6 hours daily during 5 days in a fumigation chamber. The fumigation did not produce any significant differences in fluorescence parameters in neither developing nor mature leaves. In some mature leaves the concentration of pigments increased under the influence of SO2. Soluble carbohydrates decreased significantly both in developing and mature leaves and this was accompanied with an increase in starch accumulation. We suggest that Populus deltoides is a species tolerant to sulphur dioxide and the used SO2 dosage did not significantly impair the light reactions of photosynthesis, but it disturbed the accumulation of starch and the utilization of soluble carbohydrates in plants exposed to SO2