Insulin-like growth factor-binding protein-1: an evolutionarily conserved fine tuner of insulin-like growth factor action under catabolic and stressful conditions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73293/1/j.1095-8649.2007.01606.x.pd

A Synergistic Antiobesity Effect by a Combination of Capsinoids and Cold Temperature Through Promoting Beige Adipocyte Biogenesis.

Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues

Non linear excess conductivity of Bi2_2Sr2_2Can−1_{n-1}Cun_nO2n+4+x_{2n+4+x} (n = 1,2), thin films

The suppression of excess conductivity with electric field is studied for Bi$_2$Sr$_2$Ca$_{n-1}$Cu$_n$O$_{2n+4+x}$ ($n$ = 1, 2) thin films. A pulse-probe technique is used, which allows for an estimate of the sample temperature. The characteristic electric field for fluctuations suppression is found well below the expected value for all samples. For the $n=1$ material, a scaling of the excess conductivity with electric field and temperature is obtained, similar to the scaling under strong magnetic field

The African Lungfish (\u3cem\u3eProtopterus dolloi\u3c/em\u3e): Ionoregulation and Osmoregulation in a Fish out of Water

Although urea production and metabolism in lungish have been thoroughly studied, we have little knowledge of how internal osmotic and electrolyte balance are controlled during estivation or in water. We tested the hypothesis that, compared with the body surface of teleosts, the slender African lungfish (Protopterus dolloi) body surface was relatively impermeable to water, Na+ and Cl- due to its greatly reduced gills. Accordingly, we measured the tritiated water (3H-H2O) flux in P. dolloi in water and during air exposure. In water, 3H-H2O efflux was comparable with the lowest measurements reported in freshwater teleosts, with a rate constant (K) of 17.6% body water h-1. Unidirectional ion fluxes, measured using 22Na+ and 36Cl-, indicated that Na+ and Cl- influx was more than 90% lower than values reported in most freshwater teleosts. During air exposure, a cocoon formed within 1 wk that completely covered the dorsolateral body surface. However, there were no disturbances to blood osmotic or ion (Na+, Cl-) balance, despite seven- to eightfold increases in plasma urea after 20 wk. Up to 13-fold increases in muscle urea (on a dry-weight basis) were the likely explanation for the 56% increase in muscle water content observed after 20 wk of air exposure. The possibility that muscle acted as a “water reservoir” during air exposure was supported by the 20% decline in body mass observed during subsequent reimmersion in water. This decline in body mass was equivalent to 28 mL water in a 100-g animal and was very close to the calculated net water gain (approximately 32 mL) observed during the 20-wk period of air exposure. Tritiated water and unidirectional ion fluxes on air-exposed lungfish revealed that the majority of water and ion exchange was via the ventral body surface at rates that were initially similar to aquatic rates. The 3H-H2O flux declined over time but increased upon reimmersion. We conclude that the slender lungfish body surface, including the gills, has relatively low permeability to water and ions but that the ventral surface is an important site of osmoregulation and ionoregulation. We further propose that an amphibian-like combination of ventral skin water and ion permeability, plus internal urea accumulation during air exposure, allows P. dolloi to extract water from its surroundings and to store water in the muscle when the water supply becomes limited

Wireless optogenetics protects against obesity via stimulation of non-canonical fat thermogenesis.

Cold stimuli and the subsequent activation of β-adrenergic receptor (β-AR) potently stimulate adipose tissue thermogenesis and increase whole-body energy expenditure. However, systemic activation of the β3-AR pathway inevitably increases blood pressure, a significant risk factor for cardiovascular disease, and, thus, limits its application for the treatment of obesity. To activate fat thermogenesis under tight spatiotemporal control without external stimuli, here, we report an implantable wireless optogenetic device that bypasses the β-AR pathway and triggers Ca2+ cycling selectively in adipocytes. The wireless optogenetics stimulation in the subcutaneous adipose tissue potently activates Ca2+ cycling fat thermogenesis and increases whole-body energy expenditure without cold stimuli. Significantly, the light-induced fat thermogenesis was sufficient to protect mice from diet-induced body-weight gain. The present study provides the first proof-of-concept that fat-specific cold mimetics via activating non-canonical thermogenesis protect against obesity

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of Bola3 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation via the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway

Alteration of the nucleosomal DNA path in the crystal structure of a human nucleosome core particle

Gene expression in eukaryotes depends upon positioning, mobility and packaging of nucleosomes; thus, we need the detailed information of the human nucleosome core particle (NCP) structure, which could clarify chromatin properties. Here, we report the 2.5 Å crystal structure of a human NCP. The overall structure is similar to those of other NCPs reported previously. However, the DNA path of human NCP is remarkably different from that taken within other NCPs with an identical DNA sequence. A comparison of the structural parameters between human and Xenopus laevis DNA reveals that the DNA path of human NCP consecutively shifts by 1 bp in the regions of superhelix axis location −5.0 to −2.0 and 5.0 to 7.0. This alteration of the human DNA path is caused predominantly by tight DNA–DNA contacts within the crystal. It is also likely that the conformational change in the human H2B tail induces the local alteration of the DNA path. In human NCP, the region with the altered DNA path lacks Mn(2+) ions and the B-factors of the DNA phosphate groups are substantially high. Therefore, in contrast to the histone octamer, the nucleosomal DNA is sufficiently flexible and mobile and can undergo drastic conformational changes, depending upon the environment

Focused attention meditation changes the boundary and configuration of functional networks in the brain

Research has shown that focused attention meditation not only improves our cognitive and motivational functioning (e.g., attention, mental health), it influences the way our brain networks [e.g., default mode network (DMN), fronto-parietal network (FPN), and sensory-motor network (SMN)] function and operate. However, surprisingly little attention has been paid to the possibility that meditation alters the architecture (composition) of these functional brain networks. Here, using a single-case experimental design with intensive longitudinal data, we examined the effect of mediation practice on intra-individual changes in the composition of whole-brain networks. The results showed that meditation (1) changed the community size (with a number of regions in the FPN being merged into the DMN after meditation) and (2) led to instability in the community allegiance of the regions in the FPN. These results suggest that, in addition to altering specific functional connectivity, meditation leads to reconfiguration of whole-brain network architecture. The reconfiguration of community architecture in the brain provides fruitful information about the neural mechanisms of meditation