SUMMARY Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis.

The magnetic field signature obtained by Cassini during its first close encounter with Titan on 26 October 2004 is presented and explained in terms of an advanced model. Titan was inside the saturnian magnetosphere. A magnetic field minimum before closest approach marked Cassini's entry into the magnetic ionopause layer. Cassini then left the northern and entered the southern magnetic tail lobe. The magnetic field before and after the encounter was approximately constant for approximately 20 Titan radii, but the field orientation changed exactly at the location of Titan's orbit. No evidence of an internal magnetic field at Titan was detected.

[1] The first close Titan encounters TA, TB, and T3 of the Cassini mission at almost the same Saturnian local time $1030 and in the same spatial region downstream of Titan have enabled us to study the formation of the tail of its induced magnetosphere. The study is based on magnetic field and electron plasma observations as well as threedimensional modeling. Our most important findings are the following: (1) No crossings of a bow shock of Titan were observed, and all encounters occurred at high plasma b > 1 for transsonic and trans-Alfvénic Mach numbers. (2) The magnetic draping signature of the induced magnetosphere often shows a sharp outer boundary called the draping boundary (DB) in the near-tail region. (3) The DB is often occurring as a discontinuity in magnetic field spatial derivatives, and therefore the DB is a discontinuity in the spatial distribution of plasma currents. (4) Perpendicular to the incident flow direction the DB shows an approximately elliptic cross section elongated along the incident magnetic field direction and a displacement toward the Sun. (5) We argue that the DB in the magnetic tail region corresponds to the boundary of a structure which is analogous to an Alfvén wing at very small b and in our case of larger b contains Alfvénic and slow mode features. It forms a tail like a delta wing in aerodynamics. (6) For the two less disturbed flybys, TA and T3, a polarity reversal layer has been observed with thicknesses of $320 km and $230 km, respectively.

Highlights d Thyroid hormone induces browning independent of sympathetic nervous system through TRb d Despite high UCP1, the beige fat lacks adrenergic input and is inactive d Thyroid hormone's metabolic and thermogenic effects are maintained in UCP1 knockout mice d Thyroid hormone induces hyperthermia and elevates the body temperature setpoint

Purpose: The aim of this study was to investigate the relationship between the in vivo derived kinetic parameters of 3 ¶-deoxy-3 ¶-

Focal cerebral ischemia elicits strong inflammatory responses involving activation of resident microglia and recruitment of monocytes/macrophages. These cells express peripheral benzodiazepine receptors (PBRs) and can be visualized by positron emission tomography (PET) using [ 11 C]PK11195 that selectively binds to PBRs. Earlier research suggests that transient ischemia in rats induces increased [11 C]PK11195 binding within the infarct core. In this study, we investigated the expression of PBRs during permanent ischemia in rats. Permanent cerebral ischemia was induced by injection of macrospheres into the middle cerebral artery. Multimodal imaging 7 days after ischemia comprised (1) 18 F]FDG metabolic rate constant with accumulated activated microglia and macrophages. These results suggest that after permanent focal ischemia, neuroinflammation occurring in the normoperfused peri-infarct zone goes along with increased energy demand, therefore extending the tissue at risk to areas adjacent to the infarct.

High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity.

Neural stem cells reside in two major niches in the adult brain [i.e., the subventricular zone (SVZ) and the dentate gyrus of the hippocampus]. Insults to the brain such as cerebral ischemia result in a physiological mobilization of endogenous neural stem cells. Since recent studies showed that pharmacological stimulation can be used to expand the endogenous neural stem cell niche, hope has been raised to enhance the brain's own regenerative capacity. For the evaluation of such novel therapeutic approaches, longitudinal and intraindividual monitoring of the endogenous neural stem cell niche would be required. However, to date no conclusive imaging technique has been established. We used positron emission tomography (PET) and the radiotracer 3Ј-deoxy-3Ј-[