Emerging debates and resolutions in brown adipose tissue research.

Until two decades ago, brown adipose tissue (BAT) was studied primarily as a thermogenic organ of small rodents in the context of cold adaptation. The discovery of functional human BAT has opened new opportunities to understand its physiological role in energy balance and therapeutic applications for metabolic disorders. Significantly, the role of BAT extends far beyond thermogenesis, including glucose and lipid homeostasis, by releasing mediators that communicate with other cells and organs.

Non-invasive mapping of brown adipose tissue activity with magnetic resonance imaging.

Thermogenic brown adipose tissue (BAT) has a positive impact on whole-body metabolism. However, in vivo mapping of BAT activity typically relies on techniques involving ionizing radiation, such as [F]fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) and computed tomography (CT). Here we report a noninvasive metabolic magnetic resonance imaging (MRI) approach based on creatine chemical exchange saturation transfer (Cr-CEST) contrast to assess in vivo BAT activity in rodents and humans.

Transform-Limited Photon Emission from a Lead-Vacancy Center in Diamond above 10 K.

Transform-limited photon emission from quantum emitters is essential for high-fidelity entanglement generation. In this Letter, we report the coherent optical property of a single negatively charged lead-vacancy (PbV) center in diamond. Photoluminescence excitation measurements reveal stable fluorescence with a linewidth of 39 MHz at 6 K, close to the transform limit estimated from the lifetime measurement.

Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB.

That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1). However, germline Ucp1 mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption.

Revealing the Origin of Fast Delayed Fluorescence in a Donor Functionalized Bisterpyridine.

A new carbazole-substituted bisterpyridine with pronounced delayed fluorescence is presented. While the molecular donor-acceptor-donor design suggests the origin of this to be thermally activated delayed fluorescence (TADF), results from various photophysical characterizations, OLED characteristics, temperature-dependent NMR spectroscopy, and DFT calculations all point against the involvement of triplet states. The molecule exhibits blue emission at about 440 nm with two or more fast decay channels in the lower nanosecond range in both solution and thin films.

Promoting metabolic inefficiency for metabolic disease.

Recent advances in pharmacotherapies that promote appetite suppression have shown remarkable weight loss. Therapies targeting energy expenditure lag behind, and as such none have yet been identified to be safe and efficacious for sustaining negative energy balance toward weight loss. Multiple energy dissipating pathways have been identified in adipose tissue and muscle.

ADRA1A-Gα signalling potentiates adipocyte thermogenesis through CKB and TNAP.

Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis. Aside from cAMP signalling downstream of β-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α-adrenergic receptor (AR) and β-AR signalling induces the expression of thermogenic genes of the futile creatine cycle, and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo.

The timing of eating controls energy use.

Synchronizing food intake with the body clock boosts thermogenesis and limits obesity.

Ionization potentials of Mg ( = 7-56) clusters formed by spontaneous collapse of magnesium foam in helium nanodroplets.

The ionization potentials of magnesium clusters (Mg, = 7-56) are determined by doping ultracold helium nanodroplets (He, ≈ 52 000) with Mg atoms. Inspecting the particle size distributions resulting from non-resonant, short-wavelength, single-photon ionization gives evidence that beyond a certain ensemble size, the developing foam structure undergoes a spontaneous collapse on the way to the laser interaction region. As a result, hot Mg clusters form in the relaxation process.

A brown fat-selective mechanism of mitochondrial calcium import?

In this issue of Cell Metabolism, Xue et al. propose that the mitochondrial calcium uniporter (MCU) binds uncoupling protein 1 (UCP1) via the MCU regulator (EMRE) to form a protein complex that the authors term the "thermoporter." Through gain- and loss-of-function experiments, the authors infer that the thermoporter promotes calcium influx into the mitochondrial matrix to enhance NADH production, which supports thermogenesis in brown adipose tissue (BAT).

Mitochondrial uncouplers induce proton leak by activating AAC and UCP1.

Mitochondria generate heat due to H leak (I) across their inner membrane. I results from the action of long-chain fatty acids on uncoupling protein 1 (UCP1) in brown fat and ADP/ATP carrier (AAC) in other tissues, but the underlying mechanism is poorly understood. As evidence of pharmacological activators of I through UCP1 and AAC is lacking, I is induced by protonophores such as 2,4-dinitrophenol (DNP) and cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP).

Calcium burns beige.

In this issue of Journal of Experimental Medicine, Yin et al. (2022. J.

Creatine transport and creatine kinase activity is required for CD8 T cell immunity.

The factors that promote T cell expansion are not fully known. Creatine is an abundant circulating metabolite that has recently been implicated in T cell function; however, its cell-autonomous role in immune-cell function is unknown. Here, we show that creatine supports cell-intrinsic CD8 T cell homeostasis.

Measurement of Futile Creatine Cycling Using Respirometry.

Thermogenic adipose tissue plays a vital function in regulating whole-body energy expenditure and nutrient homeostasis due to its capacity to dissipate chemical energy as heat, in a process called non-shivering thermogenesis. A reduction of creatine levels in adipocytes impairs thermogenic capacity and promotes diet-induced obesityKazak et al, Cell 163, 643-55, 2015; Kazak et al, Cell Metab 26, 660-671.e3, 2017; Kazak et al, Nat Metab 1, 360-370, 2019).

Phase-of-the-Phase Electron Momentum Spectroscopy on Single Metal Atoms in Helium Nanodroplets.

Magnesium atoms fully embedded in helium nanodroplets are exposed to two-color laser pulses, which trigger multiphoton above-threshold ionization (ATI). This allows exemplary study of the contribution of a dense, neutral, and finite medium on single electron propagation. The angular-resolved photoelectron spectra show striking differences with respect to results obtained on free atoms.

Neutrophil oxidative stress mediates obesity-associated vascular dysfunction and metastatic transmigration.

Metastasis is the leading cause of cancer-related deaths, and obesity is associated with increased breast cancer (BC) metastasis. Preclinical studies have shown that obese adipose tissue induces lung neutrophilia associated with enhanced BC metastasis to this site. Here we show that obesity leads to neutrophil-dependent impairment of vascular integrity through loss of endothelial adhesions, enabling cancer cell extravasation into the lung.

Creatine promotes metastatic dissemination.

The molecular regulation of cancer metastasis is not fully understood. In this issue of Cell Metabolism, Zhang et al. (2021) discover that creatine promotes cancer metastasis in mice by promoting activation of the MPS1-Smad2/3 axis.

Balancing energy demand and production by mitochondrial trafficking of RHEB.

In this issue of Developmental Cell,Yang et al. (2021) discover that, RHEB traffics to mitochondria to promote energy production by stimulating pyruvate dehydrogenase to convert pyruvate to acetyl-CoA.

Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer.

Obesity is a major risk factor for adverse outcomes in breast cancer; however, the underlying molecular mechanisms have not been elucidated. To investigate the role of crosstalk between mammary adipocytes and neoplastic cells in the tumor microenvironment (TME), we performed transcriptomic analysis of cancer cells and adjacent adipose tissue in a murine model of obesity-accelerated breast cancer and identified glycine amidinotransferase (Gatm) in adipocytes and Acsbg1 in cancer cells as required for obesity-driven tumor progression. Gatm is the rate-limiting enzyme in creatine biosynthesis, and deletion in adipocytes attenuated obesity-driven tumor growth.

No evidence for brown adipose tissue activation after creatine supplementation in adult vegetarians.

Creatine availability in adipose tissue has been shown to have profound effects on thermogenesis and energy balance in mice. However, whether dietary creatine supplementation affects brown adipose tissue (BAT) activation in humans is unclear. In the present study, we report the results of a double-blind, randomized, placebo-controlled, cross-over trial (NCT04086381) in which 14 young, healthy, vegetarian adults, who are characterized by low creatine levels, received 20 g of creatine monohydrate per day or placebo.

Temporal Development of a Laser-Induced Helium Nanoplasma Measured through Auger Emission and Above-Threshold Ionization.

Femtosecond pump-probe electron and ion spectroscopy is applied to study the development of a helium nanoplasma up to the nanosecond timescale. Electrons, bound by the deep confining mean-field potential, are elevated toward the vacuum level in the nanoplasma expansion. Subsequent electron recombination gives rise to transitions between He^{+} states, resulting in autoionization.