12 research outputs found
Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis
Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of beta-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gscoupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.Diabetes mellitus: pathophysiological changes and therap
Electron-ion and ion-ion reaction rate coefficients at low altitudes during a PCA event
Based on experimental data from several ESRO PCA rocket flights some considerations are presented regarding the mean values of the electron-ion dissociative recombination coefficient (αd) and the ion-ion neutralization coefficient (αi). The estimates yield values for αd = 10−5 cm3 sec−1 for heights between 60 and 67 km. The data indicate that αi is smaller than αd by a factor of 100
Baseline pressure-pain tolerance threshold predicts the clinical outcome of a weight loss intervention in obese knee OA patients: a prospective cohort study
The association between pressure-pain tolerance threshold and local and/or systemic inflammation in obese knee osteoarthritis patients: a cross-sectional study
Assessment of Advanced Dispatching Measures for Recovering Disrupted Railway Traffic Situations
Extreme mobility enhancement of two-dimensional electron gases at oxide interfaces by charge-transfer-induced modulation doping
Two-dimensional electron gases (2DEGs) formed at the interface of insulating complex oxides promise the development of all-oxide electronic devices. These 2DEGs involve many-body interactions that give rise to a variety of physical phenomena such as superconductivity, magnetism, tunable metal–insulator transitions and phase separation. Increasing the mobility of the 2DEG, however, remains a major challenge. Here, we show that the electron mobility is enhanced by more than two orders of magnitude by inserting a single-unit-cell insulating layer of polar La1−xSrxMnO3 (x = 0, 1/8, and 1/3) at the interface between disordered LaAlO3 and crystalline SrTiO3 produced at room temperature. Resonant X-ray spectroscopy and transmission electron microscopy show that the manganite layer undergoes unambiguous electronic reconstruction, leading to modulation doping of such atomically engineered complex oxide heterointerfaces. At low temperatures, the modulation-doped 2DEG exhibits Shubnikov–de Haas oscillations and fingerprints of the quantum Hall effect, demonstrating unprecedented high mobility and low electron density