Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of beta-adrenergic G protein-coupled... Show moreThermogenic 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. Show less
McLaren, S.; Berardy, A.; Henderson, A.; Holden, N.; Huppertz, T.; Jolliet, O.; ... ; Zanten, H. van 2021
This report is the outcome of a consensus-building project to agree on best practices for environmental and nutritional Life Cycle Assessment (nLCA) methodology, and identify future research needs.... Show moreThis report is the outcome of a consensus-building project to agree on best practices for environmental and nutritional Life Cycle Assessment (nLCA) methodology, and identify future research needs. The project involved 30 nutritional and environmental LCA researchers from 18 countries. It focused on the assessment of food items (as opposed to meals or diets).Best practice recommendations were developed to address the intended purpose of an LCA study and related modeling approach, choice of an appropriate functional unit, assessment of nutritional value, and reporting nLCA results. An nLCA study should report the quantities of as many essential nutrients as possible and aim to provide information on the nutritional quality and/or health impacts in addition to nutrient quantities. Outstanding issues requiring further research attention include: defining a minimum number of nutrients to be considered in an nLCA study; treatment of nutrients to limit; use of nutrient indexes; further development of Impact Assessment methods; representation of nutritional changes that may occur during subsequent distribution and food preparation in cradle-to-gate nLCA studies; and communication of data uncertainty and variability. More data are required for different regions (particularly developing countries); for the processing, distribution, retail, and consumption life cycle stages; and for food loss and waste. Finally, there is a need to extend nLCA methodology for the assessment of meals and diets, to consider further how to account for the multi-functionality of food in a sustainability framework, and to set nLCA studies within the context of environmental limits.These results provide a robust basis for improving nLCA methodology and applying it to identify solutions that minimize the trade-offs between nourishing populations and safeguarding the environment. Show less
Nogueras-Lara, F.; Gallego-Calvente, A.T.; Dong, H.; Gallego-Cano, E.; Girard, J.H.V.; Hilker, M.; ... ; Schödel, R. 2018
