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Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis1. 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 α1-adrenergic receptor (AR) and β3-AR signalling induces the expression of thermogenic genes of the futile creatine cycle2,3, and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo. NA triggers physical and functional coupling between the α1-AR subtype (ADRA1A) and Gαq to promote adipocyte thermogenesis in a manner that is dependent on the effector proteins of the futile creatine cycle, creatine kinase B and tissue-non-specific alkaline phosphatase. Combined Gαq and Gαs signalling selectively in adipocytes promotes a continual rise in whole-body energy expenditure, and creatine kinase B is required for this effect. Thus, the ADRA1A-Gαq-futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis.

Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and cardiovascular disease1. Thermogenesis by adipocytes can counteract obesity and metabolic diseases2,3. In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP-purportedly via a phosphorylation cycle4-to drive thermogenic respiration. However, the proteins that control this futile creatine cycle are unknown. Here we show that creatine kinase B (CKB) is indispensable for thermogenesis resulting from the futile creatine cycle, during which it traffics to mitochondria using an internal mitochondrial targeting sequence. CKB is powerfully induced by thermogenic stimuli in both mouse and human adipocytes. Adipocyte-selective inactivation of Ckb in mice diminishes thermogenic capacity, increases predisposition to obesity, and disrupts glucose homeostasis. CKB is therefore a key effector of the futile creatine cycle.

In eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones and redox proteins including SCO1, SCO2, and COA6, a recently discovered protein whose molecular function is unknown. To uncover the molecular mechanism by which COA6 and SCO proteins mediate copper delivery to COX2, we have solved the solution structure of COA6, which reveals a coiled-coil-helix-coiled-coil-helix domain typical of redox-active proteins found in the mitochondrial inter-membrane space. Accordingly, we demonstrate that COA6 can reduce the copper-coordinating disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. Finally, our determination of the interaction surfaces and reduction potentials of COA6 and its client proteins provides a mechanism of how metallochaperone and disulfide reductase activities are coordinated to deliver copper to CcO.

Aim Method Results Conclusion To qualitatively explore the experiences of individuals with Gestational Diabetes Mellitus (GDM) in Australia, and to recognise opportunities for leveraging digital health to enhance the support of GDM management.A cross sectional online survey assessed the experiences of individuals with GDM, the healthcare system and their digital health usage. Respondents (recruited via a national diabetes registry or social media) were adults receiving GDM care within Australia in the last 5 years, who responded to any of three open‐ended questions (n = 815) exploring positive, negative and other GDM experiences. Thematic analysis was utilised, and themes were mapped to the socio‐ecological systems framework.At a system level, themes related to (1) accessibility of care including the value of digital health and the inflexible or inconsistent perception of the (2) implementation of guidelines. At an interpersonal level, themes covered the need for adequate (3) health information provision, and (4) supportive care, as well as highlighting (5) experiences of stigma including a desire for greater awareness of GDM. Individual‐level themes included: (6) differential barriers to accessing care; (7) negative emotional burden; (8) internalisation of stigma; (9) dietary freedom and social impact and (10) opportunity for change derived from having GDM.Findings suggest a demand for more supportive, person‐centred GDM care, improved information provision and individualised implementation of clinical guidelines. Such mechanisms may support reduced barriers to accessing care or negative psychosocial impacts of GDM. Though not central to the identified experiences, digital health tools may help address the need for optimised GDM care. [ABSTRACT FROM AUTHOR]

Aim: In Australian adults, this study seeks to describe the experiences and factors associated with the perceived outcomes of using a very low calorie diet (VLCD) program for ≥4 weeks. Methods: A mixed method study using the method perspective was conducted to analyse individual semi‐structured interviews conducted via videoconference and cross‐sectional survey data. Australians 18 to 65 years were eligible if they were currently consuming at least one VLCD product daily for ≥4 weeks or had ceased consumption within 4 weeks. Interviews were thematically analysed. Results: Weight loss (19 kg [SD: 18 kg]) and duration (5 months [SD: 5 months]) of VLCD product use of the 31 participants (female: 97%, 44 [SD: 11] years, body mass index >30 kg/m2: 84%) were strongly correlated (r = 0.73, P <.001). Participants' experiences were influenced by a journey of learning from their previous weight loss attempts, discerned the VLCD program as credible, and chose to commence the VLCD due to a convergence of internal motivators. Early health‐related outcomes were a reinforcing stimulus and participants developed new health behaviours but felt dependent on the VLCD long term. Throughout these experiences the participants identified various individual, program structure, and environment related factors which either facilitated their VLCD program use or created barriers to achieving their goals. Health care professionals were minimally engaged. Conclusions: A model of care to support facilitators and overcome barriers would mean more meaningful engagement of health care professionals to ultimately improve the experience and adherence of the VLCD program users in Australia. [ABSTRACT FROM AUTHOR]

Australia and New Zealand are currently reviewing the regulations governing nutrition function, health and related claims on foods. Health claims currently are not permitted on food labels, with one exception. The aim of this study was to describe the use of such claims on packaged food for sale in Australia (excluding nutrient content claims) prior to any changes to the regulations, and measure compliance with existing regulations. A survey was conducted of the labelling of 7850 products (including multiple pack sizes of individual foods) in 47 different food categories on sale in New South Wales in 2003. A total of 2098 nutrition function, health or related claims and 12 therapeutic claims were recorded. Fourteen percent of products carried some sort of claim. If nutrient function and general health maintenance claims are excluded, 8.1% of products carried a health or related claim. Using the claims categorisation proposed by Food Standards Australia New Zealand for a new standard on claims, general-level claims were found on 9.8% of products and high-level and therapeutic claims (illegal at the time) on 1.2%. The food categories with the highest proportion of products carrying claims were sports drinks (92%), energy drinks (84%), sports bars (57%) and breakfast cereals (54%). 118 high-level and therapeutic claims did not conform to current food standards and there were many general-level claims for ingredient benefits that were unlikely to be able to be scientifically substantiated. The results of this survey suggest that more than 5% of claims were not complying with the current regulations and that the standards were not being fully enforced. To be effective, the new standard will need to be accompanied by clear guidelines for manufacturers on requirements for substantiating claims. Comprehensive education and enforcement frameworks also will be needed, to reduce the number of illegal or apparently unsubstantiated claims. [ABSTRACT FROM AUTHOR]

Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis 1 . 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 1 -adrenergic receptor (AR) and β 3 -AR signalling induces the expression of thermogenic genes of the futile creatine cycle 2,3 , and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo. NA triggers physical and functional coupling between the α 1 -AR subtype (ADRA1A) and Gα q to promote adipocyte thermogenesis in a manner that is dependent on the effector proteins of the futile creatine cycle, creatine kinase B and tissue-non-specific alkaline phosphatase. Combined Gα q and Gα s signalling selectively in adipocytes promotes a continual rise in whole-body energy expenditure, and creatine kinase B is required for this effect. Thus, the ADRA1A-Gα q -futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis., (© 2022. The Author(s).)