Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet.

OBJECTIVE: Food intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms. DESIGN: Jejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures. RESULTS: The most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline. CONCLUSION: Intestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.MRC [MRC_MC_UU_12012/3 MRC_MC_UU_12012/5] Wellcome Trust [106262/Z/14/Z, 106263/Z/14/Z, 100574/Z/12/Z]

The future of peer-to-peer trading of distributed renewable energy

The energy industry is transforming. Advances in energy generation and storage, digital technologies and platforms, robotics, Internet of Things, artificial intelligence and autonomous vehicles are driving tomorrow’s innovations, and enabling new business models to emerge. Unlike previous industrial revolutions, the digital revolution has no clear boundaries, and its development is likely to be ongoing, ubiquitous and rapid. In addition, accelerated adoption of new technologies and smart devices, especially among the tech-savvy digital natives, is increasingly empowering energy consumers of tomorrow to become ‘prosumers’ who generate as well as consume energy. The emergence of new peer-to-peer (P2P) business models across many industries, coupled with increasing interest by Australians in the sharing economy, could see the P2P business model extend to the energy industry of the future. Over the next decade, new P2P energy trading platforms may emerge to allow prosumers to trade their excess electricity with consumers who want to purchase affordable renewable energy. However, how will P2P energy trading be integrated into the existing energy system? Will P2P energy trading provide a secure, reliable and cost-effective mechanism for monetising DER? This report opens with the outcomes of a horizon scan of interconnected social, economic, geopolitical, technological and environmental trends driving transformation across the energy industry. Building on the analysed trends, the second part of the report presents future narratives describing how P2P energy trading may operate in 2030. With these insights, the government, energy and property industries, and consumers will be able to better navigate the uncertainties around P2P energy trading, and maximise the potential opportunities that this new energy system could bring over the next decade