Patchy Progress On Obesity Prevention: Emerging Exemplars, Entrenched Barriers, and New Thinking

Although there have been positive pockets of change, no country has yet turned around its obesity epidemic. Preventing an increase in obesity prevalence will require urgent actions from government as well as a broader spectrum of stakeholders than previously emphasized. In this paper, we review a number of regulatory and non-regulatory actions taken around the world to address obesity and discuss some of the reasons for the patchy progress. In addition, we preview the papers in this Lancet series, which each identify priority actions on key obesity issues and challenge some of the entrenched dichotomies that present obesity and its solutions in “either/or” terms. Although obesity is acknowledged as a complex issue, many debates about its causes and solutions are centered around overly simple dichotomies that present seemingly competing perspectives. Examples of such dichotomies explored in this series include: individual versus environmental causes of obesity, personal versus collective responsibilities for actions, supply versus demand explanations for consumption of unhealthy food, government regulation versus industry self-regulation, top down versus bottom up drivers for change, treatment versus prevention priorities, and under versus over nutrition focus. In the current paper, we explore the dichotomy of individual versus environmental drivers of obesity, which lay out two truths: people bear some personal responsibility for their health and environmental factors can readily support or undermine the ability of people to act in their self-interest. We propose a re-framing of obesity that emphasizes the reciprocal nature of the interaction between the environment and individual. Current food environments exploit people’s biological, psychological, social, and economic vulnerabilities, making it easier for them to eat unhealthful foods. This leads to preferences and demands for foods of poor nutritional quality, thus sustaining the unhealthful food environments. Breaking these vicious cycles will need regulatory actions from governments and greater efforts from industry and civil society

Mobilisation of Public Support for Policy Actions to Prevent Obesity

Public mobilisation is needed to enact obesity prevention policies and to mitigate backlash against their implementation. However, current approaches in public health focus primarily on dialogue between public health professionals and political leaders. Strategies to increase popular demand for obesity prevention policies include refining and streamlining public information, identifying effective frames for each population, enhancing media advocacy, building citizen protest and engagement, and developing a receptive political environment with change agents embedded across organisations and sectors. Long-term support and investment in collaboration among diverse stakeholders to create shared value is also important. Each actor in an expanded coalition for obesity prevention can make specific contributions to engaging, mobilising and coalescing the public. Shifting from a top-down to an integrated bottom-up and top-down approach would require an overhaul of current strategies and re-prioritisation of resources

How the structure of the large subunit controls function in an oxygen-tolerant [NiFe]-hydrogenase

Salmonella enterica is an opportunistic pathogen that produces a [NiFe]-hydrogenase under aerobic conditions. In the present study, genetic engineering approaches were used to facilitate isolation of this enzyme, termed Hyd-5. The crystal structure was determined to a resolution of 3.2 Å and the hydro-genase was observed to comprise associated large and small subunits. The structure indicated that His(229) from the large subunit was close to the proximal [4Fe–3S] cluster in the small subunit. In addition, His(229) was observed to lie close to a buried glutamic acid (Glu(73)), which is conserved in oxygen-tolerant hydrogenases. His(229) and Glu(73) of the Hyd-5 large subunit were found to be important in both hydrogen oxidation activity and the oxygen-tolerance mechanism. Substitution of His(229) or Glu(73) with alanine led to a loss in the ability of Hyd-5 to oxidize hydrogen in air. Furthermore, the H229A variant was found to have lost the overpotential requirement for activity that is always observed with oxygen-tolerant [NiFe]-hydrogenases. It is possible that His(229) has a role in stabilizing the super-oxidized form of the proximal cluster in the presence of oxygen, and it is proposed that Glu(73)could play a supporting role in fine-tuning the chemistry of His(229) to enable this function

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.SCOPUS: ar.jinfo:eu-repo/semantics/publishe