Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids - A Double Blind, Randomised Clinical Trial.

Background: Obesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation. Methods: To evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration. Results: Obesity was associated with scWAT hypertrophy (P < 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration (P = 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways (P <0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals. Conclusion: Our data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN96712688.

Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial.

BACKGROUND: Obesity is associated with enhanced inflammation. However, investigation in human subcutaneous white adipose tissue (scWAT) is limited and the mechanisms by which inflammation occurs have not been well elucidated. Marine long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and may reduce scWAT inflammation. METHODS: Subcutaneous white adipose tissue (scWAT) biopsies were collected from individuals living with obesity (n=45) and normal weight individuals (n=39) prior to and following a 12-week intervention with either 3 g/day of a fish oil concentrate (providing 1.1 g eicosapentaenoic acid (EPA) + 0.8 g docosahexaenoic acid (DHA)) or 3 g/day of corn oil. ScWAT fatty acid, oxylipin, and transcriptome profiles were assessed by gas chromatography, ultra-pure liquid chromatography tandem mass spectrometry, RNA sequencing and qRT-PCR, respectively. FINDINGS: Obesity was associated with greater scWAT inflammation demonstrated by lower concentrations of specialised pro-resolving mediators (SPMs) and hydroxy-DHA metabolites and an altered transcriptome with differential expression of genes involved in LC n-3 PUFA activation, oxylipin synthesis, inflammation, and immune response. Intervention with LC n-3 PUFAs increased their respective metabolites including the SPM precursor 14-hydroxy-DHA in normal weight individuals and decreased arachidonic acid derived metabolites and expression of genes involved in immune and inflammatory response with a greater effect in normal weight individuals. INTERPRETATION: Downregulated expression of genes responsible for fatty acid activation and metabolism may contribute to an inflammatory oxylipin profile and limit the effects of LC n-3 PUFAs in obesity. There may be a need for personalised LC n-3 PUFA supplementation based on obesity status. FUNDING: European Commission Seventh Framework Programme (Grant Number 244995) and Czech Academy of Sciences (Lumina quaeruntur LQ200111901).

Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids.

Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5-25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30-40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.

Material flow analysis of scarce metals: sources, functions, end-uses and aspects for future supply.

A number of metals that are now important to the electronic industry (and others) will become much more important in the future if current trends in technology continue. Most of these metals are byproducts (or hitch-hikers) of a small number of important industrial metals (attractors). By definition, the metals in the hitch-hiker group are not mined by themselves, and thus their production is limited by the demand for the major attractors. This article presents a material flow analysis (MFA) of the complex inter-relationships between these groups of metals. First, it surveys the main sources of geologically scarce (byproduct) metals currently considered critical by one or other of several recent studies. This is followed by a detailed survey of their major functions and the quantities contained in intermediate and end-products. The purpose is to identify the sectors and products where those metals are used and stocked and thus potentially available for future recycling. It concludes with a discussion of the limitations of possible substitution and barriers to recycling.

Material efficiency: rare and critical metals.

In the last few decades, progress in electronics, especially, has resulted in important new uses for a number of geologically rare metals, some of which were mere curiosities in the past. Most of them are not mined for their own sake (gold, the platinum group metals and the rare Earth elements are exceptions) but are found mainly in the ores of the major industrial metals, such as aluminium, copper, zinc and nickel. We call these major metals 'attractors' and the rare accompanying metals 'hitch-hikers'. The key implication is that rising prices do not necessarily call forth greater output because that would normally require greater output of the attractor metal. We trace the geological relationships and the functional uses of these metals. Some of these metals appear to be irreplaceable in the sense that there are no known substitutes for them in their current functional uses. Recycling is going to be increasingly important, notwithstanding a number of barriers.

Exergy efficiency in industry: where do we stand?

Efficiency is a term generally used to determine how well a system performs. However, efficiency can have different meanings and, unaccompanied by a formal definition or taken out of context, can lead to serious misconceptions. In many official publications, efficiency is calculated as the ratio of useful output to energy input. This measure reflects the first law of thermodynamics (conservation of energy) but does not reflect the potential for improvement. A better measure, that also reflects the second law of thermodynamics, is the ratio of the potential useful (exergy) output to the potential useful (exergy) input. We estimate second law efficiencies for the inorganic and organic chemical industries to be 29% and 35% respectively. We also estimate the efficiency of the U.S. industry sector as a whole to be 37.6%, as compared to only 7.7% for the overall U.S. economy. These figures are far lower than the "first law" figures published by the U.S. Department of Energy (80% for industry and 42.5% overall) and they imply a significant potential for improvement.

A model and treatment for autism at the convergence of Chinese medicine and Western science: first 130 cases.

OBJECTIVE: To present a model for autism showing that impairment of sensory and self-regulation is the core deficit that underlies delays in social/language skills and abnormal behavior in autism; and to demonstrate the efficacy of a treatment for autism based on Chinese medicine. METHODS: Children with autism under 6 years of age were assigned to treatment or wait-list conditions. A total of 130 children were treated and the results compared with 45 wait-list controls. Treatment is a tuina methodology directed at sensory impairment--Kai Qiao Tuina. The treatment was a five-month protocol that was implemented daily by trained parents via trained support staff. The effects of treatment on the main symptoms, autistic behavior, social/language delay, sensory and self-regulatory impairment, as well as on parenting stress, were observed and compared. RESULTS: The treatment had a large effect size (P<0.0001) on measures of sensory and self-regulation. The evaluations done by pre-school teachers demonstrated improvement in the measures of autism (P<0.003), and were confirmed by evaluations done by parents (P<0.0001). There was a large decrease (P<0.0001) in parenting stress. CONCLUSIONS: Sensory and self-regulatory impairment is a main factor in the development and severity of autism. Treatment of young children with autism with Kai Qiao Tuina resulted in a decrease in sensory and self-regulatory impairment and a reduction in severity of measures of autism.

Qigong massage treatment for sensory and self-regulation problems in young children with autism: a randomized controlled trial.

Autism is commonly associated with sensory and self-regulatory disturbances. This article presents a randomized controlled study evaluating the effect of a 5-month intervention directed toward improving sensory impairment, digestion, and sleep in 46 children with autism < age 6. The intervention, Qigong Sensory Training (QST), is a qigong massage intervention based in Chinese medicine. It is two-pronged: Trainers work with children directly 20 times over 5 months, and parents give the massage daily to their children. Improvement was evaluated in two settings--preschool and home--by teachers (blind to group) and parents. Teacher evaluations showed that treated children had significant classroom improvement of social and language skills and reduction in autistic behavior compared with wait-list control participants. These findings were confirmed by parent data, indicating that the gains had generalized across contexts. A model and supporting data for understanding and treating sensory and self-regulation problems in autism is presented.

Outcomes of a pilot training program in a qigong massage intervention for young children with autism.

Sensory impairment is a common and significant feature of children on the autism spectrum. In 2005, a qigong massage intervention based on Chinese medicine and delivered by a doctor of Chinese medicine was shown to improve sensory impairment and adaptive behavior in a small controlled study of young children with autism. In 2006, the Qigong Sensory Training (QST) program was developed to train early intervention professionals to provide the QST intervention. This article describes the preliminary evaluation of the QST program as piloted with 15 professionals and 26 children and outcomes testing using standardized tests of sensory impairment and adaptive behavior. Results of outcomes comparing delivery by QST-trained therapists with delivery by a doctor of Chinese medicine showed that both groups improved and that there was no difference in outcome between the two groups. The intervention and training program are described, and implications for future research are discussed.

Efficiency dilution: long-term exergy conversion trends in Japan.

This analysis characterizes century-scale trends in exergy efficiency in Japan. Exergy efficiency captures the degree to which energy inputs (such as coal) are converted into useful work (such as electricity or power to move a vehicle). This approach enables the estimation of net efficiencies which aggregate different technologies. Sectors specifically analyzed are electricity generation, transport, steel production, and residential space heating. One result is that the aggregate exergy efficiency of the Japanese economy declined slightly over the last half of the 20th century, reaching a high of around 38% in the late 1970s and falling to around 33% by 1998. The explanation for this is that while individual technologies improved dramatically over the century, less exergy-efficient ones were progressively adopted, yielding a net stabilization or decline. In the electricity sector, for instance, adoption of hydropower was followed by fossil-fired plants and then by nuclear power, each technology being successively less efficient from an exergy perspective. The underlying dynamic of this trend is analogous to declining ore grades in the mining sector. Increasing demand for exergy services requires expended utilization of resources from which it is more difficult to extract utility (e.g., falling water versus coal). We term this phenomenon efficiency dilution.

The 1.7 kilogram microchip: energy and material use in the production of semiconductor devices.

The scale of environmental impacts associated with the manufacture of microchips is characterized through analysis of material and energy inputs into processes in the production chain. The total weight of secondary fossil fuel and chemical inputs to produce and use a single 2-gram 32MB DRAM chip are estimated at 1600 g and 72 g, respectively. Use of water and elemental gases (mainly N2) in the fabrication stage are 32,000 and 700 g per chip, respectively. The production chain yielding silicon wafers from quartz uses 160 times the energy required for typical silicon, indicating that purification to semiconductor grade materials is energy intensive. Due to its extremely low-entropy, organized structure, the materials intensity of a microchip is orders of magnitude higher than that of "traditional" goods. Future analysis of semiconductor and other low entropy high-tech goods needs to include the use of secondary materials, especially for purification.