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Abstract Background Body composition and body fat distribution are important predictors of cardiometabolic diseases. The etiology of cardiometabolic diseases is heterogenous, and partly driven by inter-individual differences in tissue-specific insulin sensitivity. Objectives To investigate (1) the associations between body composition and whole-body, liver and muscle insulin sensitivity, and (2) changes in body composition and insulin sensitivity and their relationship after a 12-week isocaloric diet high in mono-unsaturated fatty acids (HMUFA) or a low-fat, high-protein, high-fiber (LFHP) diet. Methods This subcohort analysis of the PERSON study includes 93 individuals (53% women, BMI 25–40 kg/m2, 40–75 years) who participated in this randomized intervention study. At baseline and after 12 weeks of following the LFHP, or HMUFA diet, we performed a 7-point oral glucose tolerance test to assess whole-body, liver, and muscle insulin sensitivity, and whole-body magnetic resonance imaging to determine body composition and body fat distribution. Both diets are within the guidelines of healthy nutrition. Results At baseline, liver fat content was associated with worse liver insulin sensitivity (β [95%CI]; 0.12 [0.01; 0.22]). Only in women, thigh muscle fat content was inversely related to muscle insulin sensitivity (-0.27 [-0.48; -0.05]). Visceral adipose tissue (VAT) was inversely associated with whole-body, liver, and muscle insulin sensitivity. Both diets decreased VAT, abdominal subcutaneous adipose tissue (aSAT), and liver fat, but not whole-body and tissue-specific insulin sensitivity with no differences between diets. Waist circumference, however, decreased more following the LFHP diet as compared to the HMUFA diet (-3.0 vs. -0.5 cm, respectively). After the LFHP but not HMUFA diet, improvements in body composition were positively associated with improvements in whole-body and liver insulin sensitivity. Conclusions Liver and muscle insulin sensitivity are distinctly associated with liver and muscle fat accumulation. Although both LFHP and HMUFA diets improved in body fat, VAT, aSAT, and liver fat, only LFHP-induced improvements in body composition are associated with improved insulin sensitivity. Trial registration NCT03708419 (clinicaltrials.gov).

Abstract Continuous glucose monitoring (CGM) is a promising, minimally invasive alternative to plasma glucose measurements for calibrating physiology-based mathematical models of insulin-regulated glucose metabolism, reducing the reliance on in-clinic measurements. However, the use of CGM glucose, particularly in combination with insulin measurements, to develop personalized models of glucose regulation remains unexplored. Here, we simultaneously measured interstitial glucose concentrations using CGM as well as plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) in individuals with overweight or obesity to calibrate personalized models of glucose-insulin dynamics. We compared the use of interstitial glucose with plasma glucose in model calibration, and evaluated the effects on model fit, identifiability, and model parameters’ association with clinically relevant metabolic indicators. Models calibrated on both plasma and interstitial glucose resulted in good model fit, and the parameter estimates associated with metabolic indicators such as insulin sensitivity measures in both cases. Moreover, practical identifiability of model parameters was improved in models estimated on CGM glucose compared to plasma glucose. Together these results suggest that CGM glucose may be considered as a minimally invasive alternative to plasma glucose measurements in model calibration to quantify the dynamics of glucose regulation.

Abstract Background Tissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR. Methods This cross-sectional study included data from 214 women and men with BMI 25–40 kg/m2, aged 40–75 years, and with predominant muscle IR or liver IR. Tissue-specific IR was assessed using the muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI), which were calculated from the glucose and insulin responses during a 7-point oral glucose tolerance test. Plasma samples were collected before (T = 0) and after (T = 30, 60, 120, 240 min) consumption of a high-fat mixed meal and 247 metabolite measures, including lipoproteins, cholesterol, triacylglycerol (TAG), ketone bodies, and amino acids, were quantified using nuclear magnetic resonance spectroscopy. Differences in postprandial plasma metabolite iAUCs between muscle and liver IR were tested using ANCOVA with adjustment for age, sex, center, BMI, and waist-to-hip ratio. P-values were adjusted for a false discovery rate (FDR) of 0.05 using the Benjamini–Hochberg method. Results Sixty-eight postprandial metabolite iAUCs were significantly different between liver and muscle IR. Liver IR was characterized by greater plasma iAUCs of large VLDL (p = 0.004), very large VLDL (p = 0.002), and medium-sized LDL particles (p = 0.026), and by greater iAUCs of TAG in small VLDL (p = 0.025), large VLDL (p = 0.003), very large VLDL (p = 0.002), all LDL subclasses (all p

Accurate and robust estimation of individuals’ basal glucose level is a crucial measure in nutrition research but is typically estimated from one or more morning fasting samples. The use of Continuous Glucose Monitoring (CGM) devices presents an opportunity to define more robust basal glucose levels, which estimates can be generalized to any time of the day. However, to date, no standardized method has been delineated. The current paper seeks to define a reliable algorithm to characterize the individual’s basal glucose level over 24 h from CGM measurements. Data drawn from four nutritional intervention studies performed on adults free from chronic diseases were used to define that basal glucose levels were optimally estimated using the 40th percentile of the previous 24 h CGM data. This simple algorithm provides a Continuous Glucose Baseline over 24 h (24 h-CGB) that is an unbiased and highly correlated estimator (r = 0.86, p-value

Abstract Free‐ranging domestic cats Felis catus, from owned pets to feral cats, impact biodiversity through predation, fear effects, competition, disease and hybridization. Scientific knowledge regarding these impacts has recently increased, making it timely to assess the role of nature conservation legislation in this connection. We do so with particular regard to the obligations of governments around the world under international wildlife law. First, we provide an overview of current knowledge, based on a literature review, concerning the ways in which domestic cats impact wildlife; the resulting effects on native species’ populations and ecosystems; and available strategies for addressing these issues. In light of this knowledge, using standard legal research methodology, we then identify and interpret relevant legal instruments, with a particular focus on international wildlife treaties. Lastly, we identify and assess factors that may influence the implementation of relevant obligations. The outcomes of this analysis indicate that numerous legal obligations of relevance to free‐ranging domestic cats already apply under global treaties such as the Convention on Biological Diversity, Convention on Migratory Species and World Heritage Convention, and a range of regional legal instruments for biodiversity conservation. Of particular significance are obligations concerning (a) invasive alien species; (b) protected areas and (c) protected species. Many national authorities around the world are currently required, under international law, to adopt and implement policies aimed at preventing, reducing or eliminating the biodiversity impacts of free‐ranging domestic cats, in particular by (a) removing feral and other unowned cats from the landscape to the greatest extent possible and (b) restricting the outdoor access of owned cats. Factors that can influence or impair the application of these obligations include considerations of feasibility, scientific uncertainty, the interests of cat owners and the (perceived) interests of domestic cats themselves. Even if such factors may to some extent explain why many authorities have hitherto failed to take effective action to address the threats posed by free‐ranging domestic cats, from a legal perspective these factors provide little ground for justifying non‐compliance with international wildlife law. A free Plain Language Summary can be found within the Supporting Information of this article.

Obesity is associated with chronic inflammation and metabolic complications, including insulin resistance (IR). Immune cells drive inflammation through the rewiring of intracellular metabolism. However, the impact of obesity-related IR on the metabolism and functionality of circulating immune cells, like monocytes, remains poorly understood. To increase insight into the interindividual variation of immunometabolic signatures among individuals and their role in the development of IR, we assessed systemic and tissue-specific IR and circulating immune markers, and we characterized metabolic signatures and cytokine secretion of circulating monocytes from 194 individuals with a BMI ≥25 kg/m2. Monocyte metabolic signatures were defined using extracellular acidification rates (ECARs) to estimate glycolysis and oxygen consumption rates (OCRs) for oxidative metabolism. Although monocyte metabolic signatures and function based on cytokine secretion varied greatly among study participants, they were strongly associated with each other. The ECAR-to-OCR ratio, representing the balance between glycolysis and oxidative metabolism, was negatively associated with fasting insulin levels, systemic IR, and liver-specific IR. These results indicate that monocytes from individuals with IR were relatively more dependent on oxidative metabolism, whereas monocytes from more insulin-sensitive individuals were more dependent on glycolysis. Additionally, circulating CXCL11 was negatively associated with the degree of systemic IR and positively with the ECAR-to-OCR ratio in monocytes, suggesting that individuals with high IR and a monocyte metabolic dependence on oxidative metabolism also have lower levels of circulating CXCL11. Our findings suggest that monocyte metabolism is related to obesity-associated IR progression and deepen insights into the interplay between innate immune cell metabolism and IR development in humans. Article Highlights: This study explored associations between monocyte metabolic and functional responses with the degree of systemic and tissue-specific insulin resistance (IR) in 185 healthy individuals with overweight and obesity. Monocyte metabolic and functional responses exhibited high interindividual variation but were positively associated. The monocyte metabolic dependency was associated with the degree of systemic IR. Monocytes from insulin-resistant individuals used relatively more oxidative metabolism than those from insulin-sensitive individuals. Circulating inflammatory mediators, including CXCL11, were associated with systemic IR and monocyte metabolism and could be involved in the mechanisms behind the effects of overweight and obesity and IR on monocyte metabolism. [ABSTRACT FROM AUTHOR]

Background: It is well-established that the etiology of type 2 diabetes differs between individuals. Insulin resistance (IR) may develop in different tissues, but the severity of IR may differ in key metabolic organs such as the liver and skeletal muscle. Recent evidence suggests that these distinct tissue-specific IR phenotypes may also respond differentially to dietary macronutrient composition with respect to improvements in glucose metabolism.Objective: The main objective of the PERSON study is to investigate the effects of an optimal vs. suboptimal dietary macronutrient intervention according to tissue-specific IR phenotype on glucose metabolism and other health outcomes.Methods: In total, 240 overweight/obese (BMI 25 – 40 kg/m2) men and women (age 40 – 75 years) with either skeletal muscle insulin resistance (MIR) or liver insulin resistance (LIR) will participate in a two-center, randomized, double-blind, parallel, 12-week dietary intervention study. At screening, participants undergo a 7-point oral glucose tolerance test (OGTT) to determine the hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), classifying each participant as either “No MIR/LIR,” “MIR,” “LIR,” or “combined MIR/LIR.” Individuals with MIR or LIR are randomized to follow one of two isocaloric diets varying in macronutrient content and quality, that is hypothesized to be either an optimal or suboptimal diet, depending on their tissue-specific IR phenotype (MIR/LIR). Extensive measurements in a controlled laboratory setting as well as phenotyping in daily life are performed before and after the intervention. The primary study outcome is the difference in change in disposition index, which is the product of insulin sensitivity and first-phase insulin secretion, between participants who received their hypothesized optimal or suboptimal diet.Discussion: The PERSON study is one of the first randomized clinical trials in the field of precision nutrition to test effects of a more personalized dietary intervention based on IR phenotype. The results of the PERSON study will contribute knowledge on the effectiveness of targeted nutritional strategies to the emerging field of precision nutrition, and improve our understanding of the complex pathophysiology of whole body and tissue-specific IR.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03708419, clinicaltrials.gov as NCT03708419.

Abstract The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co‐morbidity, and premature death. An important cause of physical limitations is the age‐related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation–contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing.

The lion (Panthera leo) is featuring ever more prominently on the agendas of international wildlife treaties like the Convention on International Trade in Endangered Species (CITES) and the Convention on the Conservation of Migratory Species of Wild Animals (CMS). Lion range and numbers have declined markedly over the last two decades. In this review we assess the present role of international wildlife treaties with a view to improving their combined contribution to the conservation and sustainable use of lions. Our analysis identifies a substantial body of relevant international wildlife law and, moreover, a significant potential for enhancing the contribution to lion conservation of these global and regional treaties. The time is right to invest in such improvements, and our review renders a range of general and treaty-specific recommendations for doing so, including making full use of the Ramsar Wetlands Convention, World Heritage Convention and transboundary conservation area (TFCA) treaties for lion conservation. The CMS holds particular potential in this regard and our analysis provides strong support for listing the lion in its Appendices.

As wolf populations expand across Europe, many countries face challenges in finding ways to address the concerns of some elements among the rural stakeholders who are being asked to share their landscapes with wolves for the first time in several generations. In these recovery landscapes, wolves are associated with a wide range of conflicts that include economic, psychological, perceptional, social, cultural and political dimensions. A recurring demand concerns the desire to introduce the use of carefully regulated lethal control of wolves, through either culling by state employees or hunting conducted by rural hunters. Introducing such measures can be very controversial, and many critics challenge their legality under the international wildlife conservation instruments that have nurtured wolf recovery. We evaluate this issue for the case of wolves in Norway, which are strictly protected under the Bern Convention. Drawing on the latest results of social science research, we present the multiple lines of argumentation that are often used to justify killing wolves and relate these to the criteria for exceptions that exist under the Bern Convention. We conclude that while the Convention provides apparent scope for allowing the killing of wolves as a means to address conflicts, this must be clearly justified and proportional to the conservation status of wolves so as to not endanger their recovery.

The relevance of the Convention on Migratory Species (CMS) for large carnivores is on the increase. Its appendices currently feature polar bear, Gobi bear, African wild dog, lion, leopard, snow leopard, and cheetah. This increased involvement raises various issues and debates concerning, inter alia, the value added by the CMS as compared to other treaties; the scope of the CMS in relation to its definition of “migratory species”; and the Convention's implications for the sustainable use of listed large carnivores. We present these and similar emerging questions within their broader context, provide beginnings of answers, and outline an agenda for further research. We further highlight the need for improved interpretive guidance on aspects of the Convention's legal text and its implications for sustainable use.

Cardiometabolic diseases are one of the leading causes for disability and mortality in the Western world. The prevalence of these chronic diseases is expected to rise even further in the next decades. Insulin resistance (IR) and related metabolic disturbances are linked to ectopic fat deposition, which is the storage of excess lipids in metabolic organs such as liver and muscle. Notably, a vicious circle exists between IR and ectopic fat, together increasing the risk for the development of cardiometabolic diseases. Nutrition is a key-determining factor for both IR and ectopic fat deposition. The macronutrient composition of the diet may impact metabolic processes related to ectopic fat accumulation and IR. Interestingly, however, the metabolic phenotype of an individual may determine the response to a certain diet. Therefore, population-based nutritional interventions may not always lead to the most optimal (cardiometabolic) outcomes at the individual level, and differences in the metabolic phenotype may underlie conflicting findings related to IR and ectopic fat in dietary intervention studies. Detailed metabolic phenotyping will help to better understand the complex relationship between diet and metabolic regulation, and to optimize intervention outcomes. A subgroup-based approach that integrates, among others, tissue-specific IR, cardiometabolic parameters, anthropometrics, gut microbiota, age, sex, ethnicity, and psychological factors may thereby increase the efficacy of dietary interventions. Nevertheless, the implementation of more personalized nutrition may be complex, costly, and time consuming. Future studies are urgently warranted to obtain insight into a more personalized approach to nutritional interventions, taking into account the metabolic phenotype to ultimately improve insulin sensitivity and reduce the risk for cardiometabolic diseases.

In 2008, South Africa adopted its ‘National Norms and Standards for the Management of Elephants in South Africa’. Concern has subsequently been raised as to whether these norms and standards apply to free-ranging elephant on land, which had not been enclosed with a fence with the express purpose of containing these animals and other game on the property. The application of these norms and standards pivots on whether the owner(s) of the property have taken possession of these animals in accordance with common law applicable to game, or have given effect to the provisions of the Game Theft Act. To address this concern, this article briefly explores the evolution of South African regulatory jurisprudence applicable to game, including elephant, and analyses the norms and standards in relation to international and national legislation and common law applying to elephants. The norms and standards are not applicable to unowned, free-roaming elephant. These norms and standards, therefore, do not fulfil their primary objective of uniform management of elephant across South Africa. This limitation of the norms and standards, therefore, needs to be considered when they are revised.

The Habitats Directive requires EU member states to prohibit the "deliberate disturbance" of mammals, reptiles, amphibians, fish and invertebrates belonging to species listed in its Annex IV. Through analysis of legislation, case law, guidance documents and practical examples, this article explores the question what types of activities, under what conditions, constitute such deliberate disturbance. The analysis shows that, even if some question marks concerning the disturbance prohibition's scope remain, many of the prohibition's implications have by now been clarified by the EU Court of Justice. These implications appear to be of considerable practical importance. [ABSTRACT FROM AUTHOR]

Objective: A proinflammatory adipose tissue (AT) microenvironment and systemic low‐grade inflammation may differentially affect tissue‐specific insulin sensitivity. This study investigated the relationships of abdominal subcutaneous AT (aSAT) and circulating immune cells, aSAT gene expression, and circulating inflammatory markers with liver and skeletal muscle insulin sensitivity in people with overweight and obesity. Methods: Individuals with overweight and obesity from the PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study (n = 219) and the Maastricht Study (replication cohort; n = 1256) underwent a seven‐point oral glucose tolerance test to assess liver and muscle insulin sensitivity, and circulating inflammatory markers were determined. In subgroups, flow cytometry was performed to identify circulating and aSAT immune cells, and aSAT gene expression was evaluated. Results: The relative abundances of circulating T cells, nonclassical monocytes, and CD56dim CD16+ natural killer cells were inversely associated with liver, but not muscle, insulin sensitivity in the PERSON Study. The inverse association between circulating (classical) monocytes and liver insulin sensitivity was confirmed in the Maastricht Study. In aSAT, immune cell populations were not related to insulin sensitivity. Furthermore, aSAT gene expression of interleukin 6 and CD14 was positively associated with muscle, but not liver, insulin sensitivity. Conclusions: The present findings demonstrate that circulating immune cell populations and inflammatory gene expression in aSAT show distinct associations with liver and muscle insulin sensitivity. [ABSTRACT FROM AUTHOR]

The ongoing refugee crisis in Europe has seen many countries rush to construct border security fencing to divert or control the flow of people. This follows a trend of border fence construction across Eurasia during the post-9/11 era. This development has gone largely unnoticed by conservation biologists during an era in which, ironically, transboundary cooperation has emerged as a conservation paradigm. These fences represent a major threat to wildlife because they can cause mortality, obstruct access to seasonally important resources, and reduce effective population size. We summarise the extent of the issue and propose concrete mitigation measures.

Species migrating across boundaries represent the classic case for international cooperation in biodiversity conservation. Climate change is adding fresh challenges to such cooperation, on account of the shifting ranges and particular vulnerabilities to climate change of migratory wildlife. In view of the need to help migratory species adapt to climate change with minimal losses, this article performs an in-depth analysis of the present and potential future role in respect of climate adaptation of the main intergovernmental regime for migratory species conservation, the 1979 Bonn Convention on the Conservation of Migratory Species of Wild Animals (CMS) and its various daughter instruments.

The contamination of the world's oceans by human garbage, especially plastics, ranks among those environmental problems whose resolution appears remote, despite the considerable public attention paid to the 'Great Garbage Patch' in the Pacific, 'plastic soup', and the like. This 'marine litter' (or 'marine debris') problem is characterized by diffuse sources and an array of adverse environmental impacts, including entanglement of and ingestion by albatrosses, fulmars, turtles, seals and a variety of other marine wildlife. This article explores the evolving role of international law in the efforts to manage marine litter, including recent developments involving the Convention for the Protection of the Marine Environment of the North-East Atlantic (OSPAR Convention) and the European Union's Marine Strategy Framework Directive (MSFD).