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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]

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]

Aim: The aim of this study is to investigate associations between the physical activity (PA) spectrum (sedentary behavior to exercise) and tissue‐specific insulin resistance (IR). Methods: We included 219 participants for analysis (median [IQR]: 61 [55; 67] years, BMI 29.6 [26.9; 32.0] kg/m2; 60% female) with predominant muscle or liver IR, as determined using a 7‐point oral glucose tolerance test (OGTT). PA and sedentary behavior were measured objectively (ActivPAL) across 7 days. Context‐specific PA was assessed with the Baecke questionnaire. Multiple linear regression models (adjustments include age, sex, BMI, site, season, retirement, and dietary intake) were used to determine associations between the PA spectrum and hepatic insulin resistance index (HIRI), muscle insulin sensitivity index (MISI) and whole‐body IR (HOMA‐IR, Matsuda index). Results: In fully adjusted models, objectively measured total PA (standardized regression coefficient β = 0.17, p = 0.020), light‐intensity PA (β = 0.15, p = 0.045) and moderate‐to‐vigorous intensity PA (β = 0.13, p = 0.048) were independently associated with Matsuda index, but not HOMA‐IR (p > 0.05). A higher questionnaire‐derived sport index and leisure index were associated with significantly lower whole‐body IR (Matsuda, HOMA‐IR) in men but not in women. Results varied across tissues: more time spent sedentary (β = −0.24, p = 0.045) and a higher leisure index (β = 0.14, p = 0.034) were respectively negatively and positively associated with MISI, but not HIRI. A higher sport index was associated with lower HIRI (β = −0.30, p = 0.007, in men only). Conclusion: While we confirm a beneficial association between PA and whole‐body IR, our findings indicate that associations between the PA spectrum and IR seem distinct depending on the primary site of insulin resistance (muscle or liver). [ABSTRACT FROM AUTHOR]

Digital twins provide a new paradigm for the integrated use of sensor data, process-based and data-driven modelling, and user interaction, to explore the behaviour of individual objects and processes. Digital twins originate from an engineering context and were developed for machines and mainly physical and chemical processes. In this paper, we further develop an understanding of digital twins for the green life sciences, which also include biological and social processes. We report on three use cases, in precision farming, greenhouse control and personalized dietary advice, focusing on practical benefits and challenges of digital twins compared with other research methods. This research extends earlier more conceptual research on digital twins in this domain. We find benefits in increased accuracy and impact because of the real-time data connection of digital twins to their real-life counterparts. Specification, availability and accuracy of relevant data sources are still major challenges. Specifically, when using digital twins for personalized advice, further research is needed on nontechnical aspects so that users will comply with the advice from the digital twins. We have outlined four directions of future research and expect that further research will include data-driven modelling to simulate the complex character of living objects and processes and at the same time develop approaches to limit the amount of required input data. [ABSTRACT FROM AUTHOR]

Recent studies suggest that circulating fibroblast growth factor 21 (FGF21) may be a marker of metabolic health status. We performed a secondary analysis of a 12-week randomized controlled trial to investigate the effects of two energy restriction (ER) diets on fasting and postprandial plasma FGF21 levels, as well as to explore correlations of plasma FGF21 with metabolic health markers, (macro)nutrient intake and sweet-taste preference. Abdominally obese subjects aged 40–70 years (n = 110) were randomized to one of two 25% ER diets (high-nutrient-quality diet or low-nutrient-quality diet) or a control group. Plasma FGF21 was measured in the fasting state and 120 min after a mixed meal. Both ER diets did not affect fasting or postprandial plasma FGF21 levels despite weight loss and accompanying health improvements. At baseline, the postprandial FGF21 response was inversely correlated to fasting plasma glucose (ρ = −0.24, p = 0.020) and insulin (ρ = −0.32, p = 0.001), HOMA-IR (ρ = −0.34, p = 0.001), visceral adipose tissue (ρ = −0.24, p = 0.046), and the liver enzyme aspartate aminotransferase (ρ = −0.23, p = 0.021). Diet-induced changes in these markers did not correlate to changes in plasma FGF21 levels upon intervention. Baseline higher habitual polysaccharide intake, but not mono- and disaccharide intake or sweet-taste preference, was related to lower fasting plasma FGF21 (p = 0.022). In conclusion, we found no clear evidence that fasting plasma FGF21 is a marker for metabolic health status. Circulating FGF21 dynamics in response to an acute nutritional challenge may reflect metabolic health status better than fasting levels. [ABSTRACT FROM AUTHOR]

Background Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. Objectives The aim of the study was to examine the additional effects of nutrient quality on top of ER. Methods A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov : NCT02194504). Participants aged 40–70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n  = 40); a 25% ER low-nutrient-quality diet (n  = 40); or a habitual diet (n  = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. Results The high-nutrient-quality ER diet (−8.4 ± 3.2) induced 2.1 kg more weight loss (P  = 0.007) than the low-nutrient-quality ER diet (−6.3 ± 3.9), reduced fasting serum total cholesterol (P  = 0.014) and plasma triglycerides (P  < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. Conclusions A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2006.01.001 Byline: Lydia Afman, Michael Muller Abstract: Until recently, nutrition research concentrated on nutrient deficiencies and impairment of health. The advent of genomics -- interpreted broadly as a suite of high throughput technologies for the generation, processing, and application of scientific information about the composition and functions of genomes -- has created unprecedented opportunities for increasing our understanding of how nutrients modulate gene and protein expression and ultimately influence cellular and organismal metabolism. Nutritional genomics (nutrigenomics), the junction between health, diet, and genomics, can be seen as the combination of molecular nutrition and genomics. The diverse tissue and organ-specific effects of bioactive dietary components include gene-expression patterns (transcriptome); organization of the chromatin (epigenome); protein-expression patterns, including posttranslational modifications (proteome); as well as metabolite profiles (metabolome). Nutrigenomics will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phases of diet-related disease, and the extent to which individual sensitizing genotypes contribute to such diseases. Eventually, nutrigenomics will lead to evidence-based dietary intervention strategies for restoring health and fitness and for preventing diet-related disease. In this review, we provide a brief overview of nutrigenomics from our point of view by describing current strategies, future opportunities, and challenges.

Until recently, nutrition research concentrated on nutrient deficiencies and impairment of health. The advent of genomics--interpreted broadly as a suite of high throughput technologies for the generation, processing, and application of scientific information about the composition and functions of genomes--has created unprecedented opportunities for increasing our understanding of how nutrients modulate gene and protein expression and ultimately influence cellular and organismal metabolism. Nutritional genomics (nutrigenomics), the junction between health, diet, and genomics, can be seen as the combination of molecular nutrition and genomics. The diverse tissue and organ-specific effects of bioactive dietary components include gene-expression patterns (transcriptome); organization of the chromatin (epigenome); protein-expression patterns, including posttranslational modifications (proteome); as well as metabolite profiles (metabolome). Nutrigenomics will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phases of diet-related disease, and the extent to which individual sensitizing genotypes contribute to such diseases. Eventually, nutrigenomics will lead to evidence-based dietary intervention strategies for restoring health and fitness and for preventing diet-related disease. In this review, we provide a brief overview of nutrigenomics from our point of view by describing current strategies, future opportunities, and challenges. J Am Diet Assoc. 2006;106:569-576.