Showing papers by "Arne Astrup published in 2023"

An integrated single cell and spatial transcriptomic map of human white adipose tissue

Abstract: To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.

Weight loss relapse associated with exposure to perfluorinated alkylate substances

Abstract: The purpose of this study was to test the hypothesis that perfluorinated alkylate substance (PFAS) exposures are associated with body weight increases in a dietary intervention study.

Gestational weight gain in women with pre-pregnancy overweight or obesity and anthropometry of infants at birth

Abstract: Objective To examine the association of gestational weight gain (GWG) among women with pre-pregnancy overweight or obesity with infant weight and BMI z-score at birth. Methods This study is a secondary analysis of a randomized controlled trial including data from 208 infants at birth born by mothers with pre-pregnancy BMI between 28 and 45 kg/m2 who completed the APPROACH study (randomized to a high-protein low-glycemic index diet or a moderate-protein moderate-glycemic index diet). This analysis pooled the two diet treatment groups together and data were analyzed using a linear mixed model. Results Limiting GWG by 1 kg was associated with lower birthweight (−16 g, P = 0.003), BMI z-score (−0.03SD, P = 0.019), weight z-score (−0.03SD, P = 0.004), and infant abdominal circumference (−0.06 cm, P = 0.039). Infants born by mothers whose GWG was ≤9 kg weighed less (122 g, 95% CI: 6–249, P = 0.040), had similar BMI z-score (0.2SD, 95% CI: −0.06 to 0.55, P = 0.120), and lower incidence of emergency cesarean deliveries (11.5% vs. 23.1%, P = 0.044) compared to infants born by mothers whose GWG was >9 kg. When women were classified into GWG quartiles, women in Q1 (GWG range: −7.0 to 3.2 kg) gave birth to smaller infants (3,420 g, P = 0.015) with lower BMI z-score (−0.5SD, P = 0.041) than women in Q2 (3.3–7.1 kg), Q3 (7.2–10.9 kg) and Q4 (11.1–30.2 kg). Conclusions Limiting GWG among women with pre-pregnancy overweight or obesity was associated with lower infant weight, BMI z-score, weight z-score, and abdominal circumference at birth. Moreover, GWG below the Institute of Medicine guideline of a maximum of 9 kg was associated with lower birthweight and fewer emergency cesarean deliveries.

#2971 long-term effects of the new nordic renal diet on phosphorous homeostasis in patients with chronic kidney disease stage 3 and 4

Abstract: Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. The New Nordic Renal Diet (NNRD) is a whole food approach designed by our group, with low dietary phosphorus content (850 mg/day). In a 1-week study, NNRD had positive effects on phosphorus homeostasis in patients with CKD stage 3-4 [1]. The aim of the present study was to examine the long-term health effects of a dietary intervention with NNRD in patients with CKD stage 3-4 [2]. A 26-week randomized, controlled, non-blinded trial comparing the effect of NNRD vs. non-restricted habitual diet. Patients in the NNRD group received weekly home delivery of fresh food items (free of charge) and recipes for five days of the week, and on the remaining two days they were instructed to prepare meals according to the NNRD food principles. The study was designed with seven follow-up visits in the outpatient clinic where fasting blood samples and 24-hour urine collection were delivered. Linear mixed-effects models were used to assess the effects of the intervention, time, and the potential interaction between intervention and time. The primary endpoint was the difference in 24-hour urine phosphorus excretion between the two study groups. Secondary endpoints included fractional phosphorus excretion and plasma fibroblast growth factor 23 (p-FGF23). Sixty patients (mean age 54 years, 31 women) with mean eGFR of 34 ml/min/1.73 m2 were included. Two patients were withdrawn due to dialysis initiation. In the NNRD-group (n = 29), mean 24-hour urine phosphorus excretion during the intervention period was 651 mg (SD, 35 mg) vs. 930 mg (SD, 84 mg) in the control group (n = 29), between-group difference 279 (95% CI; -372, -91; P < 0.001) (Figure 1). Mean fractional phosphorus excretion was 11% (SD, 5%) in the NNRD-group and 14% (SD, 7%) in the control group, between-group difference 3% (95% CI; -6.4, -0.8; P = 0.01). Mean p-FGF23 was 162 pg/ml (SD, 130 pg/ml) in the NNRD-group and 215 pg/ml (SD, 230 pg/ml) in the control group, between-group difference 52 pg/ml (95% CI; -100, 73; P = 0.03). P-urea was 3.4 mmol/L lower in the NNRD group (95% CI; -5.3, -0.2, P = 0.03). P-albumin was 1.1 g/L higher in the NNRD group (95% CI; 0.02, 2.4; P = 0.04) and 24-h urine bicarbonate excretion was 4.1 mmol higher in the NNRD group (95% CI; 0.7, 7.5, P = 0.01). There was no difference between study groups in p-phosphorous, p-creatinine, p-potassium, p-calcium, p-lipids, or proteinuria. NNRD intervention in the context of fresh food delivery and recipes was feasible and had a major beneficial effect on phosphorous parameters in patients with CKD 3-4.

Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity.

Abstract: OBJECTIVE The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, whether PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms. RESEARCH DESIGN AND METHODS Genetic association analyses comprised up to 19,585 individuals. PA was self-reported, and IS was defined based on inverted HOMA insulin resistance index. Functional analyses were performed in muscle biopsies from 140 men, and in cultured muscle cells. RESULTS The BMI-increasing effect of the FTO rs9939609 A allele was attenuated by 47% with high PA (β [SE], -0.32 [0.10] kg/m2, P = 0.0013), and by 51% with high IS (-0.31 [0.09] kg/m2, P = 0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 [0.09] kg/m2, P = 0.023; IS, -0.28 [0.09] kg/m2, P = 0.0011). The rs9939609 A allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, P > 0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A allele was associated with higher expression of FTO in skeletal muscle tissue (0.03 [0.01], P = 0.011), and in skeletal muscle cells, we identified a physical interaction between the FTO promoter and an enhancer region encompassing rs9939609. CONCLUSIONS Greater PA and IS independently reduced the effect of rs9939609 on obesity. These effects might be mediated through altered expression of FTO in skeletal muscle. Our results indicated that PA and/or other means of increasing insulin sensitivity could counteract FTO-related genetic predisposition to obesity.

Prevention and management of obesity in a lifetime perspective.

Abstract: The prevalence of obesity is increasing across all geographies. Obesity develops due to a disruption of the energy balance regulation. However, the cause is not well understood. Identification of causal factors that may be modified is crucial to reduce the prevalence of obesity. However, the interventions needed will likely differ between life stages. Hence, obesity research should span from pre-conception to adulthood. In this review, we point to gaps and limitations in existing research, highlight recently initiated studies from which we are awaiting results and point to future directions.

Baseline gene expression in subcutaneous adipose tissue predicts diet-induced weight loss in individuals with obesity

Abstract: Background Weight loss effectively reduces cardiometabolic health risks among people with overweight and obesity, but inter-individual variability in weight loss maintenance is large. Here we studied whether baseline gene expression in subcutaneous adipose tissue predicts diet-induced weight loss success. Methods Within the 8-month multicenter dietary intervention study DiOGenes, we classified a low weight-losers (low-WL) group and a high-WL group based on median weight loss percentage (9.9%) from 281 individuals. Using RNA sequencing, we identified the significantly differentially expressed genes between high-WL and low-WL at baseline and their enriched pathways. We used this information together with support vector machines with linear kernel to build classifier models that predict the weight loss classes. Results Prediction models based on a selection of genes that are associated with the discovered pathways ‘lipid metabolism’ (max AUC = 0.74, 95% CI [0.62–0.86]) and ‘response to virus’ (max AUC = 0.72, 95% CI [0.61–0.83]) predicted the weight-loss classes high-WL/low-WL significantly better than models based on randomly selected genes (P < 0.01). The performance of the models based on ‘response to virus’ genes is highly dependent on those genes that are also associated with lipid metabolism. Incorporation of baseline clinical factors into these models did not noticeably enhance the model performance in most of the runs. This study demonstrates that baseline adipose tissue gene expression data, together with supervised machine learning, facilitates the characterization of the determinants of successful weight loss.

Human blood plasma biomarkers of diet and weight loss among centrally obese subjects in a New Nordic Diet intervention

Abstract: Scope The New Nordic Diet (NND) has been shown to promote weight loss and lower blood pressure amongst obese people. This study investigates blood plasma metabolite and lipoprotein biomarkers differentiating subjects who followed Average Danish Diet (ADD) or NND. The study also evaluates how the individual response to the diet is reflected in the metabolic differences between NND subjects who lost or maintained their pre-intervention weight. Methods Centrally obese Danes (BMI >25) followed NND (90 subjects) or ADD (56 subjects) for 6 months. Fasting blood plasma samples, collected at three time-points during the intervention, were screened for metabolites and lipoproteins (LPs) using proton nuclear magnetic resonance spectroscopy. In total, 154 metabolites and 65 lipoproteins were analysed. Results The NND showed a relatively small but significant effect on the plasma metabolome and lipoprotein profiles, with explained variations ranging from 0.6% for lipoproteins to 4.8% for metabolites. A total of 38 metabolites and 11 lipoproteins were found to be affected by the NND. The primary biomarkers differentiating the two diets were found to be HDL-1 cholesterol, apolipoprotein A1, phospholipids, and ketone bodies (3-hydroxybutyric acid, acetone, and acetoacetic acid). The increased levels of ketone bodies detected in the NND group inversely associated with the decrease in diastolic blood pressure of the NND subjects. The study also showed that body weight loss among the NND subjects was weakly associated with plasma levels of citrate. Conclusion The main plasma metabolites associated with NND were acetate, methanol and 3-hydroxybutyrate. The metabolic changes associated with the NND-driven weight loss are mostly pronounced in energy and lipid metabolism.

Postprandial Glycaemia, Insulinemia, and Lipidemia after 12 Weeks’ Cheese Consumption: An Exploratory Randomized Controlled Human Sub-Study

Abstract: Some populations are recommended to consume low-fat dairy, although the evidence behind replacing high-fat with low-fat dairy products is limited. This exploratory sub-study investigated the effect of cheese with different fat content on postprandial changes in type-2-diabetes risk markers. Following 12-week cheese or jam intake, a 4 h meal test was conducted with 37 participants. Test meals included bread and either: 80 g regular-fat cheese (REG), 80 g reduced-fat cheese (RED) or 25 g jam (CHO). Postprandial blood was drawn and appetite sensations registered. Time-meal interactions were not observed for glucose and insulin, but for triglycerides (TG) and free fatty acids (FFA). Pairwise comparisons showed 0.17 ± 0.07 mmol/L (p = 0.044) and 0.25 ± 0.07 mmol/L (p = 0.002) higher TG at 180 and 240 min, respectively, and 94 ± 37 mmol/L (p = 0.029) higher FFA at 180 min for REG compared with RED. Compared with CHO, intake of both cheese meals reduced insulin and glucose (main effects of meal, both p ≤ 0.011) and increased FFA and TG at certain time points. In conclusion, intake of cheese with a regular, compared with reduced, fat content did not affect glucose, insulin and appetite, but increased TG and FFA.