Primary discharge diagnosis codes according to ICD-10 chapters.

<p>Primary discharge diagnosis codes according to ICD-10 chapters.</p

Selected reasons for acute inpatient admission (first-listed diagnosis codes), by BMI category.

<p>Selected reasons for acute inpatient admission (first-listed diagnosis codes), by BMI category.</p

Body Mass Index of 92,027 patients acutely admitted to general hospitals in Denmark: Associated clinical characteristics and 30-day mortality

<div><p>Background</p><p>Data are sparse on the range of BMI among patients acutely admitted to general hospitals. We investigated BMI values and associated patient characteristics, reasons for hospital admission, and mortality in Denmark.</p><p>Methods</p><p>We identified all persons with an acute inpatient admission 2011–2014 in Central Denmark Region and assessed BMI measurements recorded in the Clinical Information System. We used cross-sectional and cohort analyses to examine the BMI distribution and its association with demographic characteristics, comorbidities, medication use, tobacco smoking, reasons for admission, and 30-day mortality.</p><p>Results</p><p>Among 92,027 acutely admitted patients (median age 62 years, 49% female) with a BMI measurement, 4% had a BMI (kg/m²) <18.5, 42% a BMI between 18.5 and 25, 34% a BMI between 25 and 30, and 20% a BMI ≥30. Compared with normal-weight patients, 30-day mortality was high among patients with BMI <18.5 (7.5% vs. 2.8%, age- and smoking-adjusted odds ratio (aOR) 2.4; 95% confidence interval (CI): 2.0–2.9, whereas patients with overweight (aOR 0.7; 95% CI: 0.6–0.8) and obesity class I (aOR 0.8; 95% CI: 0.6–0.9)). Compared with the total population, patients with BMI <18.5 were older (68 years median); more were female (73%); more had comorbidities (Charlson Comorbidity Index score >0 in 42% vs. 33% overall), more were current smokers (45% vs. 27% overall), and acute admissions due to respiratory diseases or femoral fractures were frequent. In contrast, patients with BMI ≥30 were relatively young (59 years median), fewer smoked (24%): type 2 diabetes, sleep disorders, cholelithiasis, and heart failure were frequent diagnoses. Prevalence of therapies for metabolic syndrome, pain, and psychiatric disorders increased with higher BMI, while patients with BMI <18.5 frequently used asthma medications, glucocorticoids, and antibiotics.</p><p>Conclusion</p><p>In patients acutely admitted to general hospitals, reasons for hospital admission and associated clinical characteristics differ substantially according to BMI range. BMI <18.5 is a clinical predictor of high short-term mortality.</p></div

Mortality odds ratios (ORs), using normal weight as reference.

<p>Mortality odds ratios (ORs), using normal weight as reference.</p

Prevalence ratios (PRs) of discharge diagnosis codes according to ICD-10 chapters.

<p>Prevalence ratios (PRs) of discharge diagnosis codes according to ICD-10 chapters.</p

Current use of selected prescription drugs, by BMI category.

<p>Current use of selected prescription drugs, by BMI category.</p

Characteristics of 92,027 patients acutely admitted to hospital in the Central Denmark Region between 2011 and 2014.

<p>Characteristics of 92,027 patients acutely admitted to hospital in the Central Denmark Region between 2011 and 2014.</p

Conversion of mature TERT-hWA adipocytes into brown-like adipocytes upon exposure to rosiglitazone.

<p><b>(A)</b> The rosiglitazone-induced browning protocol. <b>(B)</b> Relative mRNA levels of <i>UCP1</i> in mature TERT-hWA adipocytes (day 15, passage 7–14), SGBS and hMADS adipocytes exposed to vehicle or 1 μM rosiglitazone from day 12 to 15. <b>(C)</b> Protein levels of UCP1 in TERT-hWA adipocytes (day 15, passage 13) exposed to vehicle or 1 μM rosiglitazone from day 12 to 15. TFIIB was used as a loading control. <b>(D)</b> Relative mRNA levels of the thermogenesis-related genes <i>EBF2</i>, <i>DIO2</i> and <i>PDK4</i> in mature TERT-hWA adipocytes (day 15, passage 12) exposed to vehicle or 1 μM rosiglitazone from day 12 to 15. <b>(E)</b> Relative mRNA levels of the β-adrenoceptors <i>ADRB1-3</i> in mature TERT-hWA adipocytes (day 15, passage 12) exposed to vehicle or 1 μM rosiglitazone from day 12 to 15. <b>(F)</b> Relative mRNA levels of the mitochondrial markers <i>CPT1B</i>, <i>CS</i> and <i>COXII</i> in mature TERT-hWA adipocytes (day 15, passage 12) exposed to vehicle or 1 μM rosiglitazone from day 12 to 15. In (B) and (D-F), expression levels were normalized to <i>TBP</i> levels. The normalized expression in vehicle-treated cells was set to 1. Data are presented as mean +SEM of one representative experiment done in technical triplicate. Statistical significance was determined by unpaired two-tailed Student’s t-test. *, p < 0.05 versus vehicle-treated cells.</p

Characterization of immortalized human brown and white pre-adipocyte cell models from a single donor

<div><p>Brown adipose tissue with its constituent brown adipocytes is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. The molecular control of brown adipocyte differentiation and function has been extensively studied in mice, but relatively little is known about such regulatory mechanisms in humans, which in part is due to lack of human brown adipose tissue derived cell models. Here, we used retrovirus-mediated overexpression to stably integrate human telomerase reverse transcriptase (TERT) into stromal-vascular cell fractions from deep and superficial human neck adipose tissue biopsies from the same donor. The brown and white pre-adipocyte cell models (TERT-hBA and TERT-hWA, respectively) displayed a stable proliferation rate and differentiation until at least passage 20. Mature TERT-hBA adipocytes expressed higher levels of thermogenic marker genes and displayed a higher maximal respiratory capacity than mature TERT-hWA adipocytes. TERT-hBA adipocytes were UCP1-positive and responded to β-adrenergic stimulation by activating the PKA-MKK3/6-p38 MAPK signaling module and increasing thermogenic gene expression and oxygen consumption. Mature TERT-hWA adipocytes underwent efficient rosiglitazone-induced ‘browning’, as demonstrated by strongly increased expression of UCP1 and other brown adipocyte-enriched genes. In summary, the TERT-hBA and TERT-hWA cell models represent useful tools to obtain a better understanding of the molecular control of human brown and white adipocyte differentiation and function as well as of browning of human white adipocytes.</p></div

Response to β-adrenergic stimulation.

<p><b>(A)</b> Relative mRNA levels of the β-adrenoceptors <i>ADRB1-3</i> in mature TERT-hBA and TERT-hWA adipocytes at passage 10, 15 and 20. Expression levels were normalized to <i>TBP</i> levels. The normalized expression in TERT-hWA adipocytes was set to 1. RT-qPCR data are presented as mean of means +SEM from 5 independent experiments (two experiments in passage 10 and passage 15 and one experiment in passage 20). Statistical significance was determined by paired two-tailed Student’s t-test. *, p < 0.05 versus TERT-hWA. <b>(B)</b> Relative mRNA levels of thermogenic genes in mature TERT-hBA adipocytes (day 12, passage 12) stimulated with 0.1 μM ISO for 6 h. <b>(C)</b> Relative mRNA levels of thermogenic genes in mature TERT-hBA adipocytes (day 12, passage 13) stimulated with 10 μM FSK for 6 h. In (B) and (C), expression levels were normalized to <i>TBP</i> levels. The normalized expression in vehicle-treated cells was set to 1. Data are presented as mean +SEM of one representative experiment done in technical triplicate. Statistical significance was determined by unpaired two-tailed Student’s t-test. *, p < 0.05 versus vehicle-treated cells. <b>(D)</b> UCP1 protein levels in mature TERT-hBA [day 12, passage 10 (P10) and 15 (P15)] stimulated with 0.1 μM ISO for 24 h. TFIIB was used as a loading control. <b>(E)</b> Western blot analysis for phosphorylated adipocyte mediators in mature TERT-hBA adipocytes (day 12, P9) pretreated with 10 μM propranolol or vehicle for 1 h before being stimulated with 10 μM FSK or 0.1 μM ISO for an additional 1 h. <b>(F-G)</b> Representative time course of oxygen consumption and extracellular acidification rates (OCR and ECAR, respectively) in mature TERT-hBA adipocytes (day 12, passage 9) before and after injection of 10 μM ISO or 10 μM FSK. Data are presented as mean +/- SEM of one representative experiment with 9–12 wells per condition. (H) Western blot analysis for phosphorylated HSL in mature TERT-hWA adipocytes (day 12, passage 9) pretreated with 10 μM propranolol or vehicle for 1 h before being stimulated with 10 μM FSK or 0.1 μM ISO for an additional 1 h.</p