Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery

Background: The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT). Methods: Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed. Results: All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01). Conclusions: Elevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission

Hypoxia and adipose tissue function and dysfunction in obesity

The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signalling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors – the adipokines. Increases in the secretion of a number of adipokines occurs in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in pO2 is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of inflammation-related adipokines is up-regulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilisation is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at pO2 levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity

Feasibility study of portable technology for weight loss and HbA1c control in type 2 diabetes

Background The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM). Methods The intervention was a small wearable mHealth device used over 12 weeks by overweight people with T2DM with the intent to lose weight and reduce their HbA1c level. A 4 week maintenance period using the device followed. The device records physical activity level and information about food consumption, and provides motivational feedback based on energy balance. Twenty-seven participants were randomised to receive no intervention; intervention alone; or intervention plus weekly motivational support. All participants received advice on diet and exercise at the start of the study. Weight and HbA1c levels were recorded at baseline and weeks 6, 12, and 16. Qualitative interviews were conducted with participants who received the intervention to explore their experiences of using the device and involvement in the study including the training received. Results Overall the device was perceived to be well-liked, acceptable, motivational and easy to use by participants. Some logistical changes were required during the feasibility study, including shortening of the study duration and relaxation of participant inclusion criteria. Descriptive statistics of weight and HbA1c data showed promising trends of weight loss and HbA1c reduction in both intervention groups, although this should be interpreted with caution. Conclusions A number of methodological recommendations for a future RCT emerged from the current feasibility study. The mHealth device was acceptable and promising for helping individuals with T2DM to reduce their HbA1c and lose weight. Devices with similar features should be tested further in larger studies which follow these methodological recommendations

Visceral adiposity index and 10-year cardiovascular disease incidence:the ATTICA study

Background and aims: Visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue accumulation/dysfunction. Our aim was to evaluate potential associations between the VAI and the 10-year cardiovascular disease (CVD) incidence. Methods and results: During 2001-2002, 3042 Greek adults (1514 men; age: ≥18 years) without previous CVD were recruited into the ATTICA study, whilst the 10-year study follow-up was performed in 2011-2012, recording the fatal/non-fatal CVD incidence in 2020 (1010 men) participants. The baseline VAI scores for these participants were calculated based on anthropometric and lipid variables, while VAI tertiles were extracted for further analyses. During the study follow-up a total of 317 CVD events (15.7%) were observed. At baseline, the participants' age and the prevalence of hypertension, diabetes, hypercholesterolemia and metabolic syndrome increased significantly across the VAI tertiles. After adjusting for multiple confounders, VAI exhibited a significantly independent positive association with the 10-year CVD incidence (OR = 1.05, 95%CI: 1.01, 1.10), whereas the association of the body mass index (HR = 1.03, 95%CI: 0.99, 1.08), or the waist circumference (HR = 1.01, 95%CI: 0.99, 1.02) was less prominent. Sex-specific analysis further showed that VAI remained significantly predictive of CVD in men alone (HR = 1.06, 95%CI: 1.00, 1.11) but not in women (HR = 1.06, 95%CI: 0.96, 1.10). Conclusions: Our findings show for the first time in a large-sample, long-term, prospective study in Europe that the VAI is independently associated with elevated 10-year CVD risk, particularly in men. This suggests that the VAI may be utilized as an additional indicator of long-term CVD risk for Caucasian/Mediterranean men without previous CVD

The effect of online and in-person team-based learning (TBL) on undergraduate endocrinology teaching during COVID-19 pandemic

Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Copyright © The Author(s) 2022. Background: Team-based learning (TBL) combines active and collaborative learning, while incorporating aspects of the flipped classroom approach and problem-based learning. The COVID-19 pandemic presented certain challenges in the delivery of TBL in class. In this study, we investigated the impact of TBL on the academic performance of final year Biomedical Sciences’ undergraduate students in the context of an “Endocrine Disorders” study block. We did so by comparing the classical in-person approach and online delivery due to the COVID-19 pandemic. Methods: A non-compulsory TBL session was introduced to the curriculum of this block, which followed the traditional 2-h lecture delivery. Comparative analysis was performed for the exam and coursework performance of students who attended the TBL sessions (online and in-person) and those that did not. Results: Both cohorts of students who attended either in-person (n = 66) or online TBL sessions (n = 109) performed significantly better in their exams (p < 0.05) and a related coursework (p < 0.001 and p < 0.05, respectively) when compared to those that did not attend. For both these cohorts the exam mark distribution was much narrower compared to those that did not attend the TBL sessions where the majority of fails and “no shows” were recorded. Conclusions: Online and in-person TBL, can successfully supplement traditional lecture-based teaching and enhance the learning/performance, for complex medical subjects/topics. Our findings demonstrate that it is possible to deliver these sessions online with demonstrable benefit for students suggesting that there is greater flexibility in the use of TBL in higher education

The “Road” to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review

Data Availability Statement: No extra data is generated in this review article.Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR dysregulation in endometriosis and EAOCs, investigating cancer driver gene mutations and their potential interaction with the mTOR pathway. Additionally, we explore the complex pathogenesis of transformation, considering environmental, hormonal, and epigenetic factors. We then discuss postmenopausal endometriosis pathogenesis and propensity for malignant transformation. Finally, we summarize the current advancements in mTOR-targeted therapeutics for endometriosis and EAOCs.This research received no external funding

Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development

The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers?waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin?in mid-life. We used data from the Medical Research Council?s National Survey of Health and Development?the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16?51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn?t have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women

Host cell entry mediators implicated in the cellular tropism of SARS‑CoV‑2, the pathophysiology of COVID‑19 and the identification of microRNAs that can modulate the expression of these mediators (Review)

Copyright: © Katopodis et al. The pathophysiology of coronavirus disease 2019 (COVID‑19) is mainly dependent on the underlying mechanisms that mediate the entry of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) into the host cells of the various human tissues/organs. Recent studies have indicated a higher order of complexity of the mechanisms of infectivity, given that there is a wide‑repertoire of possible cell entry mediators that appear to co‑localise in a cell‑ and tissue‑specific manner. The present study provides an overview of the ‘canonical’ SARS‑CoV‑2 mediators, namely angiotensin converting enzyme 2, transmembrane protease serine 2 and 4, and neuropilin‑1, expanding on the involvement of novel candidates, including glucose‑regulated protein 78, basigin, kidney injury molecule‑1, metabotropic glutamate receptor subtype 2, ADAM metallopeptidase domain 17 (also termed tumour necrosis factor‑α convertase) and Toll‑like receptor 4. Furthermore, emerging data indicate that changes in microRNA (miRNA/miR) expression levels in patients with COVID‑19 are suggestive of further complexity in the regulation of these viral mediators. An in silico analysis revealed 160 candidate miRNAs with potential strong binding capacity in the aforementioned genes. Future studies should concentrate on elucidating the association between the cellular tropism of the SARS‑CoV‑2 cell entry mediators and the mechanisms through which they might affect the clinical outcome. Finally, the clinical utility as a biomarker or therapeutic target of miRNAs in the context of COVID‑19 warrants further investigation