Publications
259 results found
Ortega PM, Bansi D, Kaur V, et al., 2022, Utility of the Apollo OverStitch Device for the endoscopic revision of the gastro-jejunal stoma in patients with weight regain after Roux-en-Y gastric bypass (RYGB), Publisher: SPRINGER, Pages: 22-22, ISSN: 0960-8923
Patel P, Thomas R, Hamady M, et al., 2022, Simulation training to create the gold standard framework to run the EMBIO trial (left gastric artery embolisation vs placebo), a double blinded, multi-centre, randomised controlled trial., 13th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: 27-27, ISSN: 0960-8923
Patel P, Thomas R, Hamady M, et al., 2022, What we know about left gastric artery embolisation and will EMBIO provide the next solution to treat obesity?, Publisher: SPRINGER, Pages: 26-27, ISSN: 0960-8923
Shibib L, Al-Qaisi M, Ahmed A, et al., 2022, Reversal and remission of T2DM - an update for practitioners, Vascular Health and Risk Management, Vol: 18, Pages: 417-443, ISSN: 1176-6344
Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines.
Lam K, Nazarian S, Gadi N, et al., 2022, Patient perspectives on surgeon-specific outcome reports in bariatric surgery, Surgery for Obesity and Related Diseases, Vol: 18, Pages: 704-713, ISSN: 1550-7289
BACKGROUND: Surgeon specific outcome reports (SSOR) in the UK can be accessed freely by the general public to promote transparency and informed decision-making. However, the views amongst bariatric patients concerning these data are unknown. OBJECTIVES: The aims of this study were to determine patient awareness, views and priorities for outcome reporting in bariatric surgery, and to provide recommendations for future surgeon-specific outcome reporting through the United Kingdom National Bariatric Surgery Registry. SETTING: Bariatric surgical unit in a UK university teaching hospital. METHODS: We adapted a previously validated questionnaire and surveyed the views of 150 patients in a single bariatric surgical unit. We collected data concerning awareness, views, and future priorities for outcome reporting. RESULTS: A full 73% of participants were unaware they could access SSOR. Of the participants that were unaware, 75% stated that they would have accessed SSOR had they been aware they could. Of the participants that had previously accessed SSOR, 86% stated they understood the data, although 61% indicated it did not influence their choice of surgeon. The majority of participants favored public release of outcome reports at the surgeon-level (75%) and hospital-level (83%). The 3 main priorities indicated by participants for future outcome reporting were complication rates (91%), patient reported outcome measures (90%), and reoperation rate (89%), all at the surgeon level. CONCLUSION: Patient awareness of outcome reporting is poor. Efforts must be made to increase awareness of SSOR. Patients should be incorporated as key stakeholders in determining future outcome reporting in bariatric surgery.
Ruban A, Miras A, glaysher M, et al., 2022, Duodenal-jejunal bypass liner for the management of Type 2 diabetes and obesity: a multicenter randomized controlled trial, Annals of Surgery, Vol: 275, Pages: 440-447, ISSN: 0003-4932
Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary Background Data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial Registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research
Kenkre JS, Malallah K, Davies I, et al., 2022, Patients with liver fibrosis may be less likely to remit from type 2 diabetes following bariatric surgery, Publisher: WILEY, ISSN: 0742-3071
Cousin E, Duncan BB, Stein C, et al., 2022, Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019, The Lancet Diabetes & Endocrinology, Vol: 10, Pages: 177-192, ISSN: 2213-8587
BackgroundDiabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.MethodsWe used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals.FindingsIn 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−
Jones B, Sands C, Alexiadou K, et al., 2022, The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction, Journal of Clinical Endocrinology and Metabolism, Vol: 107, Pages: e767-e782, ISSN: 0021-972X
Context: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis, and are thought to contribute to the glucose-lowering effects of bariatric surgery. Objective: To establish the metabolomic effects of a combined infusion of GLP-1, OXM and PYY (tripeptide “GOP”) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). Design and setting: Sub-analysis of a single-blind, randomised, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. Patients and interventions: 25 obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n=14) or 0.9% saline control (SAL; n=11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. Main outcome measures: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modelling approaches to identify similarities and differences between the effects of each intervention. Results: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. Conclusions: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.
Wiggins T, Jamel S, Hakky S, et al., 2022, Assurance of surgical quality within multicenter randomized controlled trials for bariatric and metabolic surgery: a systematic review, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: ELSEVIER SCIENCE INC, Pages: 124-132, ISSN: 1550-7289
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- Citations: 1
McLean KA, Kamarajah SK, Chaudhry D, et al., 2021, Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 1448-1464, ISSN: 0007-1323
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- Citations: 7
Tankel J, Ahmed AR, 2021, Gastrojejunostomy in Roux-En-Y Gastric Bypass for Morbid Obesity: Linear Stapler Length Does Not Affect Mid-term Outcomes, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 794-798, ISSN: 1530-4515
Ortega PM, Ahmed A, Valencia JM, 2021, Managing severe abdominal pain 3 years after RYGB: resection of marginal ulcer and primary GJ reconstruction, 12th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S12-S12, ISSN: 0960-8923
Patel K, Aggarwal R, Martin G, et al., 2021, Feasibility of a multi-parametric continuous monitoring wearable device in patients undergoing bariatric surgery, 12th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S12-S12, ISSN: 0960-8923
Davies I, Kenkre J, Alexiadou K, et al., 2021, Can current methods of predicting T2D remission following metabolic surgery be improved?, 12th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S13-S13, ISSN: 0960-8923
Glasbey J, Ademuyiwa A, Adisa A, et al., 2021, Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study, The Lancet Oncology, Vol: 22, Pages: 1507-1517, ISSN: 1470-2045
BackgroundSurgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.MethodsThis international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.FindingsOf eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notif
Ortega PM, Ahmed A, Bansi D, et al., 2021, Duodenal switch revision: importance of intraoperative endoscopy, 12th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S11-S12, ISSN: 0960-8923
Ghanem A, Ahmed A, 2021, Revision of failed Vertical Banded Gastroplasty (VBG) to Roux-en-Y Gastric Bypass (RYGB), 12th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S11-S11, ISSN: 0960-8923
Malallah K, Alexiadou K, Tabbakh Y, et al., 2021, Roux-en-Y gastric bypass and Sleeve Gastrectomy exhibit energy expenditure equally one-year post-surgery, 12th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S8-S9, ISSN: 0960-8923
Eslam M, Ahmed A, Despres J-P, et al., 2021, Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 6, Pages: 743-753
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- Citations: 46
Moussa O, Ortega P, Mansour S, et al., 2021, Bariatric surgical services within a pandemic can continue safely: the initial experience of a UK centre of excellence., Obesity Surgery, ISSN: 0960-8923
Salem V, Demetriou L, Behary P, et al., 2021, Weight loss by low calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns: an functional MRI study, Diabetes Care, Vol: 44, Pages: 1842-1851, ISSN: 0149-5992
OBJECTIVE: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.RESEARCH DESIGN AND METHODS: Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups.RESULTS: We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2) VLCD resulted in higher neural activation of cognitive control regions in response to food cues associated with exercising increased cognitive restraint over eating, whereas RYGB did not; and 3) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD.CONCLUSIONS: Taken together, these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast to enduring weight loss after RYGB.
Ahmed A, Morales-Conde S, Legrand M, et al., 2021, Clinical outcomes of pre-attached reinforced stapler reloads in bariatric surgery: A prospective case series, INTERNATIONAL JOURNAL OF SURGERY OPEN, Vol: 32, ISSN: 2405-8572
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- Citations: 1
Samarasinghe S, Sudlow A, Dimitriadis GK, et al., 2021, Simple tool to prioritize access to bariatric surgery for people living with obesity during the COVID-19 pandemic, British Journal of Surgery, Vol: 108, Pages: e179-e180, ISSN: 0007-1323
Ghanem A, Emile S, Cousins J, et al., 2021, Bariatric surgery during COVID-19 in the UK: a British obesity and metabolic surgery society (BOMSS) survey, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 36, Pages: 533-543, ISSN: 0930-2794
BackgroundAfter the declaration of COVID-19 as a pandemic last March 2020, several adjustments in surgical services were implemented. Plans are now being formulated for restarting bariatric surgery. The aim of this survey is to capture the practice during the pandemic and the readiness to restart to provide a framework to deal with the backlog of bariatric cases.MethodA survey was delivered to consultant surgeon members of the British Obesity and Metabolic Surgery Society and non-bariatric surgery consultant members of the Association of Upper GI Surgeons.ResultsThe survey elicited a response rate of 40% (n = 66) among bariatric surgeons and 15.5% (n = 34) between non-bariatric surgeons. The average question response rate was 93% (88–100%). Most of the elective bariatric surgeries and clinics were cancelled early after declaration of the pandemic. Remote technologies for patient education evolved and were used heavily during the pandemic. The average cancelled elective bariatric surgery operations per week was 9. Nearly a quarter of responders reported performing emergency bariatric surgery during the pandemic. Most of the bariatric surgeons reported being ready to restart the service within 1–2 months. Responders recommended using private sector beds to increase NHS capacity and using the link between obesity and poor COVID-19 outcomes to push for prioritisation of bariatric patients.ConclusionThis survey is an attempt to understand the impact of COVID-19 on UK bariatric service and the preparedness to restart. It expressed the bariatric surgery consultants’ view of prioritisation of bariatric patients on clinical basis rather than the first-come-first-served basis.
Kenkre J, Ahmed A, Purkayastha S, et al., 2021, Who will benefit from bariatric surgery for diabetes? A protocol for an observational cohort study, BMJ Open, Vol: 11, ISSN: 2044-6055
Introduction Type 2 diabetes mellitus (T2DM) and obesity are pandemic diseases that lead to a great deal of morbidity and mortality. The most effective treatment for obesity and T2DM is bariatric or metabolic surgery; it can lead to long-term diabetes remission with 4 in 10 of those undergoing surgery having normal blood glucose on no medication 1 year postoperatively. However, surgery carries risks and, additionally, due to resource limitations, there is a restricted number of patients who can access this treatment. Moreover, not all those who undertake surgery respond equally well metabolically. The objective of the current research is to prospectively investigate predictors of T2DM response following metabolic surgery, including those directly involved in its aetiopathogenesis such as fat distribution and genetic variants. This will inform development of a clinically applicable model to help prioritise this therapy to those predicted to have remission.Methods and analysis A prospective multicentre observational cohort study of adult patients with T2DM and obesity undergoing Roux-en-Y gastric bypass surgery. Patients will be comprehensively assessed before surgery to determine their clinical, metabolic, psychological, genetic and fat distribution profiles. A multivariate logistic regression model will be used to assess the value of the factors derived from the preoperative assessment in terms of prediction of diabetes remission.Ethics and dissemination Formal ethics review was undertaken with a favourable opinion (UK HRA RES reference number 18/LO/0931). The dissemination plan is to present the results at conferences, in peer-reviewed journals as well as to lay media and to patient organisations.Trial registration details ClinicalTrials.gov, Identifier: NCT03842475.
Ilesanmi I, Tharakan G, Alexiadou K, et al., 2021, Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study, DIABETES CARE, Vol: 44, Pages: 614-617, ISSN: 0149-5992
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- Citations: 8
Miras A, Kamocka A, Pérez-Pevida B, et al., 2021, The effect of standard versus longer intestinal bypass on GLP-1 regulation and glucose metabolism in patients with type 2 diabetes undergoing roux-en-Y gastric bypass. The long-limb study, Diabetes Care, Vol: 44, Pages: 1-9, ISSN: 0149-5992
ObjectiveRoux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.Research Design and MethodsFifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.ResultsBoth groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. ConclusionThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.
McGlone ER, Malallah K, Cuenco J, et al., 2021, DIFFERENTIAL EFFECTS OF BILE ACIDS ON THE POST-PRANDIAL SECRETION OF GUT HORMONES: a randomised crossover study., Am J Physiol Endocrinol Metab
AIMS Bile acids (BA) regulate post-prandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The post-prandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effect of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on post-prandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon and ghrelin. METHODS Twelve healthy volunteers underwent a mixed meal test 60 minutes after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg) or no BA in a randomised cross-over study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin and fibroblast growth factor 19 were measured prior to BA administration at -60, 0 (just prior to mixed meal) and 15, 30, 60, 120, 180 and 240 minutes after the meal. RESULTS UDCA and CDCA provoked differential gut hormone responses: UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced post-prandial secretion of GIP, with an associated reduction in post-prandial insulin secretion. CONCLUSIONS Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmedin obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions.
Lerner A, Kewada D, Ahmed A, et al., 2021, Androgen reduces mitochondrial respiration in mouse brown adipocytes: a model for disordered energy balance in polycystic ovary syndrome, International Journal of Molecular Sciences, Vol: 22, ISSN: 1422-0067
Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including reduced postprandial thermogenesis. Although abnormalities in adipose tissue function have been widely reported in women with PCOS, less is known about direct effects of androgen on white and, particularly, brown adipocytes. The purpose of this study was to investigate the effect of the nonaromatizable androgen dihydrotestosterone (DHT) on (1) lipid accumulation and expression of adipogenic markers in immortalized mouse brown adipose cell lines (IMBATs), (2) mitochondrial respiration in IMBATs, (3) mitochondrial DNA content and gene expression, (4) expression of brown adipose tissue (BAT) markers and thermogenic activation. In addition, we profiled the relative levels of 38 adipokines secreted from BAT explants and looked at androgen effects on adipokine gene expression in both IMBATs and immortalized mouse white adipose (IMWATs) cell lines. Androgen treatment inhibited IMBAT differentiation in a dose-dependent manner, reduced markers of adipogenesis, and attenuated the β-adrenoceptor-stimulated increase in uncoupling protein-1 (UCP1) expression. In explants of mouse interscapular BAT, androgen reduced expression of UCP1, peroxisome proliferator-activated receptor-γ coactivator-1 (PCG-1) and Cidea. Significantly, as well as affecting genes involved in thermogenesis in BAT, androgen treatment reduced mitochondrial respiration in IMBATs, as measured by the Seahorse XF method. The results of this study suggest a role for excess androgen in inhibiting brown adipogenesis, attenuating the activation of thermogenesis and reducing mitochondrial respiration in BAT. Together, these data provide a plausible molecular mechanism that may contribute to reduced postprandial thermogenesis and the tendency to obesity in women with PCOS.
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