Obesity is an escalating global chronic disease. Bariatric surgery is a very efficacious treatment for obesity and its comorbidities. Alterations to gastrointestinal anatomy during bariatric surgery ...result in neurological and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut microbiota, which coalesce to exert a profound influence on eating behavior. A thorough understanding of the mechanisms underlying eating behavior is essential in the management of patients after bariatric surgery. Studies investigating candidate mechanisms have expanded dramatically in the last decade. Herein we review the proposed mechanisms governing changes in eating behavior, food intake, and body weight after bariatric surgery. Additive or synergistic effects of both conditioned and unconditioned factors likely account for the complete picture of changes in eating behavior. Considered application of strategies designed to support the underlying principles governing changes in eating behavior holds promise as a means of optimizing responses to surgery and long-term outcomes.
Obesity and its repercussions constitute an important source of morbidity, impaired quality of life and its complications can have a major bearing on life expectancy. The present article summarizes ...the most important co-morbidities of obesity and their prevalence. Furthermore, it describes classification and grading systems that can be used to assess the individual and combined impact of co-morbid conditions on mortality risk. The literature was screened for assessment tools that can be deployed in the quantification of morbidity and mortality risk in individual patients. Thirteen specific domains have been identified that account for morbidity and mortality in obesity. Cardiovascular disease (CVD) and cancer account for the greatest mortality risk associated with obesity. The King's Criteria and Edmonton Obesity Staging System (EOSS) were identified as useful tools for the detection and monitoring of individual patient mortality risk in obesity care. The stark facts on the complications of obesity should be capitalized on to improve patient management and knowledge and referred to in the wider dissemination of public health messages aimed at improving primary prevention.
Bariatric surgery is an effective therapy for obesity, hypertension and type 2 diabetes mellitus that is refractory to maximal medical therapy. Results of long-term cohort studies and emerging ...evidence from randomized clinical trials have revealed that, in addition to its beneficial effects on weight reduction, blood pressure and metabolic control, bariatric surgery might reduce the incidence and long-term progression of chronic kidney disease (CKD). Preclinical studies have provided experimental verification that bariatric surgery improves key parameters of kidney injury at the functional, structural and ultrastructural levels, and effects a programme of transcriptomic change in the kidney that is coherent with injury resolution. Multiple mechanisms explain these observations, ranging from predictable aspects of risk-factor reduction to some novel and unforeseen renoprotective benefits of surgery. Current evidence therefore supports the judicious use of bariatric surgery to treat patients with obesity, diabetes and CKD. Optimizing the benefits of surgery requires careful patient selection and consideration of how to identify and mitigate some of the challenges associated with these surgical procedures.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific ...hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg/kg, fenofibrate 100mg/kg, ramipril 1mg/kg, rosuvastatin 10mg/kg and subcutaneous liraglutide 0.2mg/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Recovery from DSS-induced colitis is associated with anxiety/depressive-like behaviours in rats.•DSS-induced colitis provokes persistent co-localised iNOS and microglial activation.•Increased ...ventricular volume and reduced cortical T2 relaxometry times following DSS-induced colitis.•Chronic activation of the raphe and nucleus accumbens is evident following DSS-induced colitis.
Depression and anxiety-related psychological symptoms are increasingly recognised as important co-morbidities in patients with inflammatory bowel disease (IBD). Dextran sulfate sodium (DSS) -induced colitis is an animal model of IBD in which afferent activation of the gut-brain axis can be assessed and explored as a source of behavioural change.
Exposure of adult male Wistar rats to DSS (5%) in drinking water induced distal colitis. In parallel to local inflammatory responses in the gut wall, increased expression of IL-6 and iNOS was found in the cerebral cortex and an increase in ventricular volume. Immunoreactivity of immediate early gene FosB/ΔFosB activation was measured as an index of cellular activation and was increased in the nucleus accumbens and dorsal raphe nucleus in acutely colitic animals. Following resolution of the acute colitic response, sustained anhedonia in the saccharin preference test, immobility in the forced swim test, reduced burying behaviour in the marble burying test, and mild signs of anxiety in the elevated plus maze and light/dark box were observed. Central increases in iNOS expression persisted during the recovery phase and mapped to reactive microglia, particularly those found in the parenchyma surrounding circumventricular regions. Evidence of associated nitration was also found. Sustained increases in ventricular volume and reduced T2 magnetic resonance relaxometry time in cortical regions were observed during the recovery period. FosB/ΔFosB activation was evident in the dorsal raphe during recovery. Persistent central inflammation and cellular activation may underpin the emergence of symptoms of depression and anxiety in experimental colitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diagnosis and staging of diabetic kidney disease (DKD) via the serial assessment of routine laboratory indices lacks the granularity required to resolve the heterogeneous disease mechanisms driving ...progression in the individual patient. A systems nephrology approach may help resolve mechanisms underlying this clinically apparent heterogeneity, paving a way for targeted treatment of DKD.
Given the limited access to kidney tissue in routine clinical care of patients with DKD, data derived from renal tissue in preclinical model systems, including animal and in vitro models, can play a central role in the development of a targeted systems-based approach to DKD. Multi-centre prospective cohort studies, including the Kidney Precision Medicine Project (KPMP) and the European Nephrectomy Biobank (ENBiBA) project, will improve access to human diabetic kidney tissue for research purposes. Integration of diverse data domains from such initiatives including clinical phenotypic data, renal and retinal imaging biomarkers, histopathological and ultrastructural data, and an array of molecular omics (transcriptomics, proteomics, etc.) alongside multi-dimensional data from preclinical modelling offers exciting opportunities to unravel individual-level mechanisms underlying progressive DKD. The application of machine and deep learning approaches may particularly enhance insights derived from imaging and histopathological/ultrastructural data domains.
Integration of data from multiple model systems (in vitro, animal models, and patients) and from diverse domains (clinical phenotypic, imaging, histopathological/ultrastructural, and molecular omics) offers potential to create a precision medicine approach to DKD care wherein the right treatments are offered to the right patients at the right time.
Surrogate measures of glomerular filtration rate (GFR) continue to serve as pivotal determinants of the incidence, severity, and management of acute kidney injury (AKI), as well as the primary ...reference point underpinning knowledge of its pathophysiology. However, several clinically important deficits in aspects of renal excretory function during AKI other than GFR decline, including acid-base regulation, electrolyte and water balance, and urinary concentrating capacity, can evade detection when diagnostic criteria are built around purely GFR-based assessments. The use of putative markers of tubular injury to detect "sub-clinical" AKI has been proposed to expand the definition and diagnostic criteria for AKI, but their diagnostic performance is curtailed by ambiguity with respect to their biological meaning and context specificity. Efforts to devise new holistic assessments of overall renal functional compromise in AKI would foster the capacity to better personalize patient care by replacing biomarker threshold-based diagnostic criteria with a shift to assessment of compromise along a pathophysiological continuum. The term AKI refers to a syndrome of sudden renal deterioration, the severity of which is classified by precise diagnostic criteria that have unquestionable utility in patient management as well as blatant limitations. Particularly, the absence of an explicit pathophysiological definition of AKI curtails further scientific development and clinical handling, entrapping the field within its present narrow GFR-based view. A refreshed approach based on a more holistic consideration of renal functional impairment in AKI as the basis for a new diagnostic concept that reaches beyond the boundaries imposed by the current GFR threshold-based classification of AKI, capturing broader aspects of pathogenesis, could enhance AKI prevention strategies and improve AKI patient outcome and prognosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. ...Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.
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BFBNIB, EMUNI, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UL, UM, UPCLJ, UPUK, VKSCE, ZAGLJ, ZRSKP
The alarming rise in obesity and relative lack of pharmacotherapies to treat, what is becoming a global epidemic, has necessitated that an increasing number of bariatric procedures be performed. ...Several surgical techniques have been developed during the last 50 years and the advent of laparoscopic surgery has increased the safety and efficacy of these procedures. Bariatric surgery is by a substantial margin, the most efficacious means of achieving sustained weight loss maintenance in patients with obesity. Roux-en-Y gastric bypass surgery (RYGB) elicits the most favourable metabolic outcomes with attendant benefits for type 2 diabetes and, cardiovascular disease as well as endocrine disorders and cancers in females. RYGB is the most extensively studied bariatric procedure regarding mechanism of action. In this review we catalogue the multiple alterations in secretion of gut hormones (ghrelin, obestatin, cholecystokinin, GLP-1, PYY, GIP, oxyntomodulin, glicentin and GLP-2) occurring after RYGB and summarise evidence indicating that these changes play a role in the reduction of food intake and improvements in glucose homeostasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND:Debate persists regarding the role of Desulfovibrio subspecies in ulcerative colitis. Combined microscopic and molecular techniques enable this issue to be investigated by allowing precise ...enumeration of specific bacterial species within the colonic mucous gel. The aim of this study was to combine laser capture microdissection and quantitative polymerase chain reaction to determine Desulfovibrio copy number in crypt-associated mucous gel in health and in acute and chronic ulcerative colitis.
METHODS:Colonic mucosal biopsies were harvested from healthy controls (n = 19) and patients with acute (n = 10) or chronic (n = 10) ulcerative colitis. Crypt-associated mucous gel was obtained by laser capture microdissection throughout the colon. Pan-bacterial 16S rRNA and Desulfovibrio copy number/mm were obtained by polymerase chain reaction at each locus. Bacterial copy numbers were interrogated for correlation with location and disease activity. Data were evaluated using a combination of ordinary linear methods and linear mixed-effects models to cater for multiple interactions.
RESULTS:Desulfovibrio positivity was significantly increased in acute and chronic ulcerative colitis at multiple levels within the colon, and after normalization with total bacterial signal, the relative Desulfovibrio load was increased in acute colitis compared with controls. Desulfovibrio counts did not significantly correlate with age, disease duration, or disease activity but interlevel correlations were found in adjacent colonic segments in the healthy control and chronic ulcerative colitis groups.
CONCLUSION:The presence of Desulfovibrio subspecies is increased in ulcerative colitis and the data presented suggest that these bacteria represent an increased percentage of the colonic microbiome in acute ulcerative colitis.
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