Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, ...emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age‐related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood–brain barrier to reach the target areas in the brain or to regulate the function of the blood–brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood–brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential.
LINKED ARTICLES
This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc
There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in ...patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience.
To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer.
We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence.
A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27–4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics FIGO I–II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57–0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07–2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63).
In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I–II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.
Context:
Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is ...unclear.
Objective:
Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance.
Design:
GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients.
Results:
GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR.
Conclusions:
GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.
Scope
The effects of triglyceride‐rich lipoproteins (TRLs) on the miRNA expression of endothelial cells, which are very involved in atherosclerosis, according to the type of diet are not known.
...Methods and Results
The differences between the effects of TRLs isolated from blood of subjects after a high‐fat meal with extra‐virgin olive oil (EVOO) and sunflower oil (SO) on the microRNA‐Seq profile related to atherosclerosis in human umbilical vein endothelial cells are analyzed. 28 upregulated microRNAs with EVOO‐derived TRLs, which can regulate 22 genes related to atherosclerosis, are found. 21 upregulated microRNAs with SO‐derived TRLs, which can regulate 20 genes related to atherosclerosis, are found. These microRNAs are mainly involved in angiogenesis, with a predominance of an anti‐angiogenic effect with EVOO‐derived TRLs. Other microRNAs upregulated with SO‐derived TRLs are involved in cardiovascular diseases. Pathways for the target genes obtained from the upregulated microRNA with EVOO‐derived TRLs are involved in lipid metabolism and inflammatory and defense response, while those with SO‐derived TRLs are involved in lipid metabolic process.
Conclusion
EVOO‐derived TRLs seem to produce a more atheroprotective profile than SO‐derived TRLs. This study provides alternative mechanisms on the protective role of EVOO against the atherogenic process through microRNA regulation in endothelial cells.
Triglyceride‐rich lipoproteins obtained after a high‐fat meal with extra‐virgin olive oil (EVOO) seem to produce a more atheroprotective miRNA profile than those obtained with sunflower oil (SO). Pathways for the target genes obtained from the upregulated miRNA with EVOO are involved in lipid metabolism and inflammatory and defense response, while those with SO are involved in lipid metabolic process.
Bariatric surgery induces changes in gut microbiota that have been suggested to contribute to weight loss and metabolic improvement. However, whether preoperative gut microbiota composition could ...predict response to bariatric surgery has not yet been elucidated.
Seventy-six patients who underwent sleeve gastrectomy were classified according to the percentage of excess weight loss (%EWL) 1 year after surgery in the responder group: >50%EWL (n=50) and the nonresponder group: <50%EWL (n=26). Patients were evaluated before surgery, and 3 months and 1 year after surgery. Gut microbiota composition was analyzed before surgery (n=76) and 3 months after bariatric surgery (n=40).
Diversity analysis did not show differences between groups before surgery or 3 months after surgery. Before surgery, there were differences in the abundance of members belonging to Bacteroidetes and Firmicutes phyla (nonresponder group: enriched in Bacteroidaceae, Bacteroides, Bacteroides uniformis, Alistipes finegoldii, Alistipes alistipes, Dorea formicigenerans, and Ruminococcus gnavus. Responder group: enriched in Peptostreptococcaceae, Gemmiger, Gemiger formicilis, Barnesiella, Prevotellaceae, and Prevotella; linear discriminant analysis >2; p < 0.05). Prevotella-to-Bacteroides ratio was significantly lower in the nonresponder group compared to the responder group (p = 0.048). After surgery, the responder group showed an enrichment in taxa that have been shown to have beneficial effects on host metabolism. Before surgery, PICRUSt analysis showed an enrichment in pathways involved in the biosynthesis components of the O-antigen polysaccharideunits in lipopolysaccharides in the nonresponder group.
Preoperative gut microbiota could have an impact on bariatric surgery outcomes. Prevotella-to-Bacteroides ratio could be used as a predictive tool for weight loss trajectory. Early after surgery, patients who experienced successful weight loss showed an enrichment in taxa related to beneficial effects on host metabolism.
The postprandial state seems to have a direct influence on oxidative status and insulin resistance. We determined the effect of an increase in plasma triglycerides after a high‐fat meal on oxidative ...stress in severely obese patients with differing degrees of insulin resistance. The study was undertaken in 60 severely obese persons who received a 60‐g fat overload with a commercial preparation. Measurements were made of insulin resistance, the plasma activity of various antioxidant enzymes, the total antioxidant capacity (TAC) and the plasma concentration of thiobarbituric acid reactive substances (TBARS). The patients with greater insulin resistance had a lower plasma superoxide dismutase (SOD) activity (P < 0.05) and a greater glutathione peroxidase (GSH‐Px) activity (P < 0.05). The high‐fat meal caused a significant reduction in SOD activity and an increase in the plasma concentration of TBARS in all the patients. Only the patients with lower insulin resistance experienced a significant increase in plasma catalase activity (2.22 ± 1.02 vs. 2.93 ± 1.22 nmol/min/ml, P < 0.01), remaining stable in the patients with greater insulin resistance. These latter patients had a reduction in plasma TAC (6.92 ± 1.93 vs. 6.29 ± 1.80 mmol/l, P < 0.01). In conclusion, our results show a close association between the degree of insulin resistance and markers of oxidative stress, both before and after a high‐fat meal. The postprandial state causes an important increase in oxidative stress, especially in severely obese persons with greater insulin resistance. However, we are unable to determine from this study whether there is first an increase in oxidative stress or in insulin resistance.
Background/aim
Alterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to ...evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy.
Subjects/methods
110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis.
Results
Gut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in
Enterobacteriaceae
(an ethanol-producing bacteria),
Acidaminococcus
and
Megasphaera
and the depletion of
Eggerthellaceae
and
Ruminococcaceae
(SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in
Enterobacteriaceae
and a decrease in
Ruminococcaceae
. Specifically,
Escherichia coli
was associated with steatosis and necroinflammatory activity, whilst
Escherichia-shigella
was associated with fibrosis and necroinflammatory activity.
Conclusions
We established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.
Context:
The relationship between 25-hydroxyvitamin D 25(OH)D and obesity and type 2 diabetes is not completely understood. Vitamin D receptor (VDR) expression in adipose tissue (AT) is related to ...obesity and might be regulated by 1,25-dihydroxyvitamin D3 1,25(OH)2D3.
Objective:
To analyze serum 25(OH)D and VDR gene expression in AT according to body mass index (BMI) and glycemic status and the effect of 1,25(OH)2D3 on AT according to BMI.
Design and Patients:
Two cohorts were studied: 1) 118 subjects classified according to their BMI (lean, overweight, obese, or morbidly obese MO) and their glycemic status (normoglycemic NG and prediabetic and diabetic P&D); and 2) 30 obese subjects (BMI > 30 kg/m2) classified as NG and P&D. VDR gene expression was analyzed during preadipocyte differentiation and in vitro stimulation with 1,25(OH)2D3 of AT explants from donors with different BMI values.
Setting:
University Hospital.
Main Outcome Measures:
Serum 25(OH)D, parathyroid hormone (PTH), and AT VDR gene expression.
Results:
25(OH)D levels were lower in P&D than NG subjects, significantly so in the lean and MO groups (P < .05). 25(OH)D levels correlated negatively with homeostasis model of assessment for insulin resistance (HOMA-IR) (r = −0.200; P = .032) and glucose (r = −0.295; P = .001), but not with BMI. VDR gene expression was higher in MO than in the other BMI groups (P < .05). 1,25(OH)2D3 increased VDR gene expression in AT from obese patients (P < .05) but not from lean subjects.
Conclusions:
25(OH)D levels are diminished in P&D compared to NG subjects, independently of BMI, and are closely related to glucose metabolism variables, suggesting that vitamin D deficiency is associated more with carbohydrate metabolism than with obesity. Moreover, AT has a different response to 1,25(OH)2D3 depending on the degree of obesity.
Metabolic surgery is the most effective therapeutic strategy for the management of type 2 diabetes (T2DM). Several preoperative clinical factors have been associated with T2DM remission after ...metabolic surgery. However, other potential predictors remain unexplored.
To assess the role of basal (pre-surgery) clinical and biochemical parameters in T2DM remission after metabolic surgery.
A prospective study including 98 patients with T2DM undergoing metabolic surgery was performed. Clinical, anthropometric, and biochemical data were collected at baseline and 1 year following metabolic surgery.
Patients without T2DM remission 1 year after metabolic surgery presented a longer duration of diabetes and higher glycated hemoglobin (HbA1c) levels; a higher percentage of these subjects were using insulin therapy, antihypertensive drugs, and lipid-lowering therapies before metabolic surgery, compared to those patients with T2DM remission. A lower percentage of T2DM remission after metabolic surgery was observed among patients with hypertension/hypercholesterolemia before surgery, compared to those patients without hypertension/hypercholesterolemia (51.7 % vs 86.8 %, p < 0.001, and 38.5 % vs 75 %, p < 0.001, respectively), and among patients with longer duration of diabetes (≥5 years vs <5 years; 44.4 % vs 83 %, respectively; p < 0.001). In the logistic regression model, diabetes duration, basal HbA1c, and the presence of hypertension and hypercholesterolemia before surgery were inversely related to T2DM remission following metabolic surgery, after adjusting for sex, age, waist circumference, and type of surgery.
In a cohort of patients with obesity and T2DM, preoperative hypertension and hypercholesterolemia, together with a longer diabetes duration and higher HbA1c concentrations, were independent predictors of T2DM persistence after metabolic surgery.
Abstract
Context
Climate change and global warming have been hypothesized to influence the increased prevalence of obesity worldwide. However, the evidence is scarce.
Objective
We aimed to ...investigate how outside temperature might affect adipose tissue physiology and metabolic traits.
Methods
The expression of genes involved in thermogenesis/browning and adipogenesis were evaluated (through quantitative polymerase chain reaction) in the subcutaneous adipose tissue (SAT) from 1083 individuals recruited in 5 different regions of Spain (3 in the North and 2 in the South). Plasma biochemical variables and adiponectin (enzyme-linked immunosorbent assay) were collected through standardized protocols. Mean environmental outdoor temperatures were obtained from the National Agency of Meteorology. Univariate, multivariate, and artificial intelligence analyses (Boruta algorithm) were performed.
Results
The SAT expression of genes associated with browning (UCP1, PRDM16, and CIDEA) and ADIPOQ were significantly and negatively associated with minimum, average, and maximum temperatures. The latter temperatures were also negatively associated with the expression of genes involved in adipogenesis (FASN, SLC2A4, and PLIN1). Decreased SAT expression of UCP1 and ADIPOQ messenger RNA and circulating adiponectin were observed with increasing temperatures in all individuals as a whole and within participants with obesity in univariate, multivariate, and artificial intelligence analyses. The differences remained statistically significant in individuals without type 2 diabetes and in samples collected during winter.
Conclusion
Decreased adipose tissue expression of genes involved in browning and adiponectin with increased environmental temperatures were observed. Given the North-South gradient of obesity prevalence in these same regions, the present observations could have implications for the relationship of the obesity pandemic with global warming.
PDF
