Function In Obesity Research Articles

The nutrition and immunity (nutrIMM) study: protocol for a non-randomized, four-arm parallel-group, controlled feeding trial investigating immune function in obesity and type 2 diabetes.

Individuals with obesity and/or type 2 diabetes are at higher risk of infection and have worse prognoses compared to healthy individuals. Several factors may influence immune responses in this population, including high adiposity, hyperglycemia, and unhealthy dietary habits. However, there is insufficient data on the independent or clustered contribution of these factors to obesity-related immune dysfunction, especially accounting for dietary intake. This study aims to establish the independent contribution of obesity and hyperglycemia to immune dysfunction independent of diet in adults with and without obesity with or without type 2 diabetes. The Nutrition and Immunity (nutrIMM) study is a single-centre, non-randomized, four-arm, parallel-group, controlled feeding trial. It will enroll adults without obesity (Lean-NG) and with obesity and three metabolic phenotypes of normoglycemia, glucose intolerance, and type 2 diabetes. Participants will be assigned to one of four groups and will consume a standard North American-type diet for 4 weeks. The primary outcomes are plasma concentration of C-reactive protein and concentration of ex-vivo interleukin-2 secreted upon stimulation of T cells with phytohemagglutinin. This will be the first controlled feeding study examining the contribution of obesity, hyperglycemia, and diet on systemic inflammation, immune cell phenotype, and function in adults of both sexes. Results of this clinical trial can ultimately be used to develop personalized dietary strategies to optimize immune function in individuals with obesity with different immune and metabolic profiles. ClinicalTrials.gov, identifier NCT04291391.

The Transcription Factor HOXA5: Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction.

The transcription factor HOXA5, from the HOX gene family, has long been studied due to its critical role in physiological activities in normal cells, such as organ development and body patterning, and pathological activities in cancer cells. Nonetheless, recent evidence supports the hypothesis of a role for HOXA5 in metabolic diseases, particularly in obesity and type 2 diabetes (T2D). In line with the current opinion that adipocyte and adipose tissue (AT) dysfunction belong to the group of primary defects in obesity, linking this condition to an increased risk of insulin resistance (IR) and T2D, the HOXA5 gene has been shown to regulate adipocyte function and AT remodeling both in humans and mice. Epigenetics adds complexity to HOXA5 gene regulation in metabolic diseases. Indeed, epigenetic mechanisms, specifically DNA methylation, influence the dynamic HOXA5 expression profile. In human AT, the DNA methylation profile at the HOXA5 gene is associated with hypertrophic obesity and an increased risk of developing T2D. Thus, an inappropriate HOXA5 gene expression may be a mechanism causing or maintaining an impaired AT function in obesity and potentially linking obesity to its associated disorders. In this review, we integrate the current evidence about the involvement of HOXA5 in regulating AT function, as well as its association with the pathogenesis of obesity and T2D. We also summarize the current knowledge on the role of DNA methylation in controlling HOXA5 expression. Moreover, considering the susceptibility of epigenetic changes to reversal through targeted interventions, we discuss the potential therapeutic value of targeting HOXA5 DNA methylation changes in the treatment of metabolic diseases.

Self-control training supplementing inpatient multidisciplinary obesity treatment in children and adolescents

Research points to self-control as a possible mechanism for facilitating health behaviour and weight loss. The dual pathway model underpins the role of strong bottom-up reactivity towards food and weak top-down executive functions in obesity. Despite flourishing lab studies on attention bias modification or inhibition trainings, relatively few focused on training both processes to improve self-control in children and adolescents in inpatient multidisciplinary obesity treatment (MOT).Being part of the WELCOME project, this study investigated the effectiveness of Brain Fitness training (using the Dot Probe and Go/No-Go) as an adjunct to inpatient MOT in 131 Belgian children and adolescents. Changes in self-control (performance-based inhibitory control and attention bias as well as self-reported eating behaviour) in the experimental group were compared to sham training. Multiple Imputation was used to handle missing data.Inhibitory control and external eating improved over time (pre/post/follow-up), but we found no evidence for a significant interaction between time and condition. Future research should pay more attention to the role of individual variability in baseline self-control, sham training, and ecological validity of self-control training to improve real-life health behaviour and treatment perspectives for children and adolescents with weight problems.

Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity.

Leptin is an adipokine secreted in proportion to adipocyte mass and is therefore increased in obesity. Leptin signaling has been shown to directly promote inflammatory T helper 1 (Th1) and T helper 17 (Th17) cell number and function. Since T cells have a critical role in driving inflammation and systemic glucose intolerance in obesity, we sought to determine the role of leptin signaling in this context. Male and female T cell-specific leptin receptor knockout mice and littermate controls were placed on low-fat diet or high-fat diet to induce obesity for 18 weeks. Weight gain, serum glucose levels, systemic glucose tolerance, T cell metabolism, and T cell differentiation and cytokine production were examined. In both male and female mice, T cell-specific leptin receptor deficiency did not reverse impaired glucose tolerance in obesity, although it did prevent impaired fasting glucose levels in obese mice compared to littermate controls, in a sex dependent manner. Despite these minimal effects on systemic metabolism, T cell-specific leptin signaling was required for changes in T cell metabolism, differentiation, and cytokine production observed in mice fed high-fat diet compared to low-fat diet. Specifically, we observed increased T cell oxidative metabolism, increased CD4+ T cell IFN-γ expression, and increased proportion of T regulatory (Treg) cells in control mice fed high-fat diet compared to low-fat diet, which were not observed in the leptin receptor conditional knockout mice, suggesting that leptin receptor signaling is required for some of the inflammatory changes observed in T cells in obesity. T cell-specific deficiency of leptin signaling alters T cell metabolism and function in obesity but has minimal effects on obesity-associated systemic metabolism. These results suggest a redundancy in cytokine receptor signaling pathways in response to inflammatory signals in obesity.

DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters.

The altered functions of adipose tissue are one of the main issues in obesity. Bariatric surgery is associated with improvement of obesity associated comorbidities. Here DNA methylation remodeling in adipose tissue after bariatric surgery is examined. After six months postoperative, DNA methylation shows changes in 1155 CpG sites, 66 of these sites correlate with body mass index. Some sites also show correlation with LDL-C, HDL-C, total cholesterol, and triglycerides. CpG sites are located in genes that have not previously been linked to obesity or metabolic diseases. GNAS complex locus is one of those that presented CpG site with the greatest changes after surgery, and the most significant correlation with BMI and lipid profiles. These results show that epigenetic regulation may be involved in the alteration of adipose tissue functions in obesity.

Thyroid Function in Obese Patients without Thyroid Disorders

Background: Thyroid status influences weight and thyroid function is altered in obese individuals. Objective: This study aimed to see the levels of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) and their relationship with the parameters of obesity in obese children and adults with primary exogenous obesity without thyroid disorders. Materials and Methods: This retrospective cross-sectional study was done in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, from May 2019 to March 2020 in 238 children and adults with primary exogenous obesity. Individuals with thyroid disorders were excluded from the study. Data were taken from hospital records to assess the thyroid function (FT4 and TSH) in obesity. Results: Two hundred and thirty-eight individuals with a mean age of 16.42 ± 9.72 years (range 3–62 years) and mean body mass index of 31.09 ± 7.64 kg/m2 were included in the study. The distribution of FT4 was normal and that of TSH was skewed to the right. Ninety-five percent confidence interval (CI) of FT4 and TSH was within the normal reference range. Ninety-five percent CI of FT4 was in the upper end of normal (1.176–1.251 mIU/L in ≤20 years and 1.094–1.306 mIU/L in >20 years) and that of TSH was in the lower end of normal (2.619–3.207 mIU/L in ≤20 years and 2.616–4.141 mIU/L in >20 years). About 13.4% had low FT4 and 15.4% had raised TSH. Waist circumference (WC) had a negative linear association with FT4 (r = −0.229, P = 0.003, R 2 = 5.24%), which was not present in the multivariate analysis. WC was significantly higher in the first versus third quartile of FT4 (103.974 ± 17.211 vs. 94.818 ± 14.544 cm). Conclusion: FT4 and TSH levels were in the lower and upper end of normal, respectively, in obese patients without thyroid disorders. Central obesity was negatively associated with FT4 in obese individuals.

TNFa-TNFRI interaction impairs endothelial calcium signaling and elevates blood pressure in obesity

Endothelial dysfunction in small arteries is a hallmark of obesity-induced hypertension. Recent studies show that the formation of peroxynitrite, a reactive nitrogen species, impairs endothelium-dependent vasodilation. It is well known that inflammatory cytokines promote the formation of cellular peroxynitrite. In this regard, tumor necrosis factor-alpha (TNFα) signaling has been proposed as a contributor to endothelial dysfunction in obesity. Notably, the vascular wall has been proposed as a source of TNFα generation in obesity, although the vascular TNFα signaling mechanisms in obesity are unclear. We hypothesized that vascular wall-derived TNFα acts locally to impair endothelial function in obesity. We previously reported that high-fat diet feeding (60% kcal fat) for 14 weeks elevates blood pressure in mice. Flow cytometry and mRNA expression studies indicated an increase in TNFα levels in freshly isolated SMCs from small mesenteric arteries (MAs) of high-fat diet-fed obese mice compared to normal chow-fed control mice. However, TNFα levels in endothelial cells (ECs) from obese mice were not different from those in ECs from control mice. Tamoxifen-inducible SMC-specific TNFα -/- (TNFα SMC -/- ) mice did not show an increase in blood pressure after high-fat diet feeding. However, tamoxifen-inducible EC-specific TNFα -/- (TNFα EC -/- ) mice showed a similar increase in blood pressure after high-fat diet feeding compared to the control mice. Both TNFα SMC -/- and TNFα EC -/- showed a similar increase in body weight after high-fat diet feeding when compared to control mice, suggesting that differences in weight gain did not contribute to lower blood pressure in obese TNFα SMC -/- mice. Together, these results indicated that SMC TNFα plays a critical role in blood pressure elevation in obesity. The pro-inflammatory effects of TNFα occur mainly through TNFα receptor-I (TNFRI) activation. Therefore, we postulated that TNFα released from SMCs acts locally on EC TNFRI. Endothelium-dependent vasodilation to acetylcholine was improved in obese TNFα SMC -/- mice compared to obese control mice. Previous studies showed that decreased Ca 2+ influx through endothelial TRPV4 (transient receptor potential vanilloid 4) channels contribute to blood pressure elevation in obese mice. The activity of TRPV4 channels is also improved in ECs from obese TNFα SMC -/- mice. Treatment with a selective TNFRI signaling inhibitor (R7050, 10 mg/kg, i.p., once a day for 14 days) reduced the blood pressure to normal levels in obese mice but did not affect blood pressure in control mice. R7050 treatment also restored endothelium-dependent dilation of MAs and the activity of TRPV4 channels in ECs. Collectively, our findings indicate that vascular TNFα impairs endothelial calcium signaling and elevates blood pressure in obesity, highlighting the role of SMCs as a source of TNFα in obesity This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exposure to a static magnetic field attenuates hepatic damage and function abnormality in obese and diabetic mice

Static magnetic fields (SMFs) exhibit significant effect on health care. However, the effect of SMF on hepatic metabolism and function in obesity and diabetes are still unknown. Liver is not only the main site for glucolipid metabolism but also the core part for iron metabolism regulation. Dysregulations of iron metabolism and redox status are risk factors for the development of hepatic injury and affect glucolipid metabolism in obesity and diabetes. Mice of HFD-induced obesity and HFD/streptozocin-induced diabetes were exposed to a moderate-intensity SMF (0.4–0.7 T, direction: upward, 4 h/day, 8 weeks). Results showed that SMF attenuated hepatic damage by decreasing inflammation and fibrosis in obese and diabetic mice. SMF had no effects on improving glucose/insulin tolerance but regulated proteins (GLUT1 and GLUT4) and genes (G6pc, Pdk4, Gys2 and Pkl) participating in glucose metabolism with phosphorylation of Akt/AMPK/GSK3β. SMF also reduced lipid droplets accumulation through decreasing Plin2 and Plin5 and regulated lipid metabolism with elevated hepatic expressions of PPARγ and C/EBPα in obese mice. In addition, SMF decreased hepatic iron deposition with lower FTH1 expression and modulated systematic iron homeostasis via BMP6-mediated regulation of hepcidin. Moreover, SMF balanced hepatic redox status with regulation on mitochondrial function and MAPKs/Nrf2/HO-1 pathway. Finally, we found that SMF activated hepatic autophagy and enhanced lipophagy by upregulating PNPLA2 expression in obese and diabetic mice. Our results demonstrated that SMF significantly ameliorated the development of hepatic injury in obese and diabetic mice by inhibiting inflammatory level, improving glycolipid metabolism, regulating iron metabolism, balancing redox level and activating autophagy.

LncRNA SNHG14/miR-497a-5p/BACE1 axis modulates obesity-induced adipocyte inflammation and endoplasmic reticulum stress.

Obesity is a metabolic disease with excess weight. LncRNA SNHG14 is abnormally expressed in numerous diseases. This research aimed to enucleate the lncRNA SNHG14 role in obesity. Adipocytes were treated with free fatty acid (FFA) to establish an in vitro model for obesity. Mice were fed a high-fat diet to construct an in vivo model. Gene levels were determined using quantitative real-time PCR (RT-PCR).The protein level was checked by western blot. The lncRNA SNHG14 role in obesity was assessed using western blot and enzyme-linked immunosorbent assay. The mechanism was estimated by Starbase, dual-luciferase reporter gene assay, and RNA pull-down. LncRNA SNHG14 function in obesity was estimated using mouse xenograft models, RT-PCR, western blot, and enzyme-linked immunosorbent assay. LncRNA SNHG14 and BACE1 levels were increased, but the miR-497a-5p level was decreased in FFA-induced adipocytes. Interference with lncRNA SNHG14 reduced endoplasmic reticulum (ER) stress-related molecules GRP78 and CHOP expressions in FFA-induced adipocytes, and decreased IL-1β, IL-6, and TNF-α expressions, indicating that lncRNA SNHG14 knockdown mitigated FFA-induced ER stress and inflammation in adipocytes. Mechanistically, lncRNA SNHG14 combined with miR-497a-5p, and miR-497a-5p targeted BACE1. Meanwhile, lncRNA SNHG14 knockdown reduced levels of GRP78, CHOP, IL-1β, IL-6, and TNF-α, while cotransfection with anti-miR-497a-5p or pcDNA-BACE1 abolished these trends. Rescue assays illustrated that lncRNA SNHG14 knockdown relieved FFA-induced adipocyte ER stress and inflammation through miR-497a-5p/BACE1. Meanwhile, lncRNA SNHG14 knockdown restrained adipose inflammation and ER stress caused by obesity in vivo. LncRNA SNHG14 mediated obesity-induced adipose inflammation and ER stress through miR-497a-5p/BACE1.

Integrated transcriptomics contrasts fatty acid metabolism with hypoxia response in β-cell subpopulations associated with glycemic control

BackgroundUnderstanding how heterogeneous β-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture.ResultsWe integrate pancreatic islet single-cell and bulk RNA sequencing data to identify β-cell subpopulations based on gene expression and characterize genetic networks associated with β-cell function in obese SM/J mice. We identify β-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated with normoglycemic-obesity.ConclusionsBy integrating single-cell and bulk islet transcriptomes, our study explores β-cell heterogeneity and identifies novel subpopulations and genetic pathways associated with β-cell function in obesity.

Obesity and inflammation influence pharmacokinetic profiles of PEG-based nanoparticles.

Most patients that will be treated with soft nanoparticles (NPs) will be obese. Yet, NP testing, which begins with pharmacokinetic (PK) and toxicity studies, is carried out almost exclusively in lean rodents having healthy livers and low inflammation. To address this knowledge gap, we determined the PK and toxicity of tail-vein-injected, PEG-based cylindrical nanoparticles (CNPs) and PEGylated liposomes (PLs) as a function of obesity, liver health, and inflammation in leptin-deficient ob/ob and wild-type C57BL/6J mice. CNPs localized faster to obese livers than to healthy livers within 24h of injection. PLs localized faster to obese livers than to healthy livers but only 30min post-injection. Afterwards PL localization to lean livers was higher than localization to obese livers. Overall, PL liver signal peaked ∼6h post-injection in lean mice, ∼24h post-injection in heavy mice, and∼48h post-injection in obese mice. CNPs and PLs were non-toxic to mouse livers as assessed by histology; they reduced many cytokine and chemokine levels that were elevated by obesity. Liver macrophage depletion reduced CNP and PL liver localization as expected; liver sinusoidal endothelial cell (LSEC) depletion reduced PL liver localization but surprisingly increased CNP liver localization. The intensity of RAW264.7 macrophages was higher after CNP incubations than with PL incubations; conversely, the intensity of LSECs was higher after PL incubations than with CNP incubations. This shows the potential for key differences in NP-liver interactions. Triggering inflammation by administering lipopolysaccharide (LPS) to mice increased CNP liver localization but decreased PL liver localization. The results show that obesity and inflammation in a mouse model and in vitro affect soft PEG-based NP interaction with macrophages and LSECs, but also that these NPs can reduce pro-inflammatory pathways increased by obesity.

Sitagliptin Ameliorates Creb5/lncRNA ENSMUST00000213271-Mediated Vascular Endothelial Dysfunction in Obese Mice.

Obesity is mediated by the changes in dyslipidemia, oxidative stress, and inflammation, leading to vascular endothelial dysfunction. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 inhibitors prevent the development of endothelial dysfunction. However, the underlying mechanism still remains largely unclear. Long non-coding RNAs (lncRNAs), one class of non-coding small RNAs, have been shown to exert a regulatory impact on the endothelial function in obesity. This study aimed to investigate whether the elevation of GLP-1 by a DPP-4 inhibitor sitagliptin improved vascular endothelial function by modulating lncRNAs in obese mice and to clarify the underlying molecular mechanism. Male C57BL/6J mice were fed a high-fat diet for 4 months to induce obesity and some obese mice were treated with sitagliptin for the last 1 month. Levels of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucagon-like peptide-1 (GLP-1) in plasma were detected by ELISA. LncRNA expression profile was analyzed via microarray. Aortic relaxations were examined by myograph. Protein expressions and phosphorylations were determined using western blot. The differentially expressed lncRNAs were validated using qRT-PCR. Obese mice exhibited increased levels of TC and LDL, decreased concentrations of HDL and GLP-1 in plasma, and impaired aortic endothelium-dependent relaxations; such effects could be reversed by sitagliptin. Moreover, the altered expression profile of lncRNAs in the obese mouse aortae could be modulated by sitagliptin. Consistent with microarray analysis, qRT-PCR also revealed that lncRNA ENSMUST00000213271 was up-regulated in obese mouse aortae and aortic endothelial cells (ECs), which could be down-regulated by sitagliptin. Creb5 silencing reduced lncRNA ENSMUST00000213271 in obese mouse ECs. Knockdown of either Creb5 or lncRNA ENSMUST00000213271 restored the activation of AMPK/eNOS in obese mouse ECs. Furthermore, sitagliptin also suppressed Creb5 and lncRNA ENSMUST00000213271 and increased the phosphorylations of AMPK and eNOS in obese mice. Creb5/lncRNA ENSMUST00000213271 mediated vascular endothelial dysfunction through inhibiting AMPK/eNOS cascade in obesity. Elevation of GLP-1 by sitagliptin possibly improved endothelial function by suppressing Creb5/lncRNA ENSMUST00000213271 and subsequently restoring AMPK/eNOS activation in obese mice. This study will provide new evidence for the benefits of GLP-1 against vasculopathy in obesity.

Adipose-specific deletion of the cation channel TRPM7 inhibits TAK1 kinase-dependent inflammation and obesity in male mice

Chronic inflammation of white adipose tissue is a key link between obesity and the associated metabolic syndrome. Transient receptor potential melastatin-like 7 (TRPM7) is known to be related to inflammation; however, the role of TRPM7 in adipocyte phenotype and function in obesity remains unclear. Here, we observe that the activation of adipocyte TRPM7 plays an essential role in pro-inflammatory responses. Adult male mice are used in our experiments. Adipocyte-specific deficiency in TRPM7 attenuates the pro-inflammatory phenotype, improves glucose homeostasis, and suppresses weight gain in mice fed a high-fat diet. Mechanistically, the pro-inflammatory effect of TRPM7 is dependent on Ca2+ signaling. Ca2+ influx initiated by TRPM7 enhances transforming growth factor-β activated kinase 1 activation via the co-regulation of calcium/calmodulin-dependent protein kinase II and tumor necrosis factor receptor-associated factor 6, leading to exacerbated nuclear factor kappa B signaling. Additionally, obese mice treated with TRPM7 inhibitor are protected against obesity and insulin resistance. Our results demonstrate TRPM7 as a factor in the development of adipose inflammation that regulates insulin sensitivity in obesity.

Correlation of HbA1c and Insulin Resistance with Urine Albumin Excretion in Non Diabetic Obese Population: A Cross-sectional Study

Introduction: A number of metabolic disorders are linked to obesity, which is a global health concern. Although renal impairment is a serious side-effect of obesity, its connection to insulin resistance is still a subject of discussion. Aim: To assess the correlation between microalbuminuria and HbA1c levels, as well as the association between Insulin Resistance (IR) and renal function in obese individuals. Materials and Methods: The present study was a crosssectional study conducted in patients attending the obesity clinic, in Endocrinology department, of a tertiary hospital in Kerala, India. A total of 144 obese individuals participated, meeting age, Body Mass Index (BMI), and health-related. Insulin resistance was measured using Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while renal function was measured using the Urine Albumin Creatinine Ratio (UACR). Correlation analysis was conducted to investigate relationships between variables. Results: The study found a weak association between UACR and HbA1c levels and insulin resistance (r-value=0.159, p-value=0.056). Subjects with insulin resistance had significantly higher levels of microalbuminuria. Despite these connections, the mean UACR levels remained within the typical reference range. Conclusion: This study emphasises the importance of early renal health screening in obese individuals, with HbA1c and microalbuminuria measurements as promising methods for preventing kidney impairment. To establish causation in the complex interplay between metabolic variables and renal function in obesity and insulin resistance, future research should focus on understanding the underlying mechanisms and conducting longitudinal examinations.

Type 2 diabetes mellitus and obesity impact AD‐related pathology through overlapping and independent pathways

AbstractBackgroundIt is proposed that neuronal damage in diabetes is related to hyperglycaemia and insulin resistance, whilst inflammation and subsequent oxidative stress affects cognitive function in obesity. We investigated whether obesity and diabetes present distinct neuropathological features of neurodegeneration.MethodsTo compare amyloid, tau and cerebral glucose metabolism, we processed 1973 available PET scans for 18F‐AV‐45, 18F‐flortaucipir and 18F‐fludeoxyglucose (FDG) from 971 participants with diabetes (n=194), obesity (n=377) and without diabetes or obesity (n=400) from the Alzheimer’s Disease Neuroimaging Initiative dataset. Independent t‐tests and multivariate analysis were used for regions of interest (ROIs) analysis in participant groups with diabetes vs non‐diabetic/non‐obese and obesity vs non‐diabetic/non‐obese. This was conducted across different cognitive subgroups, namely Alzheimer’s disease, mild cognitive impairment or normal cognition. Amyloid positive and negative subjects were evaluated separately. Voxel‐wise analysis using SPM was also conducted for these groups.ResultsFor diabetes, higher amyloid uptake was found in the medial temporal regions in the cognitively normal diabetic group compared to the cognitively normal (non‐diabetic/non‐obese) group. This was also found in the amyloid positive mild cognitively impaired diabetic groups compared to mild cognitively impaired (non‐diabetic/non‐obese) group. Similarly, higher amyloid deposition was seen in the hippocampus of the cognitively normal obese group compared to the cognitively normal (non‐diabetic/non‐obese) group.Additionally, higher tau uptake was found in the whole brain (global brain value), frontal, parietal and occipital lobes for cognitively normal diabetic and obese groups, compared to cognitively normal (non‐diabetic/non‐obese) groups. Higher tau was further found in the temporal lobe and anterior cingulate of AD obesity participants compared to the AD (non‐diabetic/non‐obese) participants.Discrete cerebral glucose metabolic patterns were found in diabetes and obesity. In the diabetic groups, reduced FDG uptake was found in mild cognitively impaired participants (whole brain, frontal, parietal and occipital lobes) and amyloid positive AD participants (occipital lobe) compared to non‐diabetic/non‐obese participants. In contrast, increased FDG uptake was mainly found in amyloid negative obese participants.ConclusionsGlucose hypometabolism in diabetic participants in contrast to hypermetabolism in obese participants implies that different pathological processes of neurodegeneration occur in these two conditions. This suggests that these two conditions require different therapeutic strategies to prevent neurodegeneration.

Macrophage mitochondrial levels of iron affect adipose tissue function in obesity.

Macrophage mitochondrial levels of iron affect adipose tissue function in obesity.

Decreased left atrial function in obesity patients without known cardiovascular disease

Obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF). We hypothesized that assessment of left atrial (LA) strain may be useful to reveal precursors of HFpEF in obesity patients. Echocardiograms of obesity patients without known cardiovascular disease who underwent bariatric surgery, and echocardiograms of age- and gender matched controls were analyzed. The echocardiogram was repeated 1 year after bariatric surgery. LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured. 77 Obesity patients were compared with 46 non-obese controls. Obesity patients showed a significantly decreased LA function compared with non-obese individuals (LASr 32.2% ± 8.8% vs. 39.6% ± 10.8%, p < 0.001; LAScd 20.1% ± 7.5% vs. 24.9% ± 8.3%, p = 0.001; LASct 12.1% ± 3.6% vs. 14.5% ± 5.5%, p = 0.005). There was no difference in prevalence of diastolic dysfunction between the obesity group and controls (9.1% vs. 2.2%, p = 0.139). One year after bariatric surgery, LASr improved (32.1% ± 8.9% vs. 34.2% ± 8.7%, p = 0.048). In the multivariable linear regression analysis, BMI was associated with LASr, LAScd, and LASct (β = − 0.34, CI − 0.54 to − 0.13; β = − 0.22, CI − 0.38 to − 0.06; β = − 0.10, CI − 0.20 to − 0.004). Obesity patients without known cardiovascular disease have impairment in all phases of LA function. LA dysfunction in obesity may be an early sign of cardiac disease and may be a predictor for developing HFpEF. LASr improved 1 year after bariatric surgery, indicating potential reversibility of LA function in obesity.

Brain Mechanisms Associated With Weight Loss, Top-Down Processes A Review Study For Targeting Executive Function In Obesity And Overweight

The purpose of present study was to clarify the links between Executive function and weight-loss. We firstly investigated definition and functions of executive functions and secondly showed studies done in the links. Studies have shown that executive functions can influence on thinking and behaviors, especially, health behaviors. As a result of the preliminary search, the final keywords utilized for the investigation were weight loss, executive functions, obesity and overweight. After that, we found twelve articles and reviewed methods and results of those. The results consisted of three main methods included correlational, experimental methods and ex-post facto studies. In conclusion, present study indicated that executive control as a central control of behavior plays a key role in weight-loss.

In vitro effects of vitamins C and E on adipocyte function and redox status in obesity

BackgroundObesity is associated with a chronic inflammatory state and evident oxidative stress. Antioxidant supplementation may have beneficial effects on adipocyte function and on oxidative stress. Therefore, in this study, we investigated the in vitro effects of vitamins C, E on redox and metabolic parameters in adipocytes of control and obese Wistar rats. MethodsAdipocytes were isolated from abdominal adipose tissue and were cultured in RPMI medium for 24 h, in the presence or the absence of vitamins (C, E at 50 µM). Glucose consumption, lactate and glycerol release, ATP and triglyceride contents, redox balance were investigated with biochemical methods. ResultsThe results showed altered glucose consumption and lactate and glycerol efflux, high triglycerides, low ATP contents (P < 0.01), associated to an intracellular oxidative stress in adipocytes of obese rats. Vitamins C and E restored adipocyte function in obesity. Vitamin E increased lipolysis in adipocytes during obesity (P < 0.01). Redox balance was also modulated by antioxidants, including a reduction in intracellular hydroperoxides and carbonyl proteins levels and an increase in catalase and SOD activities and glutathione contents in adipocytes of obese rats. ConclusionTreatments with vitamins had beneficial effects on adipocyte function, and should be considered in therapeutic approaches for normalizing adipose function in obesity.

Obesity as a modifier of the cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes

AimsTo assess the association between the use of sodium-glucose cotransporter-2 (SGLT2i) and cardiovascular outcomes and death as a function of obesity among patients with type 2 diabetes. MethodsThis new-user, active-comparator cohort study used U.K.’s Clinical Practice Research Datalink linked to Hospital Episodes Statistics repository and Office for National Statistics. The cohort included 34,128 new-users of SGLT2i matched 1:1 to 34,128 new-users of dipeptidyl peptidase-4 inhibitors (DPP-4i) on body mass index and propensity score. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of major adverse cardiovascular events (MACE), overall and in body mass index (BMI) categories (≤24.9 kg/m2, 25.0–29.9 kg/m2, 30.0–39.9 kg/m2, ≥40 kg/m2). Secondary outcomes included all-cause mortality and hospitalization for heart failure. ResultsSGLT2i were associated with a decreased risk of MACE (HR: 0.78, 95 %CI: 0.69–0.88) compared to DPP-4i. This decreased risk was most pronounced among obese and severely obese patients (HR: 0.77, 95 %CI: 0.66–0.91; HR: 0.67, 95% CI: 0.49–0.91, respectively) but not among overweight patients (HR: 0.94, 95 %CI: 0.73–1.22). Similar patterns were observed for cardiovascular mortality, all-cause mortality, and heart failure. ConclusionCompared with DPP-4i, the cardioprotective effect associated with SGLT2i is stronger among patients with higher BMI.