Association between gamma glutamyl transpeptidase to HDL-Cholesterol (GGT/HDL-C) ratio and metabolic syndrome resolution after sleeve gastrectomy.

OBJECTIVE: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). METHODS: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. RESULTS: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 - 1.5], and 83.9% of patients experienced resolution of MetS. Furthermore, both the middle tertile of GGT/HDL-C (aRR: 1.28; 95% CI: 1.04 - 1.58; p = .019) and the lowest tertile (aRR: 1.27; 95% CI: 1.01 - 1.60; p = .038) showed a significant association with the resolution of MetS. CONCLUSION: Eight out of 10 patients undergoing SG experience resolution of MetS within 6 months after surgery. Patients in the middle and lower tertiles of the GGT/HDL-C were more likely to achieve this outcome. Therefore, the GGT/HDL-C ratio should be considered a valuable and efficient biomarker for preoperative assessment of bariatric surgery candidates.

Positive association between blood ethylene oxide levels and metabolic syndrome: NHANES 2013-2020.

Purpose: The exposure of Ethylene oxide (EO) is linked to systemic inflammatory response and various cardiovascular risk factors. Hemoglobin's binding to ethylene oxide (HbEO) was used to measure serum EO level. This research aims to explore the association between metabolic syndrome (MetS) and HbEO, and between HbEO and components of metabolic syndrome. Method: This research included 1842 participants from 2013 to 2020 in National Health and Nutrition Examination Survey (NHANES) database. Weighted logistic regression models were used to analyze the relationship between HbEO and metabolic syndrome risk, using odds ratio (OR) and 95% confidence interval (CI). The restricted cubic spline plot explores whether there is a dose-response relationship between HbEO and MetS risk. Subgroup analysis was performed to analyze study heterogeneity. Results: Significant differences were found in gender, educational level, marital status, diabetes status and hypertension among different groups (P < 0.001, P = 0.007, P = 0.003, P < 0.001, P < 0.001, respectively). The serum HbEO level exhibited positive correlation with metabolic syndrome risk in Q2 level (OR=1.64, 1.04~2.48), Q3 level (OR=1.99, 1.29~3.08), and Q4 level (OR=2.89, 1.92~4.34). The dose-response association suggested a possible linear association between serum HbEO and metabolic syndrome risk (P-overall=0.0359, P-non-linear=0.179). L-shaped association was found between HbEO and the risk of MetS in female population, obese population and mid-age and elder population (P-overall<0.001, P-non-linear=0.0024; P-overall=0.0107, P-non-linear=0.0055 P-overall<0.001 P-non-linear=0.0157). Conclusion: This study indicates a linear correlation between MetS and HbEO, with MetS risk escalating as HbEO levels increase. The prevalence of MetS varies depending on BMI, age and gender, and these factors can also influence MetS prevalence when exposed to EO.

Associations of sex hormone ratios with metabolic syndrome and inflammation in US adult men and women.

Background: Sex hormones play a critical role in sex differences and cardiovascular disease risk associated with metabolic syndrome (MS) and inflammation. However, the associations of sex hormone ratios with metabolic and inflammatory markers are unclear according to sex and age differences. We evaluated the associations of sex hormone ratios with MS and inflammation among males and females. Methods: A retrospective cross-sectional study was conducted by including all adults from the National Health and Nutrition Examination Survey cycles 2013-2016 and excluding any pregnant women, heart disease, diabetes, and those currently taking insulin. MS was defined using the National Cholesterol Education Program criteria and a high-sensitivity C-reactive protein (CRP) level>3 mg/L was defined as a high CRP. Measures of MS components and CRP concentrations were also analyzed. The primary exposures were testosterone to estradiol (excess androgen index), testosterone to sex hormone-binding globulin (free androgen index), and estradiol to sex hormone-binding globulin (free estradiol index). The adjusted associations were summarized with a relative risk (RR) and 95% confidence interval (CI). Results: This study included 9167 subjects with 4360 males and 4807 females. Increases in free estradiol index were positively associated with MS (RR=1.48; 95%CI: 1.39, 1.58; RR=1.31; 95%CI: 1.22, 1.40) and high CRP (RR=1.49; 95%CI: 1.25, 1.77; RR=1.26; 95%CI: 1.06, 1.50) in men with age<50 years and age≥50 years, respectively. Similarly, higher free estradiol index was also robustly associated with increased prevalence of MS (RR=1.22; 95%CI: 1.15, 1.28) and high CRP (RR=1.68; 95%CI: 1.48, 1.90) in women with age ≥50 years. Among women with age<50 years, a higher free androgen index was associated with MS (RR=1.34; 95%CI: 1.25, 1.42) and high CRP (RR=1.13; 95%CI: 1.02, 1.25). These associations were unchanged even after adjusting for all sex hormones. Conclusion: Free estradiol index was consistently and positively associated with MS and high CRP in males of all ages and older females. Free androgen index was positively associated with MS and high CRP in females with age<50 years.

Elevated serum levels of leukocyte cell-derived chemotaxin 2 are associated with the prevalence of metabolic syndrome.

AIMS: Inflammation is central to the pathogenesis of metabolic syndrome (MetS). Leukocyte cell-derived chemotaxin 2 (LECT2) is constitutively secreted in response to inflammatory stimuli and oxidative stress contributing to tissue or systemic inflammation. We explored the relationship between LECT2 levels and MetS severity in humans and mice. METHODS: Serum LECT2 levels were measured in 210 participants with MetS and 114 without MetS (non-MetS). LECT2 expression in the liver and adipose tissue was also examined in mice fed a high-fat diet (HFD) and genetically obese (ob/ob) mice. RESULTS: Serum LECT2 levels were significantly higher in MetS participants than in non-MetS participants (7.47[3.36-17.14] vs. 3.74[2.61-5.82], P < 0.001). Particularly, serum LECT2 levels were significantly elevated in participants with hypertension, central obesity, diabetes mellitus (DM), hyperglycaemia, elevated triglyceride (TG) levels, and reduced high-density lipoprotein cholesterol (HDL-C) levels compared to those in participants without these conditions. Pearson's correlation analysis showed that serum LECT2 levels were positively associated with conventional risk factors in all patients. Moreover, LECT2 was positively associated with the number of MetS components (r = 0.355, P < 0.001), indicating that higher serum LECT2 levels reflected MetS severity. Multivariate regression analysis revealed that a one standard deviation increase in LECT2 was associated with an odds ratio of 1.52 (1.01-2.29, P = 0.044) for MetS prevalence after adjusting for age, sex, body mass index, waist circumference, smoking status, white blood cell count, fasting blood glucose, TG, total cholesterol, HDL-C, blood urea nitrogen, and alanine aminotransferase. Receiver operating characteristic curve analysis confirmed the strong predictive ability of serum LECT2 levels for MetS. The optimum serum LECT2 cut-off value was 9.05. The area under the curve was 0.73 (95% confidence interval 0.68-0.78, P < 0.001), with a sensitivity and specificity of 45.71% and 95.61%, respectively. Additionally, LECT2 expression levels were higher at baseline and dramatically enhanced in metabolic organs (e.g. the liver) and adipose tissue in HFD-induced obese mice and ob/ob mice. CONCLUSIONS: Increased LECT2 levels were significantly and independently associated with the presence and severity of MetS, indicating that LECT2 could be used as a novel biomarker and clinical predictor of MetS.

Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio is a more powerful marker than TyG index for predicting metabolic syndrome in patients with type 2 diabetes mellitus.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing globally and has become a global and national public health problem that cannot be ignored as an independent predictor of cardiovascular events, cancer and all-cause mortality. γ-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) are associated with insulin resistance, dyslipidemia and oxidative stress. This study was designed to explore the relationship and predictive performance between γ-glutamyl transferase high-density lipoprotein cholesterol ratio (GGT/HDL-C) and MetS. Methods: This was a cross-sectional study. MetS was diagnosed from biochemical and anthropometric data in subjects with T2DM. Multivariate logistic regression was used to analyses the relationship between GGT/HDL-C ratio, TyG index and HOMA-IR and MetS in subjects with T2DM. Receiver operating characteristic (ROC) curve was drawn and the areas under the curve (AUC) were used to assess the ability of these indexes in screening MetS in subjects with T2DM. Statistical differences between the AUC values of these indexes were compared. In addition, we performed subgroup analyses and interactions. Results: 769 (70.55%) patients with T2DM were defined as having MetS. patients with MetS had higher anthropometric values and biochemical indicators compared to those without MetS. Multivariate logistic regression analysis of GGT/HDL-C ratio was an independent risk factor for MetS (Per 1 SD increase, OR = 2.49, 95% CI: 1.51, 4.10). According to ROC curve analysis, the value of GGT/HDL-C ratio in predicting MetS in subjects with T2DM was superior to that of TyG index and HOMA-IR. The best cut-off value for GGT/HDL-C prediction was 19.94. Conclusions: GGT/HDL-C ratio may be an important predictor of MetS in subjects with T2DM, and its predictive power is stronger than that of TyG index and HOMA-IR. The risk of MetS in subjects with T2DM is increased in the presence of a higher GGT/HDL-C ratio.

Dietary choline and betaine intake, cardio-metabolic risk factors and prevalence of metabolic syndrome among overweight and obese adults.

BACKGROUND: Choline is an important metabolite involved in phospholipids synthesis, including serum lipids, and is the immediate precursor of betaine. There are numerous studies with inconsistent results that evaluated the association between dietary choline intakes with cardiovascular risk factors. In addition, the association between dietary betaine and choline intakes with cardio-metabolic risk factors is not well studied. In the current study, our aim was to evaluate dietary choline and betaine intakes in the usual diet of obese individuals and to assess its association with serum lipids, blood pressure and glycemic markers among obese individuals. METHODS: We recruited a total number of 359 obese people aged between 20 and 50 years in the present study. A semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment; dietary choline and betaine intakes were calculated using the United States Department of Agriculture (USDA) database. National cholesterol education program adult treatment panel (NCEP-ATP)-III criteria was used metabolic syndrome (MetS) definition. Enzymatic methods were used to assess biochemical variables. Body composition was measured with the bioelectrical impedance analysis (BIA) method. RESULTS: Higher body mass index (BMI), waist to hip ratio (WHR), fat-free mass (FFM) and basal metabolic rate (BMR) were observed in higher tertiles of dietary choline intake (P < 0.01). There was no significant difference in terms of biochemical parameters among different tertiles of dietary choline intake, while systolic blood pressure (SBP) and diastolic blood pressure (DBP) were reduced in higher betaine tertiles (P < 0.05). For total dietary choline and betaine intakes, there was a reduction in DBP and low density lipoprotein (LDL) concentrations (P < 0.05). Also, a non-significant reduction in serum total cholesterol (TC), triglyceride (TG) and MetS prevalence was observed in higher tertiles of dietary choline and betaine intakes. After classification of the study population according to MetS status, there was no significant difference in biochemical variables in subjects with MetS (P > 0.05), while in the non-MetS group, SBP, DBP, TG and insulin levels reduced in higher tertiles of dietary betaine and choline (P > 0.05). CONCLUSION: According to our findings, higher dietary intakes of choline and betaine were associated with lower levels of blood pressure and LDL concentrations among obese individuals. Further studies are warranted to confirm the results of the current study.

Circulating Lipocalin-2 level is positively associated with cognitive impairment in patients with metabolic syndrome.

The association between Lipocalin-2 (LCN2) and cognition in patients with metabolic syndrome (MetS) has not been thoroughly investigated. We aimed to evaluate whether serum LCN2 levels are associated with the alteration of cognitive function in patients with MetS. The total of 191 non-demented participants with MetS were enrolled onto the study in 2015, and a cohort study was conducted in a subpopulation in 2020. After adjustment for sex, age, waist circumference, creatinine levels, and HbA1C, an association between the higher serum LCN2 levels and the lower Montreal cognitive assessment (MoCA) scores was observed (B = - 0.045; 95%CI - 0.087, - 0.004; p 0.030). A total of 30 participants were followed-up in 2020. Serum LCN2 levels were decreased in correlation with age (23.31 ± 12.32 ng/ml in 2015 and 15.98 ± 11.28 ng/ml in 2020, p 0.024), while other metabolic parameters were unchanged. Magnetic resonance imaging studies were conducted on a subsample of patients in 2020 (n = 15). Associations between high serum LCN2 levels from 2015 and 2020 and changes in brain volume of hippocampus and prefrontal cortex from 2020 have been observed. These findings suggest a relationship between changes of the level of circulating LCN2, cognitive impairment, and changes in brain volume in patients with MetS. However, further investigation is still needed to explore the direct effect of circulating LCN2 on the cognition of MetS patients.

No association of natural killer cell number and function in peripheral blood with overweight/obesity and metabolic syndrome in a cohort of young women.

AIM: To reexamine the associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome in a large, well-phenotyped human cohort. METHODS: Cross-sectional analysis of 273 women in the PPSDiab Study; measurement of absolute and relative number of NK cells in peripheral blood, and of functional parameters CD69 positivity and cytotoxicity against K562 cells; group comparison of NK cell characteristics between lean, overweight, and obese participants, as well as metabolic syndrome scores of 0, 1, 2, and ≥3; Spearman correlation analyses to clinical parameters related to the metabolic syndrome. RESULTS: We found no differences in NK cell number and function between lean, overweight, and obese women (relative NK cell number (median (Q1-Q3), [%]) 5.1(2.6-9.4) vs. 4.8 (2.9-8.4) vs. 3.8 (1.7-7.8), p = 0.187; absolute NK cell number [106 /L]: 86.9 (44.6-188.8) vs. 92.6 (52.5-154.6) vs. 85.9 (44-153.8), p = 0.632; CD69+ [%]: 27.2 (12.9-44.3) vs. 37.6 (13.2-52.8) vs. 33.6 (16.3-45), p = 0.136; cytotoxicity [%]: 11.0 (7.1-14.5) vs. 8.5 (6.4-13.2) vs. 11.3 (8.7-14.2), p = 0.094), as well as between different metabolic syndrome scores. Nonesterified fatty acids correlated with absolute and relative NK cell number and cytotoxicity (ρ [p-value]: 0.142 [0.021], 0.119 [0.049], and 0.131 [0.035], respectively). Relative NK cell number further correlated with high-density lipoprotein cholesterol (0.144 [0.018]) and cytotoxicity with 2 h glucose in oral glucose tolerance testing (0.132 [0.034]). CD69 positivity correlated with body fat (0.141 [0.021]), triglycerides (0.129 [0.033]), and plasma leptin (0.155 [0.010]). After correction for multiple testing, none of the associations remained significant. CONCLUSION: In the present study, we observed no associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome. Extreme phenotypes of obesity and the metabolic syndrome might have caused differing results in previous studies. Further analyses with a focus on compartments other than peripheral blood may help to clarify the relation between NK cells and metabolic diseases.

Low-grade inflammation in survivors of childhood cancer and testicular cancer and its association with hypogonadism and metabolic risk factors.

BACKGROUND: In childhood (CCS) and testicular cancer (TCS) survivors, low-grade inflammation may represent a link between testosterone deficiency (hypogonadism) and risk of metabolic syndrome. We aimed to study levels of inflammatory markers in CCS and TCS and the association with hypogonadism and future cardio-metabolic risk factors. METHODS: Serum levels of inflammatory markers and testosterone were analyzed in CCS (n = 90), and TCS (n = 64, median time from diagnosis: 20 and 2.0 years, respectively), and in controls (n = 44). Differences in levels between patients and controls were calculated using univariate analysis of variance. T-test and logistic regression were applied to compare levels of cardio-metabolic risk factors and odds ratio (OR) of hypogonadism and metabolic syndrome in low and high inflammatory marker groups after 4-12 years of follow up. Adjustment for age, smoking, and active cancer was made. RESULTS: TCS and CCS, as compared to controls, had 1.44 (95%CI 1.06-1.96) and 1.25 (95 CI 1.02-1.53) times higher levels of IL-8, respectively. High IL-6 levels were associated with hypogonadism at baseline (OR 2.83, 95%CI 1.25-6.43) and the association was stronger for high IL-6 combined with low IL-10 levels (OR 3.10, 95%CI 1.37-7.01). High IL-6 levels were also associated with higher BMI, waist circumference, insulin, and HbA1c at follow up. High TNF-α was associated with higher diastolic blood pressure. No individual inflammatory marker was significantly associated with risk of metabolic syndrome at follow up. High IL-6 combined with low IL-10 levels were associated with risk of metabolic syndrome (OR 3.83, 95%CI 1.07-13.75), however not statistically significantly after adjustment. CONCLUSION: TCS and CCS present with low-grade inflammation. High IL-6 levels were associated with hypogonadism and cardio-metabolic risk factors. Low IL-10 levels might reinforce the IL-6 mediated risk of developing metabolic syndrome.

Prolactin Response to Metformin in Cabergoline-Resistant Prolactinomas: A Pilot Study.

INTRODUCTION: Cabergoline is the treatment of choice for prolactinomas. However, 10-20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. SUBJECTS AND METHODS: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26-61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38-386 ng/mL) under cabergoline treatment (2-7 mg/week) for at least 6 months (6-108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0-2.5 g v.o./day) was given according to patients' tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30-60 days) and long-term (120-180 days) metformin treatment. RESULTS: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30-60 days, and at 120-180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0-2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. CONCLUSION: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.

Association of Serum Galectin-3-Binding Protein and Metabolic Syndrome in a Chinese Adult Population.

Background: Galectin-3-binding protein (GAL-3BP) is a ubiquitous and multifunctional secreted glycoprotein, which functions in innate immunity and has been highlighted as a potential mediator of adipose inflammation in obesity. In this study, we aimed to identify whether GAL-3BP is a novel biological marker for metabolic syndrome (MetS). Methods: The biochemical and anthropometric variables of the 570 participants in this study were evaluated using standard procedures. Their serum GAL-3BP levels were measured using enzyme-linked immunosorbent assay (ELISA), while the association between the glycoprotein and MetS was analyzed using multiple logistic regression analyses. Moreover, an experimental MetS model was established. The expression of GAL-3BP in serum and adipose tissue was measured using ELISA and western blotting. Lipid accumulation was determined with the use of immunohistochemistry and immunofluorescent staining. Results: The serum GAL-3BP level was found to be positively associated with MetS. The logistic regression analyses demonstrated that participants expressing the upper levels of GAL-3BP were more likely to develop MetS than those expressing less of the glycoprotein (OR = 2.39, 95%CI: 1.49, 3.83). The association between the serum GAL-3BP level and MetS was found preferentially in postmenopausal women (OR = 2.30, 95%CI: 1.31, 4.05). In addition, GAL-3BP was increased in the serum and visceral adipose tissue (VAT) of high fat diet (HFD) mice. Moreover, GAL-3BP was highly expressed in VAT macrophages. Conclusions: This study confirmed serum GAL-3BP to be positively associated with MetS, highlighting it as a useful biological marker of MetS in Chinese participants.

The Association of Serum Circulating Neuropeptide Q and Chemerin Levels with Cardiometabolic Risk Factors among Patients with Metabolic Syndrome.

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population (p < 0.00000001, R2adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.

Circulating CTRP7 Is a Potential Predictor for Metabolic Syndrome.

Background: Previous animal studies have revealed that CTRP7 is related to energy metabolism. However, little is known regarding the relationship between CTRP7 and metabolic diseases in humans. Hence, this study was designed to explore the association between CTRP7 and MetS through a cross-sectional study and multiple intervention studies. Methods: A total of 624 individuals were enrolled in this study. The levels of CTRP7 and APN were determined by ELISA kit. HEC, OGTT and lipid infusion were performed in heathy individuals to investigate the association of CTRP7 and glucose, insulin and FFA. Bioinformatics analysis was then undertaken to identify genes and signaling pathways associated with CTRP7. The relationship between CTRP7 with MetS components was also evaluated. Results: In MetS patients, serum CTRP7 concentrations were significantly higher than in healthy controls, and was positively correlated with WC, BP, FBG, 2h-BG and TG, but negatively correlated with HDL-C and APN. Multivariate logistic regression analysis uncovered that CTRP7 was strongly correlated with the occurrence of MetS. In addition, circulating levels of CTRP7 in patients with two or more MetS components were higher than those with one MetS component. In the intervention studies, OGTTs resulted in a significant reduction in serum CTRP7 concentration. However, the increase in insulin levels caused by EHC and the increase of FFA caused by lipid-infusion led to the significant increase of serum CTRP7 concentration. Meanwhile, bioinformatics analysis revealed that CTRP7 was strongly associated with metabolism-related genes and signal pathways, which further illustrate the association of CTRP7 with whole-body metabolism. Conclusions: Serum CTRP7 is increased in MetS patients, which may be a biomarker related to metabolic diseases. Clinical Trial Registration Number: ChiCTR2000032878.

Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model.

Metabolic syndrome (MS) is a risk factor for type 2 diabetes mellitus, vascular inflammation, atherosclerosis, and renal, liver, and heart diseases. Non-alcoholic steatohepatitis (NASH) is a progressive representative liver disease and may lead to the irreversible calamities of cirrhosis and hepatocellular carcinoma. Metabolic disorders such as hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between hyperglycemia and carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop metabolic syndrome, including obesity, insulin resistance, and NASH-like liver phenotype, and eventually develop hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in blood glucose levels, body weights, and pancreatic and liver lesions over time. As a result, liver carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of oligosaccharide that could lower blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived oligosaccharides (galactooligosaccharides and lactosucrose). At the age of 24 weeks, mild steatohepatitis was found in the liver but there was no evidence of liver carcinogenesis. Steatosis in the liver was alleviated in the milk-derived oligosaccharide-administered group. Taken together, suppressing the increase in blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of NAFLD/NASH, as well as carcinogenesis. Milk-derived oligosaccharides showed a lowering effect on blood glucose levels, which may be expected to prevent liver carcinogenesis.

Athrixia phylicoides tea infusion (bushman tea) improves adipokine balance, glucose homeostasis and lipid parameters in a diet-induced metabolic syndrome rat model.

BACKGROUND: Central obesity and insulin resistance are associated with metabolic syndrome (MetS) which is aggravated by diet and sedentary lifestyle. Athrixia phylicoides (AP) is reported by rural communities to have medicinal benefits associated with MetS such as obesity and type 2 diabetes. This study was aimed to investigate the effects of AP on diet-induced MetS in Wistar rats to validate its ethnopharmacological use. METHODS: AP was profiled for phytochemicals by LC-MS. After induction of MetS with high energy diet (HED), 30 male rats were divided into five treatment groups (n = 6): normal diet control, HED control, HED + AP 50 mg/Kg BW, HED + AP 100 mg/Kg BW and HED + 50 mg/Kg BW metformin. The rats were treated daily for 8 weeks orally after which weight gain, visceral fat, total cholesterol, free fatty acids (FFAs) and adipokine regulation; leptin: adiponectin ratio (LAR) were assessed. Also, glucose homeostatic parameters including fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose transporter 4 (GLUT 4), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. RESULTS: Findings showed that AP was rich in polyphenols. The HED control group showed derangements of the selected blood parameters of MetS. AP reversed diet-induced weight gain by reducing visceral fat, total blood cholesterol and circulating FFAs (p ≤ 0.05). Treatment with AP improved adipokine regulation depicted by reduced LAR (p<0.05). Treatment with AP improved parameters of glucose homeostasis as demonstrated by reduced FBG and HOMA-IR (p ≤ 0.05) and increased GLUT 4 (p<0.05). CONCLUSION: Athrixia phylicoides tea infusion was shown to possess anti-obesity and anti-inflammatory properties, improved glucose uptake and reduce insulin resistance in diet-induced MetS in rats which could be attributed to its richness in polyphenols. Therefore, AP could have potential benefits against type 2 diabetes and obesity which are components of MetS validating its ethnopharmacological use.

The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect.

Incretin hormones are peptides released in the intestine in response to the presence of nutrients in its lumen. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 stimulates insulin secretion, inhibits glucagon secretion at pancreatic α cells and has also extrapancreatic influences as slowing of gastric emptying which increases the feeling of satiety. GIP is the main incretin hormone in healthy people, causative of most the incretin effects, but the insulin response after GIP secretion in type 2 diabetes mellitus (T2DM) is strongly reduced. Therefore, in the past GIP has been considered an unappealing therapeutic target for T2DM. This conception has been changing during recent years, since it has been reported that resistance to GIP can be reversed and its effectiveness restored by improving glycemic control. This fact paved the way for the development of a GIP receptor agonist-based therapy for T2DM, looking also for the possibility of finding a combined GLP-1/GIP receptor agonist. In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as a subcutaneous weekly injection, it is a manifold single pharmacological agent that has the ability to significantly lower glucose levels, as well as improve insulin sensitivity, reduce weight and amend dyslipidemia favorably modifying the lipid profile. Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. Obviously, it is too early to be overly hopeful since it is still necessary to determine the long-term effects of these compounds and properly verify the potential cardiovascular benefits. Anyway, we are currently facing a novel and very appealing therapeutic option.

APOE ɛ4 Is Associated with Postprandial Inflammation in Older Adults with Metabolic Syndrome Traits.

The apolipoprotein E (APOE) polymorphism impacts blood lipids and biomarkers of oxidation and inflammation, contributing to an isoform-dependent disease risk. We investigated the effect of the APOE genotype on postprandial metabolism after consumption of three different isoenergetic (4200 kJ) meals in older adults with a CVD risk phenotype. In a randomized crossover study, participants with metabolic syndrome traits (APOE E3, n = 39; E4, n = 10; mean age, 70 ± 5 years; BMI 31.3 ± 3.0 kg/m2) consumed a Western-like diet high-fat (WDHF), Western-like diet high-carbohydrate (WDHC), or Mediterranean-like diet (MED) meal. Parameters of lipid and glucose metabolism, inflammatory, and oxidative parameters were analyzed in blood samples collected at fasting and 1-5 h postprandially. Data were analyzed by linear mixed models. The magnitude of the IL-6 increase after the WDHF meal was significantly higher in E4 than in E3 carriers (iAUC: E4 = 7.76 vs. E3 = 2.81 pg/mL × h). The time to detect the IL-6 increase was shorter in the E4 group. All meals produced postprandial glycemia, insulinemia, and lipidemia, without differences between the E3 and the E4 groups. IL-1ß and oxidized LDL levels did not change postprandially. In conclusion, APOE E4 carriers display increased postprandial inflammation, indicated by higher postprandial IL-6 increase, when compared to non-carriers.

The effects of consuming a low-fat yogurt fortified with nano encapsulated vitamin D on serum pro-oxidant-antioxidant balance (PAB) in adults with metabolic syndrome; a randomized control trial.

BACKGROUND AND AIM: The current study aimed to assess the effect of fortified yogurt with nano-encapsulated vitamin D on serum pro-oxidant anti-oxidant balance (PAB) in adults with or without metabolic syndrome. METHODS: In a quadruple blind clinical trial study, 139 adults with an age range of 30-50 years were randomly selected to receive either 1500 IU nano-encapsulated vitamin D fortified yogurt or placebo for ten weeks. Before and after the intervention period, blood sample was taken to determine the serum levels of vitamin D, pro-oxidant-antioxidant balance (PAB), and high-sensitivity C-reactive protein (hs-CRP). The laboratory tests were checked at baseline and at the end of the treatment. RESULTS: Serum vitamin D increased significantly, from 14.47 ± 6.07 ng/mL to 21.39 ± 6.54 ng/mL (P < 0.001) after ten weeks in the intervention group. Serum hs-CRP and PAB were significantly lower following consumption period in intervention group [1.95(0.4-8.15) g/dL vs. 1.35(0.25-3.62) g/dL; P = 0.013] and (135.19 ± 42.4 HK vs. 115.39 ± 44.69) HK; P = 0.018] respectively. There were no significant differences between the intervention and control groups regarding weight and BMI at the end of the intervention period (p > 0.05). CONCLUSION: Low-fat yogurt fortified with nano-encapsulated vitamin D was found to reduce serum PAB levels in adults with metabolic syndrome. PRACTICAL APPLICATION: The findings of the present study indicated that a low-fat yogurt fortified with 1500 IU nano-encapsulated vitamin D for ten weeks, leads to a significant reduction in serum hs-CRP and PAB concentrations highlighted the anti-inflammatory/anti-oxidative effect of vitamin D.

Antibodies against phosphorylcholine in hospitalized versus non-hospitalized obese subjects.

Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospitalized obese. One-hundred-and-twenty-eight obese (BMI ≥ 30 kg/m2) individuals (59.8 (± 5.5) years, 53.9% women) from the Malmö Diet and Cancer Cardiovascular Cohort were examined and IgM, IgG1 and IgG2 anti-PC were analyzed by ELISA. Individuals with at least one recorded history of hospitalization prior to study baseline were considered hospitalized obese (HO). Associations between IgM, IgG1 and IgG2 anti-PC and HO (n = 32)/non-hospitalized obese (NHO) (n = 96), but also with metabolic syndrome and diabetes were analysed using logistic regressions. Both IgM and IgG1 anti-PC were inversely associated with HO, also after controlling for age and sex. When further adjusted for waist circumference, systolic blood pressure, glucose levels and smoking status, only IgG1 anti-PC remained significantly associated with HO. In multivariate models, each 1 standard deviation of increment in anti-PC IgG1 levels was inversely associated with prevalence of HO (odds ratio 0.57; CI 95% 0.33-0.98; p = 0.044). IgG2 anti-PC did not show any associations with HO. Low levels of IgM and IgG1 anti-PC are associated with higher risk of being a HO individual independent of sex and age, IgG1 anti-PC also independently of diabetes and metabolic syndrome. The anti-inflammatory properties of these antibodies may be related to inflammation in obesity and its complications.

Association of EDARV370A with breast density and metabolic syndrome in Latinos.

The ectodysplasin receptor (EDAR) is a tumor necrosis factor receptor (TNF) superfamily member. A substitution in an exon of EDAR at position 370 (EDARV370A) creates a gain of function mutant present at high frequencies in Asian and Indigenous American populations but absent in others. Its frequency is intermediate in populations of Mexican ancestry. EDAR regulates the development of ectodermal tissues, including mammary ducts. Obesity and type 2 diabetes mellitus are prevalent in people with Indigenous and Latino ancestry. Latino patients also have altered prevalence and presentation of breast cancer. It is unknown whether EDARV370A might connect these phenomena. The goals of this study were to determine 1) whether EDARV370A is associated with metabolic phenotypes and 2) if there is altered breast anatomy in women carrying EDARV370A. Participants were from two Latino cohorts, the Arizona Insulin Resistance (AIR) registry and Sangre por Salud (SPS) biobank. The frequency of EDARV370A was 47% in the Latino cohorts. In the AIR registry, carriers of EDARV370A (GG homozygous) had significantly (p < 0.05) higher plasma triglycerides, VLDL, ALT, 2-hour post-challenge glucose, and a higher prevalence of prediabetes/diabetes. In a subset of the AIR registry, serum levels of ectodysplasin A2 (EDA-A2) also were associated with HbA1c and prediabetes (p < 0.05). For the SPS biobank, participants that were carriers of EDARV370A had lower breast density and higher HbA1c (both p < 0.05). The significant associations with measures of glycemia remained when the cohorts were combined. We conclude that EDARV370A is associated with characteristics of the metabolic syndrome and breast density in Latinos.