Corrigendum: Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects.

[This corrects the article DOI: 10.1177/1535370220962708.].

Serum kisspeptin is higher in hypertensive than non-hypertensive female subjects and positively correlated with systolic blood pressure.

BACKGROUND: Kisspeptin has a major role in reproductive regulation. Furthermore, it is also involved in metabolic and cardiovascular regulation as well as is a potent vasoconstrictor. This study aimed to: 1) determine correlations between serum kisspeptin levels with obesity/metabolic parameters; 2) compare parameters between non-hypertensive ([non-HT] N.=15) and hypertensive ([HT] N.=15) female subjects; and 3) determine correlations between leptin, systolic blood pressure (SBP) or diastolic blood pressure (DBP) with obesity and metabolic factors. METHODS: Clinical parameters and fasting blood and adipose tissue samples were collected from women undergoing open abdominal surgery. RESULTS: Serum kisspeptin was not correlated with obesity parameters but was positively correlated with only SBP (P<0.05). Serum kisspeptin, SBP, DBP, body weight, waist circumference, hip circumference, plasma glucose, plasma insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and height of visceral adipocytes (VA) were higher but the Quantitative Insulin Sensitivity Check Index (QUICKI) was lower in hypertensive compared to non-hypertensive female subjects (P<0.05). Leptin was positively correlated with obesity and metabolic paramters including area, width, and perimeter of subcutaneous adipocytes, and area, width, height, and perimeter of VA (P<0.05) but was negatively correlated the QUICKI (P<0.001). SBP had positive correlations with insulin, glucose, HOMA-IR, and kisspeptin, but had a negative correlation with QUICKI (P<0.05). DBP had positive correlations with body weight, BMI, waist circumference, hip circumference, insulin, glucose, HOMA-IR, and width of VA (P<0.05), but had a negative correlation with the QUICKI (P<0.05). CONCLUSIONS: Kisspeptin, obesity especially visceral adiposity, and insulin resistance might contribute to increased blood pressure. Further studies are required to reveal the underlying mechanism of kisspeptin on metabolic and cardiovascular regulation.

A Longitudinal Study of the Relationship of Adiponectin with Reproduction in Infertile Women Undergoing IVF/ICSI Treatment, and an Experimental Study in Human Granulosa Cells.

This study investigated the roles of adiponectin in IVF treatment during Phase I (the basal stage before gonadotropin administration), Phase II (approximately 8 days after gonadotropin administration), and Phase III (on the ovum pick-up day), as well as the effects of adiponectin on CYP19A1 and the FSH receptor (FSHR) mRNA expression in a human granulosa-like tumor cell line (KGN). In human subjects (a longitudinal study, n = 30), blood samples were collected in all phases, while follicular fluid (FF) was only collected in Phase III. The participants were classified into successful and unsuccessful groups based on the determination of fetal heartbeats. KGN cells were treated with adiponectin/FSH/IGF-1 (an experimental study, n = 3). There was no difference in the adiponectin levels between successful and unsuccessful pregnancies in the FF (Phase III) and in serum (all phases), as well as among the three phases in both groups. Serum FSH (Phase I) was positively associated with serum adiponectin in the unsuccessful group, but it had a negative association in the successful group (all phases). Serum adiponectin and serum FSH (Phase I) were positively correlated in the unsuccessful group, whereas they were negatively correlated (all phases) in the successful group. The serum adiponectin levels (Phase III) were significantly higher than in the FF in unsuccessful pregnancies, but there was no difference in successful pregnancies. FF adiponectin concentrations were negatively correlated with serum LH in successful subjects. In KGN cells, adiponectin had no influence on CYP19A1 and FSHR mRNA expression. High adiponectin levels in serum compared to FF (Phase III) in unsuccessful subjects might negatively impact IVF treatment.

Cissus Quadrangularis enhances UCP1 mRNA, indicative of white adipocyte browning and decreases central obesity in humans in a randomized trial.

Obesity is associated with the growth and expansion of adipocytes which could be decreased via several mechanisms. Cissus Quadrangularis (CQ) extract has been shown to reduce obesity in humans; however, its effect on human white adipocytes (hWA) has not been elucidated. This study aimed to investigate the effects of CQ on obesity, lipolysis, and browning of hWA. CQ treatment in obese humans significantly decreased waist circumference at week 4 and week 8 when compared with the baseline values (p < 0.05 all) and significantly decreased hip circumference at week 8 when compared with the baseline and week 4 values (p < 0.05 all). Serum leptin levels of the CQ-treated group were significantly higher at week 8 compared to baseline levels (p < 0.05). In hWA, glycerol release was reduced in the CQ-treated group when compared with the vehicle-treated group. In the browning experiment, pioglitazone, the PPAR-γ agonist, increased UCP1 mRNA when compared to vehicle (p < 0.01). Interestingly, 10, 100, and 1000 ng/ml CQ extract treatment on hWA significantly enhanced UCP1 expression in a dose-dependent manner when compared to pioglitazone treatment (p < 0.001 all). In conclusion, CQ decreased waist and hip circumferences in obese humans and enhanced UCP1 mRNA in hWA suggestive of its action via browning of hWA.

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects.

Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.

Associations of serum kisspeptin levels with metabolic and reproductive parameters in men.

Central kisspeptin action is well known in reproductive regulation; however, its peripheral action is not well understood. This study aimed to 1) compare serum or cerebrospinal fluid (CSF) kisspeptin levels between different body mass index (BMI) groups 2) compare the levels of kisspeptin between serum and CSF, and 3) determine correlations between serum or CSF kisspeptin levels with clinical, metabolic, and reproductive parameters. There were 40 male subjects undergoing operations with lumbar puncture anesthesia. Subgroup analysis was performed to compare between the normal (n = 12), overweight (n = 10), and obese groups (n = 17). One lean subject was recruited for correlation analysis. Serum kisspeptin levels were significantly higher in the obese group when compared to the normal weight and overweight groups even after adjusting for age or diastolic blood pressure (DBP) (p < 0.05 all). Serum leptin levels were significantly higher in the obese group when compared to the normal weight and overweight groups (p < 0.05 all). CSF kisspeptin levels were below the minimum detectable concentration for the assay (<0.06 ng/mL). Serum kisspeptin was positively correlated with body weight, BMI, plasma insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum leptin but was negatively correlated with plasma LH (p < 0.05 all). In conclusion, serum kisspeptin was related to obesity, leptin, insulin, and insulin resistance, while CSF kisspeptin was below the limits of detection. Thus, peripheral kisspeptin might have a role in metabolic regulation.

Factors influencing the National License Examination step 1 score in preclinical medical students.

The National License Examination step 1 (NLE1), which tests basic medical sciences knowledge in Thailand, is considered to be tough and stressful for medical students due to the large amount of content. This study aimed to determine factors influencing the NLE1 score (NLE1S). The NLE1S, academic achievement, and class attendance were obtained officially. Other factors, including study habits, were obtained via a questionnaire, with 81.97% (241/294) being returned. Students were divided into four groups according to the central passing score and Z-score of the NLE1S, including the fail (<52%; n = 13), low-pass (52 to <70%; n = 121), high-pass (70 to <80%; n = 89), and excellent (≥80%; n = 18) groups. Men had higher NLE1S (P < 0.001) and comprehensive examination scores (P < 0.001) than women. Students with high motivation to study medicine had higher NLE1S. Daily preparation time (h/day) was lower, but stress was higher, in the fail group. In the excellent group, internet for academic use and achievement of study targets were higher; internet for nonacademic use, instance of absence, and stress were lower; and check-in time was earlier. The NLE1S had strong positive correlations with the comprehensive examination score and academic achievement during preclinical studies. By setting the NLE1S as a dependent variable in multivariate regression analyses, models of significant interactions were observed by setting behavioral factors, the comprehensive examination score, and academic achievement during a regular class as independent variables. Thus exhibiting good study habits and showing good academic performance throughout preclinical studies should be encouraged among students to achieve a good NLE1S.

Adipose Y5R mRNA is higher in obese than non-obese humans and is correlated with obesity parameters.

Neuropeptide Y is mainly expressed in the central nervous system to regulate food intake via its receptors, Y receptors, and in various peripheral tissues including adipose tissue. The objectives of this study were to compare Y5R mRNA and adipocyte parameters consisting of area, width, height, and perimeter either between obese and non-obese subjects or between subcutaneous and visceral fat as well as to compare between NPY, Y1R, Y2R, and Y5R mRNA expressions in subcutaneous and visceral adipose tissues. In subcutaneous and visceral adipose tissues, Y5R was greater in obese than in non-obese humans (both P < 0.05). Y1R mRNA expression was highest followed by Y5R, Y2R, and NPY mRNA expressions, respectively, in subcutaneous and visceral adipose tissues. Visceral Y5R mRNA had positive correlations with body weight, body mass index, waist circumference, hip circumference (R ≍ 0.4), and visceral Y1R mRNA (R = 0.773), but had a negative correlation with the quantitative insulin sensitivity check index (R=-0.421) (all P < 0.05). Subcutaneous and visceral adipocyte parameters were positively correlated with body weight, waist circumference, hip circumference, and waist-to-hip ratio, with greater values of correlation coefficient shown in visceral (R ≍ 0.5-0.8) than in subcutaneous adipocytes (R ≍ 0.4-0.6, all P < 0.05). The parameters of visceral adipocytes had positive correlations with serum NPY levels (R ≍ 0.4, all P < 0.05). Y5R mRNA in visceral adipose tissue is related to increased obesity and reduced insulin sensitivity. The dominant Y receptors in subcutaneous and visceral adipose tissue might be the Y1R and Y5R. Visceral adipocytes show higher correlations with obesity parameters than subcutaneous adipocytes, suggestive of an increased risk of metabolic syndrome in visceral obesity. Y1R and Y5R in visceral adipose tissue might be targets of drug development in prevention or treatment of adiposity. Impact statement Obesity, defined as excess fat accumulation, has been increasingly diagnosed worldwide causing adverse health consequences. The novel findings of this study were that Y5R mRNA expression in both subcutaneous and visceral fat was higher in obese than non-obese subjects. Furthermore, Y5R only in visceral fat, not subcutaneous fat, was positively correlated with visceral Y1R and obesity parameters but it was negatively correlated with the QUICKI. Moreover, we found that Y1R expression was highest followed by Y5R and Y2R, respectively, in both subcutaneous and visceral fat. Our results suggested that Y5R in visceral fat was associated with increased obesity and decreased insulin sensitivity. Y1R and Y5R might be the dominant receptors that mediate the effect of NPY-induced fat accumulation in both subcutaneous and visceral adipose tissues. Y1R and Y5R in visceral adipose tissue might be targets of drug development in prevention or treatment of obesity.

Corrigendum to: Increased high molecular weight adiponectin, but decreased total adiponectin and kisspeptin, in central precocious puberty compared with aged-matched prepubertal girls.

The aim of the present study was to compare serum leptin, kisspeptin, total adiponectin, high molecular weight (HMW) adiponectin and neuropeptide Y (NPY) levels between girls with central precocious puberty (CPP; n=26, 7-9.5 years old) and age-matched controls (n=29) including or excluding obese girls. Leptin and NPY levels were comparable between CPP and control girls. Kisspeptin levels were lower in the CPP than control group, and were positively correlated with oestrogen in the control group and with systolic and diastolic blood pressure in the CPP group. Kisspeptin levels were negatively correlated with FSH and LH in the CPP group. Total adiponectin levels were lower in CPP than control girls, and were negatively correlated with Tanner stage and body mass index, but positively correlated with the quantitative insulin sensitivity check index in the control group. HMW adiponectin was higher in the CPP than control group, and was positively correlated with Tanner stage and LH in all girls. Total adiponectin had a strong positive correlation with HMW adiponectin in the CPP group (r=0.915) compared with the control group (r=0.371). In conclusion, kisspeptin may be associated with increased oestrogen in prepubertal girls, but with increased blood pressure in girls with CPP. In girls entering puberty, HMW adiponectin was increased and associated with reproductive parameters. Based on these observations, HMW adiponectin probably plays an essential role in the initiation of puberty and is a candidate marker for the prediction of CPP.

Increased high molecular weight adiponectin, but decreased total adiponectin and kisspeptin, in central precocious puberty compared with aged-matched prepubertal girls.

The aim of the present study was to compare serum leptin, kisspeptin, total adiponectin, high molecular weight (HMW) adiponectin and neuropeptide Y (NPY) levels between girls with central precocious puberty (CPP; n=26, 7-9.5 years old) and age-matched controls (n=29) including or excluding obese girls. Leptin and NPY levels were comparable between CPP and control girls. Kisspeptin levels were lower in the CPP than control group, and were positively correlated with oestrogen in the control group and with systolic and diastolic blood pressure in the CPP group. Kisspeptin levels were negatively correlated with FSH and LH in the CPP group. Total adiponectin levels were lower in CPP than control girls, and were negatively correlated with Tanner stage and body mass index, but positively correlated with the quantitative insulin sensitivity check index in the control group. HMW adiponectin was higher in the CPP than control group, and was positively correlated with Tanner stage and LH in all girls. Total adiponectin had a strong positive correlation with HMW adiponectin in the CPP group (r=0.915) compared with the control group (r=0.371). In conclusion, kisspeptin may be associated with increased oestrogen in prepubertal girls, but with increased blood pressure in girls with CPP. In girls entering puberty, HMW adiponectin was increased and associated with reproductive parameters. Based on these observations, HMW adiponectin probably plays an essential role in the initiation of puberty and is a candidate marker for the prediction of CPP.

Correlations between the expression of the insulin sensitizing hormones, adiponectin, visfatin, and omentin, and the appetite regulatory hormone, neuropeptide Y and its receptors in subcutaneous and visceral adipose tissues.

Adiponectin, visfatin, and omentin are adipokines involved in insulin sensitivity. Neuropeptide Y (NPY) and its receptors, Y1R, Y2R, and Y5R, are involved in appetite regulation. Here we examined the correlations between these two hormones groups in subcutaneous and visceral adipose tissues. We demonstrated that in subcutaneous adipose tissue, the adiponectin, visfatin and omentin expression positively correlated with that of subcutaneous NPY. Subcutaneous adiponectin expression positively correlated with subcutaneous Y1R and Y5R. Subcutaneous visfatin expression positively correlated with subcutaneous Y1R, Y2R, and Y5R. Subcutaneous omentin expression positively correlated with subcutaneous Y5R. In visceral adipose tissue, adiponectin, visfatin and omentin expression positively correlated with visceral NPY. Visceral visfatin expression positively correlated with visceral Y1R, Y2R and Y5R. There was no correlation between the subcutaneous and visceral expression of these adipokines and receptors. BMI correlated better with visceral adipocyte characteristics including width, height, perimeter, and area than with those of subcutaneous adipocyte. Visceral, but not subcutaneous, adipocyte parameters positively correlated with insulin and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), but negatively associated with Quantitative Insulin Sensitivity Check Index (QUICKI). These results suggest that adiponectin, omentin, and visfatin expression correlated with NPY expression in either type of adipose tissue, with no evidence of cross-linking between adipose tissue depots, suggesting that there might be (a) different regulation mechanism(s) between subcutaneous and visceral adipose tissues with regard to expressions of these two hormone groups. Further studies are required to identify factors that regulate the linkage between these hormones in each adipose tissue type.

Interactions between adiponectin, visfatin, and omentin in subcutaneous and visceral adipose tissues and serum, and correlations with clinical and peripheral metabolic factors.

Adiponectin, visfatin, and omentin are adipokines involved in insulin sensitivity. This study aimed to determine interactions between these adipokines in subcutaneous and visceral fat and in serum, and their associations with clinical factors. Adiponectin was present at the highest levels in subcutaneous and visceral fat and serum. Subcutaneous adiponectin showed positive correlations with serum adiponectin and the quantitative insulin sensitivity check index (QUICKI). Serum adiponectin correlated positively with QUICKI and serum omentin-1 but negatively with body weight, BMI, and homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous omentin correlated positively with QUICKI but negatively with waist and hip circumferences. Serum omentin-1 correlated positively with QUICKI but negatively with body weight, BMI, waist and hip circumferences, weight gain, and HOMA-IR. Serum visfatin correlated positively with serum omentin-1 and negatively with weight gain. Serum peptide YY (PYY) levels were correlated positively with subcutaneous visfatin but negatively with visceral visfatin. Positive correlations were observed between subcutaneous expression of adiponectin, visfatin, and omentin and visceral expression of these genes. Multiple linear regression analysis showed that serum adiponectin was associated with BMI and QUICKI. Serum omentin-1 could be predicted from BMI, QUICKI, and weight gain. Weight gain, serum adiponectin, omentin-1, and DBP could be used to predict serum visfatin. In conclusion, adiponectin and omentin from subcutaneous fat displayed correlations with decreased obesity and increased insulin sensitivity while visfatin showed an association with serum PYY and weight gain. The expressions of these adipokines were correlated within each type of fat but not between different fat depots.