Unraveling the role of resistin, retinol-binding protein 4 and adiponectin produced by epicardial adipose tissue in cardiac structure and function: evidence of a paracrine effect.

PURPOSE: Adipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin produced by epicardial adipose tissue with coronary artery disease (CAD) and cardiac structure and function. METHODS: Forty-one non-diabetic males scheduled for cardiothoracic surgery were examined. Anthropometric measurements, echocardiography, coronary angiography, and blood analysis were performed preoperatively. We measured the serum levels of resistin, RBP4, and adiponectin and their mRNA expression in thoracic subcutaneous adipose tissue and two epicardial adipose tissue samples, one close to left anterior descending artery (LAD) (resistin-LAD, RBP4-LAD, adiponectin-LAD), and another close to the right coronary artery (RCA) (resistin-RCA, RBP4-RCA, adiponectin-RCA). RESULTS: Left ventricular (LV) ejection fraction correlated negatively with adiponectin-LAD (rho = - 0.390, p = 0.025). The ratio of early to late diastolic transmitral flow velocity, as an index of LV diastolic function, correlated negatively with resistin-LAD (rho = - 0.529, p = 0.024) and RBP4-LAD (rho = - 0.458, p = 0.049). There was no difference in epicardial adipose tissue mRNA expression of resistin, RBP4, and adiponectin between individuals with CAD and those without CAD. When we compared the individuals with CAD in the LAD with those without CAD in the LAD, there was no difference in resistin-LAD, RBP4-LAD, and adiponectin-LAD. There was no difference in resistin-RCA, RBP4-RCA, and adiponectin-RCA between the individuals with CAD in the RCA and those without CAD in the RCA. CONCLUSION: Elevation of epicardial adipose tissue mRNA expression of adiponectin was associated with LV systolic dysfunction, while that of both resistin and RBP4 was linked to LV diastolic dysfunction.

The regulation of serum resistin levels in metabolically healthy and unhealthy obese individuals.

PURPOSE: We have recently demonstrated that absolute counts of circulating proinflammatory monocytes were lower in obese patients without metabolic syndrome (MS) (metabolically healthy obese, MHO) compared with those with MS (metabolically unhealthy obese, MUO), but higher compared with healthy lean controls (MHL). We hypothesized that circulating resistin, a cytokine secreted by white blood cells (WBC), is involved in obesity-related low-grade inflammation. The aim of this study was to (a) determine serum resistin levels among MUO and MHO subjects and (b) investigate the role of circulating WBC subsets as potential determinants of resistin. METHODS: Study participants were 58 obese (33 MUO, 25 MHO) and 25 MHL individuals. Serum levels of resistin, high-sensitivity C-reactive protein (hsCRP), and absolute counts of circulating WBC subpopulations were determined. Comparisons were sex- and age-adjusted. RESULTS: Serum resistin levels in MHL were lower compared with those of obese (p = 0.041), but similar to those of MHO (p = 0.856) individuals. Both resistin (p = 0.005) and absolute neutrophil count (NeuA) (p = 0.025) were higher in MUO compared with MHO. The difference in resistin levels between obese and MHL individuals disappeared after adjustment for NeuA. Resistin correlated positively with absolute total monocyte count (p = 0.037) in MHL and with body mass index (BMI) (p = 0.023), hsCRP (p = 0.022), and NeuA (p = 0.044) in obese subjects. Resistin association with ΒΜΙ disappeared after adjustment for hsCRP, while association with hsCRP disappeared after further adjustment for NeuA. CONCLUSION: Circulating resistin was higher in MUO compared with MHO. The increased secretion of resistin by the greater number of neutrophils in the former may have contributed to this regulation.

The effect of follicular phase length on cycle outcomes and endometrial development in gonadotrophin ovarian stimulation/intrauterine insemination cycles.

RESEARCH QUESTION: Does a shorter follicular phase length (FPL) affect cycle outcomes and endometrial development among women undergoing gonadotrophin ovarian stimulation/intrauterine insemination (OS/IUI)? DESIGN: Retrospective cohort study of 4773 OS/IUI cycles among 2054 patients. FPL was analysed first continuously, then dichotomously using an arbitrary cut-off at the 15th percentile (8 days) to divide cycles into shorter and longer FPL groups. Receiver operating characteristic (ROC) curves were constructed to further analyse the impact of FPL on all outcomes. Primary outcomes included clinical pregnancy, spontaneous abortion, multiple pregnancy and non-viable (ectopic/biochemical) pregnancy rates (CPR, SABR, MPR and NVPR, respectively). Secondary outcomes included endometrial thickness. All analyses controlled for age, day 3 FSH and body mass index. RESULTS: When analysing FPL continuously, CPR increased by 6.0% (adjusted odds ratio [aOR] 1.06, 95% CI 1.03-1.09, P < 0.001) with each additional follicular phase day. Similarly, in the dichotomous analysis, cycles with a longer FPL resulted in higher CPR with 45% higher odds of clinical pregnancy (aOR 1.45, 95% CI 1.07-1.97, P = 0.018). No effect of FPL was noted on NVPR, SABR or MPR. Endometrial thickness increased by 0.09 mm (95% CI 0.06-0.12, P < 0.001) with each additional FPL day and was increased in the longer compared with the shorter FPL group (adjusted mean difference 1.08 mm, 95% CI 0.81-1.34, P < 0.001). CONCLUSIONS: The data suggest that in gonadotrophin OS/IUI cycles, FPL might impact both chance of clinical pregnancy and endometrial thickness, independent of maternal age and ovarian reserve.

Indirect clinical markers for the detection of anabolic steroid abuse beyond the conventional doping control in athletes.

Growing analytical challenges have arisen for the detection of misuse of androgenic anabolic steroids (AAS) in athletes the last years. Therefore, consideration of additional indirect markers can substantially aid the efforts to detect AAS abuse in athletes. Moreover, this approach can also help physicians to suspect AAS abuse when treating athletes. Laboratory markers highly indicative of AAS abuse in athletes include the considerable downregulation of high density lipoprotein-cholesterol, elevation of haematocrit or serum γ-glutamyl transpeptidase levels and for males reduced serum levels of both luteinizing hormone and follicle-stimulating hormone. Moreover, physical signs suggestive of current AAS abuse are hypertension, apparent changes in behaviour making the athlete more irritable and aggressive and the sudden appearance of acne vulgaris in an adult athlete with no recent history of acne, while testicular atrophy and gynecomastia raise suspicion of current or past AAS abuse in male athletes.

Semaglutide as a promising antiobesity drug.

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

OBJECTIVE: The elucidation of the changes of fetuin-A in the context of bariatric surgery. DESIGN: Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. RESULTS: Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). CONCLUSIONS: Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation.

BACKGROUND: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. METHODS: A literature search based on PubMed listings was performed using "Omega-3 fatty acids" and "atrial fibrilation" as key search terms. RESULTS: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. CONCLUSIONS: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions.

The efficacy and safety of the naltrexone/bupropion combination for the treatment of obesity: an update.

OBJECTIVE: The combination of 32 mg naltrexone and 360 mg bupropion prolonged release (NB32) was recently approved by both the food and drug administration (FDA) and the European medicines agency (EMA) as an adjunct to a comprehensive lifestyle intervention to achieve weight loss. DESIGN: Randomized controlled trials with naltrexone/bupropion prolonged release were selected through a search based on PubMed listings using the terms "bupropion AND naltrexone". RESULTS: NB32 treatment resulted in 5.0-9.3% weight loss, while the placebo-subtracted weight loss was 3.2-5.2% during 56 weeks of treatment. The proportion of treated patients with ≥ 5% weight loss was 45-66%, while the placebo-subtracted proportion was 23-34%. NB32 was associated with a decrease in waist circumference, serum triglycerides and insulin resistance and an increase in high-density lipoprotein-cholesterol (HDL-C). Blood pressure mainly remained stable but there was a small increase in heart rate. The most common side effects were nausea, constipation, headache and vomiting. Serious adverse effects, which were very rare, included suicidal thoughts and seizures. In the majority of patients NB32 treatment was well tolerated. CONCLUSIONS: Naltrexone/bupropion combination appears to be an effective adjunct to a comprehensive lifestyle intervention in order to achieve weight loss and treat obesity-related comorbidities.