Bone Quality Indices Correlate with Growth Hormone Secretory Capacity in Women Affected by Weight Excess: A Cross-Sectional Study.

Background/Objectives: Obesity can be associated with impaired growth hormone (GH) secretion, with possible negative repercussions on bone health. We aimed to investigate the relationships between GH secretory capacity, evaluated with GHRH + arginine stimulation test, and bone parameters, assessed with a dual-energy X-ray absorptiometer, in a population of adult female patients affected by overweight and obesity. Methods: We assessed 276 women affected by overweight or obesity referred to the High-Specialization Center for the Care of Obesity, Umberto I Polyclinic, between 2014 and 2019 with signs or symptoms of growth hormone deficiency (GHD). Results: A total of 97 patients were diagnosed with GHD, and 179 patients with normal GH secretion were considered our control group. GHD patients showed a significantly reduced trabecular bone score (TBS) (p = 0.01). Bone quality parameters corrected for body mass index (BMI) had a positive and significant linear correlation with stimulated GH secretory capacity. Conclusions: In conclusion, bone quality, evaluated by TBS and hip structural analysis, correlates with GH-stimulated secretory capacity. GHD may act as an additive factor in the alteration of bone microarchitecture in patients affected by obesity, who are already at a higher risk of fractures.

Energy Metabolism and Metformin: Effects on Ischemia-Reperfusion Injury in Kidney Transplantation.

Metformin (MTF) is the only biguanide included in the World Health Organization's list of essential medicines; representing a widespread drug in the management of diabetes mellitus. With its accessibility and affordability being one of its biggest assets, it has become the target of interest for many trying to find alternative treatments for varied pathologies. Over time, an increasing body of evidence has shown additional roles of MTF, with unexpected interactions of benefit in other diseases. Metformin (MTF) holds significant promise in mitigating ischemia-reperfusion injury (IRI), particularly in the realm of organ transplantation. As acceptance criteria for organ transplants expand, IRI during the preservation phase remain a major concern within the transplant community, prompting a keen interest in MTF's effects. Emerging evidence suggests that administering MTF during reperfusion may activate the reperfusion injury salvage kinase (RISK) pathway. This pathway is pivotal in alleviating IRI in transplant recipients, potentially leading to improved outcomes such as reduced rates of organ rejection. This review aims to contextualize MTF historically, explore its current uses, pharmacokinetics, and pharmacodynamics, and link these aspects to the pathophysiology of IRI to illuminate its potential future role in transplantation. A comprehensive survey of the current literature highlights MTF's potential to recondition and protect against IRI by attenuating free radical damage, activating AMP-activated protein kinase to preserve cellular energy and promote repair, as well as directly reducing inflammation and enhancing microcirculation.

How Food Choices Impact on Male Fertility.

PURPOSE OF REVIEW: Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting an association between nutrition and male fertility. Here, we have highlighted the impact of the various food groups on reproductive hormones and on spermatogenesis, and the effects of classical and latest dietary patterns such as Mediterranean diet, Western diet, intermittent fasting, ketogenic diet, and vegan/vegetarian diet on male fertility. RECENT FINDINGS: Nutrients are the precursors of molecules involved in various body's reactions; therefore, their balance is essential to ensure the correct regulation of different systems including the endocrine system. Hormones are strongly influenced by the nutritional status of the individual, and their alteration can lead to dysfunctions or diseases like infertility. In addition, nutrients affect sperm production and spermatogenesis, controlling sexual development, and maintaining secondary sexual characteristics and behaviors. The consumption of fruit, vegetables, fish, processed meats, dairy products, sugars, alcohol, and caffeine importantly impact on male fertility. Among dietary patterns, the Mediterranean diet and the Western diet are most strongly associated with the quality of semen. Nutrients, dietary patterns, and hormonal levels have an impact on male infertility. Therefore, understanding how these factors interact with each other is important for strategies to improve male fertility.

The interplay between macronutrients and sleep: focus on circadian and homeostatic processes.

Sleep disturbances are an emerging risk factor for metabolic diseases, for which the burden is particularly worrying worldwide. The importance of sleep for metabolic health is being increasingly recognized, and not only the amount of sleep plays an important role, but also its quality. In this review, we studied the evidence in the literature on macronutrients and their influence on sleep, focusing on the mechanisms that may lay behind this interaction. In particular, we focused on the effects of macronutrients on circadian and homeostatic processes of sleep in preclinical models, and reviewed the evidence of clinical studies in humans. Given the importance of sleep for health, and the role of circadian biology in healthy sleep, it is important to understand how macronutrients regulate circadian clocks and sleep homeostasis.

Weight Loss and Sleep, Current Evidence in Animal Models and Humans.

Sleep is a vital process essential for survival. The trend of reduction in the time dedicated to sleep has increased in industrialized countries, together with the dramatic increase in the prevalence of obesity and diabetes. Short sleep may increase the risk of obesity, diabetes and cardiovascular disease, and on the other hand, obesity is associated with sleep disorders, such as obstructive apnea disease, insomnia and excessive daytime sleepiness. Sleep and metabolic disorders are linked; therefore, identifying the physiological and molecular pathways involved in sleep regulation and metabolic homeostasis can play a major role in ameliorating the metabolic health of the individual. Approaches aimed at reducing body weight could provide benefits for both cardiometabolic risk and sleep quality, which indirectly, in turn, may determine an amelioration of the cardiometabolic phenotype of individuals. We revised the literature on weight loss and sleep, focusing on the mechanisms and the molecules that may subtend this relationship in humans as in animal models.

Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans.

Biliverdin reductase-A (BVRA) is involved in the regulation of insulin signaling and the maintenance of glucose homeostasis. Previous research showed that BVRA alterations are associated with the aberrant activation of insulin signaling in dysmetabolic conditions. However, whether BVRA protein levels change dynamically within the cells in response to insulin and/or glucose remains an open question. To this aim, we evaluated changes of intracellular BVRA levels in peripheral blood mononuclear cells (PBMC) collected during the oral glucose tolerance test (OGTT) in a group of subjects with different levels of insulin sensitivity. Furthermore, we looked for significant correlations with clinical measures. Our data show that BVRA levels change dynamically during the OGTT in response to insulin, and greater BVRA variations occur in those subjects with lower insulin sensitivity. Changes of BVRA significantly correlate with indexes of increased insulin resistance and insulin secretion (HOMA-IR, HOMA-ß, and insulinogenic index). At the multivariate regression analysis, the insulinogenic index independently predicted increased BVRA area under curve (AUC) during the OGTT. This pilot study showed, for the first time, that intracellular BVRA protein levels change in response to insulin during OGTT and are greater in subjects with lower insulin sensitivity, supporting the role of BVR-A in the dynamic regulation of the insulin signaling pathway.

Obesity-Associated Hepatic Steatosis, Somatotropic Axis Impairment, and Ferritin Levels Are Strong Predictors of COVID-19 Severity.

The full spectrum of SARS-CoV-2-infected patients has not yet been defined. This study aimed to evaluate which parameters derived from CT, inflammatory, and hormonal markers could explain the clinical variability of COVID-19. We performed a retrospective study including SARS-CoV-2-infected patients hospitalized from March 2020 to May 2021 at the Umberto I Polyclinic of Rome. Patients were divided into four groups according to the degree of respiratory failure. Routine laboratory examinations, BMI, liver steatosis indices, liver CT attenuation, ferritin, and IGF-1 serum levels were assessed and correlated with severity. Analysis of variance between groups showed that patients with worse prognoses had higher BMI and ferritin levels, but lower liver density, albumin, GH, and IGF-1. ROC analysis confirmed the prognostic accuracy of IGF-1 in discriminating between patients who experienced death/severe respiratory failure and those who did not (AUC 0.688, CI: 0.587 to 0.789, p < 0.001). A multivariate analysis considering the degrees of severity of the disease as the dependent variable and ferritin, liver density, and the standard deviation score of IGF-1 as regressors showed that all three parameters were significant predictors. Ferritin, IGF-1, and liver steatosis account for the increased risk of poor prognosis in COVID-19 patients with obesity.

Nonalcoholic fatty liver disease and diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.

Growth Hormone Secretory Capacity Is Associated with Cardiac Morphology and Function in Overweight and Obese Patients: A Controlled, Cross-Sectional Study.

Obesity is associated with increased cardiovascular morbidity. Adult patients with growth hormone deficiency (GHD) show morpho-functional cardiological alterations. A total of 353 overweight/obese patients are enrolled in the period between 2009 and 2019 to assess the relationships between GH secretory capacity and the metabolic phenotype, cardiovascular risk factors, body composition and cardiac echocardiographic parameters. All patients underwent GHRH + arginine test to evaluate GH secretory capacity, DEXA for body composition assessment and transthoracic echocardiography. Blood samples are also collected for the evaluation of metabolic parameters. In total, 144 patients had GH deficiency and 209 patients had normal GH secretion. In comparing the two groups, we found significant differences in body fat distribution with predominantly visceral adipose tissue accumulation in GHD patients. Metabolic syndrome is more prevalent in the GHD group. In particular, fasting glycemia, triglycerides and systolic and diastolic blood pressure are found to be linearly correlated with GH secretory capacity. Epicardial fat thickness, E/A ratio and indexed ventricular mass are worse in the GHD group. In the population studied, metabolic phenotype, body composition, cardiovascular risk factors and cardiac morphology are found to be related to the GH secretory capacity. GH secretion in the obese patient seems to be an important determinant of metabolic health.

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity.

Sirtuin1 (SIRT1) and sclerostin play important roles in adipose tissue and bone metabolism. We evaluated the circulating SIRT1 and sclerostin relationship with mass and quality of bone while considering the degree of adiposity. Sixty-six premenopausal women (16 underweight, 25 normal weight and 25 with obesity), aged <50 years, were enrolled. Plasma SIRT1, sclerostin and DXA body composition (total fat mass (FM), abdominal visceral adipose tissue, lean mass, trabecular bone score (TBS) and lumbar spine and femoral neck (FN) bone mineral density (BMD)) were assessed. The patients with obesity showed the lowest SIRT1 and TBS values and the highest sclerostin concentrations; BMD increased with FM and BMI and had an inverse association with SIRT1. Sclerostin was negatively correlated with SIRT1 (ρ = −0.37, p = 0.002). When spine BMD, FN BMD and TBS were standardized for BMI, a positive correlation with SIRT1 and a negative correlation with sclerostin were seen (p < 0.005). In the regression analysis, sclerostin was the best independent, negative predictor for BMD and TBS, while SIRT1 directly predicted TBS (p < 0.05). In conclusion, blood measurement of SIRT1 and sclerostin could represent a snapshot of the bone status that, taking into account the degree of adiposity, may reduce the interference of confounding factors in the interpretation of bone health parameters.