Atrial natriuretic peptide and leptin interactions in healthy men

Introduction: Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo. Methods: Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial. Results: Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release. Discussion: The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559)

Atrial natriuretic peptide and leptin interactions in healthy men

INTRODUCTION: Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo. METHODS: Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial. RESULTS: Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release. DISCUSSION: The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559

Culture of intestinal biopsy specimens and stool culture for detection of bacterial enteropathogens in patients infected with human immunodeficiency virus. The Berlin Diarrhea/Wasting Syndrome Study Group

The diagnostic yields of stool cultures and biopsy specimens for the detection of enteric bacterial pathogens in 213 human immunodeficiency virus-infected patients were compared. Forty-five percent (19 of 42) of the pathogens were detected exclusively by stool culture, 2% (1 of 42) of the isolates were detected exclusively by culture of biopsy specimens, and 53% (22 of 42) were detected by both methods. Repeated stool cultures remain the most important means of diagnosing enteric bacterial pathogens, which were encountered in 20% (40 of 213) of all patients. The additional culture of biopsy specimens should be reserved for patients with suspected mycobacteriosis.</jats:p

Spironolactone is associated with reduced mitotane levels in adrenocortical carcinoma patients.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Mitotane, a derivative of the pesticide dichlorodiphenyltrichloroethane, has been used successfully as first line chemotherapy since the 1960s, if maintained within a narrow therapeutic window. Spironolactone (SPL) is frequently used to treat glucocorticoid excess-associated adverse effects such as severe hypokalemia. Although data of a previous case report indicate a link, valid data regarding SPL use and mitotane plasma concentrations in a human cohort are lacking.This retrospective analysis includes data from 54 mitotane-receiving ACC patients (14 co-administered with SPL) treated between January 2005 and April 2020 (20 male, mean age 54.1 ± 2.2 years). All available mitotane concentrations, treatment doses, tumor stage and evidence of hormone activity were collected. Primary outcomes included mitotane levels and concentration/dose ratios as well as time-in-range (TR) in patients with and without additional SPL treatment. The SPL group was characterized by higher glucocorticoid secretion. Other features such as tumor stage, size and anthropometrics were similar between groups. Interestingly, the SPL group had significantly lower mitotane levels despite higher doses. Mitotane TR was significantly reduced in the SPL group, as was time-in-range to progression. These data provide first evidence in a human cohort for potential SPL-mitotane interactions (beyond mentioned case report), which affect dose response and may modulate treatment outcomes. This should caution clinicians to carefully adjust mitotane doses during SPL treatment in ACC patients or choose alternative therapeutic options

Short-term variability of proton density fat fraction in pancreas and liver assessed by multiecho chemical-shift encoding-based MRI at 3&nbsp;T.

Background: Quantification of pancreatic fat (PF) and intrahepatic lipids (IHL) is of increasing interest in subjects at risk for metabolic diseases. There is limited data available on short- and medium-term variability of PF/IHL and on their dependence on nutritional status. Purpose: To assess short-term intraday variations of PF/IHL after a high-fat meal as well as medium-term changes after 5 days of high-caloric diet. Study Type: Prospective cohort study. Subjects: A total of 12 subjects (six males) for intraday variations study, 15 male subjects for medium-term high-caloric diet study and 11 age- and body mass index (BMI)-matched controls. Field Strength/Sequence: A 3 T; chemical-shift encoded multiecho gradient echo sequence. Assessment: For the intraday study, subjects were scanned after overnight fasting and after a high fat meal on the same day. For the medium-term study, 26 subjects were scanned after overnight fasting with 15/11 rescanned after 5 days of high-calorie diet/isocaloric diet. Proton density fat fraction (PDFF) maps were generated inline on the scanner. Regions of interest were manually drawn in head, body, and tail of pancreas and in the liver by a medical physicist and a doctoral student (26/4 years of experience). PF was calculated as the average of the head, body, and tail measurements. Statistical Tests: Repeated measurements ANOVA for assessing changes in PF/IHL, linear correlation analyses for assessing relationships of PF/IHL with BMI. Significance level P &lt; 0.05 for all. Results: Nonsignificant changes in PF (2.6 ± 1.0 vs. 2.7 ± 0.9% after high-fat meal, 1.4 ± 0.8 vs. 1.5 ± 0.6% [high-caloric diet] and 1.5 ± 0.8 vs. 1.8 ± 1.0% [isocaloric control group]), nonsignificant changes in IHL after high-fat meal (2.6 ± 1.3 vs. 2.5 ± 0.9%) and in the control group (1.1 ± 0.6 vs. 1.2 ± 1.1%), significantly increased IHL after high-caloric diet (1.7 ± 2.2% vs. 2.7 ± 3.6%). Nonsignificant changes in PF (2.6 ± 1.0 vs. 2.7 ± 0.9% after high-fat meal, 1.4 ± 0.8 vs. 1.5 ± 0.6% [high-caloric diet] and 1.5 ± 0.8 vs. 1.8 ± 1.0% [isocaloric control group]), nonsignificant changes in IHL after high-fat meal (2.6 ± 1.3 vs. 2.5 ± 0.9%) and in the control group (1.1 ± 0.6 vs. 1.2 ± 1.1%), significantly increased IHL after 5-days of high-caloric diet (1.7 ± 2.2% vs. 2.7 ± 3.6%). Data Conclusion: Time of day and nutritional status have no significant influence on PF/IHL and are therefore not likely to be major confounders in epidemiologic or clinical studies. Evidence Level: 2. Technical Efficacy: Stage 1

Incretin-responsive human pancreatic adipose tissue organoids: A functional model for fatty pancreas research

Objective: Infiltration of adipocytes into the pancreatic parenchyma has been linked to impaired insulin secretion in individuals with increased genetic risk of T2D and prediabetic conditions. However, the study of this ectopic fat depot has been limited by the lack of suitable in vitro models. Methods: Here, we developed a novel 3D model of functionally mature human pancreatic adipose tissue organoids by aggregating human pancreatic adipose tissue-derived stromal vascular fraction (SVF) cells into organoids and differentiating them over 19 days. Results: These organoids carry biological properties of the in situ pancreatic fat, presenting levels of adipogenic markers comparable to native pancreatic adipocytes and improved lipolytic and anti-lipolytic response compared to conventional 2D cultures. The organoids harbour a small population of immune cells, mimicking in vivo adipose environment. Furthermore, they express GIPR, allowing investigation of incretin effects in pancreatic fat. In accordance, GIP and the dual GLP1R/GIPR agonist tirzepatide stimulate lipolysis but had distinct effects on the expression of proinflammatory cytokines. Conclusions: This novel adipose organoid model is a valuable tool to study the metabolic impact of incretin signalling in pancreatic adipose tissue, revealing potential therapeutic targets of incretins beyond islets. The donor-specific metabolic memory of these organoids enables examination of the pancreatic fat-islet crosstalk in a donor-related metabolic context

Effects of caloric restriction on the gut microbiome are linked with immune senescence.

BACKGROUND: Caloric restriction can delay the development of metabolic diseases ranging from insulin resistance to type 2 diabetes and is linked to both changes in the composition and metabolic function of the gut microbiota and immunological consequences. However, the interaction between dietary intake, the microbiome, and the immune system remains poorly described. RESULTS: We transplanted the gut microbiota from an obese female before (AdLib) and after (CalRes) an 8-week very-low-calorie diet (800 kcal/day) into germ-free mice. We used 16S rRNA sequencing to evaluate taxa with differential abundance between the AdLib- and CalRes-microbiota recipients and single-cell multidimensional mass cytometry to define immune signatures in murine colon, liver, and spleen. Recipients of the CalRes sample exhibited overall higher alpha diversity and restructuring of the gut microbiota with decreased abundance of several microbial taxa (e.g., Clostridium ramosum, Hungatella hathewayi, Alistipi obesi). Transplantation of CalRes-microbiota into mice decreased their body fat accumulation and improved glucose tolerance compared to AdLib-microbiota recipients. Finally, the CalRes-associated microbiota reduced the levels of intestinal effector memory CD8+ T cells, intestinal memory B cells, and hepatic effector memory CD4+ and CD8+ T cells. CONCLUSION: Caloric restriction shapes the gut microbiome which can improve metabolic health and may induce a shift towards the naïve T and B cell compartment and, thus, delay immune senescence. Understanding the role of the gut microbiome as mediator of beneficial effects of low calorie diets on inflammation and metabolism may enhance the development of new therapeutic treatment options for metabolic diseases. TRIAL REGISTRATION: NCT01105143 , "Effects of negative energy balance on muscle mass regulation," registered 16 April 2010. Video Abstract