Hyperinsulinemia-induced upregulation of adipocyte TPH2 contributes to peripheral serotonin production, metabolic dysfunction, and obesity.

Tryptophan hydroxylase (TPH) is a rate-limiting enzyme for serotonin or 5-hydroxytryptamine (5-HT) synthesis. Previously, adipocyte TPH1 has been linked to increased adipose 5-HT, reduced brown adipose tissue (BAT) thermogenesis, and obesity. However, the role of TPH2, a neural isoform highly expressed in obese adipose tissue, is unknown.

Optimizing measures of insulin-regulated lipolysis in humans.

The goals of these studies were to test for errors in measuring the insulin concentration resulting in 50% suppression from baseline free fatty acid palmitate rate of appearance (FFA IC) when measured with a two-step, euglycemic, hyperinsulinemic clamp (EHC). We also determined the reproducibility of FFA IC in weight-stable adults and assessed the magnitude of the change in FFA IC in response to weight loss. To accomplish this, we analyzed data from 46 studies of 27 volunteers enrolled in two ongoing clinical research studies that included weight loss by lifestyle intervention or bariatric surgery.

Human Adipose Tissue Metabolism in Obesity.

The scientific understanding of adipose tissue has advanced tremendously during the past decade. Once thought to be an inert fat storage organ, we now know that adipose tissue serves important functions in energy balance and endocrinology, as well as playing a central role in the development of metabolic diseases. Adipose tissue lipid storage and lipolysis are tightly controlled by hormones, such as insulin, in response to the body's energy needs.

Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans.

Adult males and females have markedly different body composition, and energy expenditure and have different degrees of risk for metabolic diseases. A major aspect of metabolic regulation involves the appropriate storage and disposal of glucose and fatty acids. The use of sophisticated calorimetry, tracer, and imaging techniques has provided insight into the complex metabolism of these substrates showing that the regulation of these processes varies tremendously throughout the day, from the overnight fasting condition to meal ingestion, to the effects of physical activity.

Clinical Utility of Serum C-Peptide Concentration for Hospitalized Patients with Hyperglycemia.

Serum C-peptide concentration is often utilized for diagnostic, prognostic, or therapeutic assessment in diabetes mellitus. However, there are limited clinical data regarding diagnostic and predictive value of C-peptide measured during hospitalizations for hyperglycemia. Adults admitted to Mayo Clinic inpatient facilities due to an acute hyperglycemic emergency between January 2017 and November 2022 were included in our study.

Changes in Endoscopic Activity and Classification of Lesions With Panenteric Capsule Endoscopy in Patients Treated for Crohn's Disease-A Prospective Blinded Comparison With Ileocolonoscopy, Fecal Calprotectin, and C-Reactive Protein.

Background And Aims: Panenteric capsule endoscopy (PCE) is a minimally invasive modality that may replace ileocolonoscopy (IC) in selected patients with Crohn's disease (CD). This study aimed to evaluate the dynamics of repeated assessment with PCE in patients receiving medical treatment for ileocolonic CD.

Methods: This prospective, blinded, multicenter study included patients with endoscopically active CD.

Dapagliflozin and Right Ventricular-Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown.

Objective: To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF.

Similar insulin regulation of splanchnic FFA and VLDL-TG in men with nonalcoholic hepatic steatosis and steatohepatitis.

This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis versus steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [H]palmitate and [C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions.

Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT).

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard.

Insulin regulation of regional lipolysis in upper-body obese and lean humans.

Background: Upper-body obesity (UBO) results in insulin resistance with regards to free fatty acid (FFA) release; how this differs by fat depot and sex between adults with UBO and lean adults is unknown. We tested the hypothesis that insulin suppression of FFA release from the splanchnic bed, leg fat, and upper-body nonsplanchnic (UBNS) adipose tissue would be impaired in UBO.

Methods: Fourteen volunteers with UBO (7 men and 7 women) and 14 healthy volunteers with normal weight (7 men and 7 women) participated in studies that included femoral artery, femoral vein, and hepatic vein catheterization.

Adipose Tissue Analysis Toolkit (ATAT) for automated analysis of adipocyte size and extracellular matrix in white adipose tissue.

Objective: The pathological expansion of white adipose tissue (WAT) in obesity involves adipocyte hypertrophy accompanied by expansion of the collagen-rich pericellular extracellular matrix (ECM) and development of crown-like structures (CLS). Traditionally, WAT morphology is assessed through immunohistochemical analysis of WAT sections. However, manual analysis of large histological sections is time-consuming, and the available digital tools for analyzing adipocyte size and pericellular ECM are limited.

Adipose Tissue Analysis Toolkit (ATAT) for Automated Analysis of Adipocyte Size and Extracellular Matrix in White Adipose Tissue.

Objective: The pathological expansion of white adipose tissue (WAT) in obesity involves adipocyte hypertrophy accompanied by expansion of collagen-rich pericellular extracellular matrix (ECM) and the development of crown-like structures (CLS). Traditionally, WAT morphology is assessed through immunohistochemical analysis of WAT sections. However, manual analysis of large histological sections is time-consuming, and available digital tools for analyzing adipocyte size and pericellular ECM are limited.

Characteristics of Normal Weight Insulin-Resistant Adults with Unfavorable Health Outcomes.

Insulin resistance can be present in otherwise healthy, normal weight adults. Whether there are phenotype/sex-differences between normal weight insulin-resistant (NWIR) and normal weight insulin-sensitive (NWIS) Caucasians and whether there are differences in adverse health outcomes are unknown. Our goal was to define phenotypes and intermediate-term health outcomes of NWIR versus NWIS Caucasian adults.

Additional information obtained from mucosal biopsies is limited after pan-enteric capsule endoscopy in patients with suspected Crohn's disease.

Pan-enteric capsule endoscopy (CE) is an emerging alternative to ileo-colonoscopy for diagnosing Crohn's disease (CD). However, CE does not offer the opportunity to take biopsies to support the diagnosis. This study examined the additional information obtained with mucosal biopsies and the feasibility of CE as a single diagnostic procedure.

Suppression of Endogenous Insulin Secretion by Euglycemic Hyperinsulinemia.

Context: The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated.

Objective: We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity.

Methods: Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations.

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction.

Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF).

Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF.