Nicoleta Nan

SCOPE Interventions that boost NAD+ availability are of potential therapeutic interest for obesity treatment. The potential of nicotinamide (NAM), the amide form of vitamin B3 and a physiological precursor of NAD+, in preventing weight gain has not previously been studied in vivo. Other NAD+ precursors have been shown to decrease weight gain; however, their impact on adipose tissue was not addressed. METHODS AND RESULTS Two doses of NAM (high dose: 1%; and low dose: 0.25%) were given by drinking water to C57BL/6J male mice, starting at the same time as the high-fat diet feeding. NAM supplementation protected against diet-induced obesity by augmenting global body energy expenditure in C57BL/6J male mice. The manipulation markedly altered adipose morphology and metabolism, particularly in inguinal (i) white adipose tissue (iWAT). An increased number of brown and beige adipocyte clusters, protein abundance of UCP1, mitochondrial activity, adipose NAD+, and AMPK levels were observed in the iWAT of treated mice. Notably, a significant improvement in hepatic steatosis, inflammation and glucose tolerance was also observed in NAM high-dose treated mice. CONCLUSION NAM influences whole-body energy expenditure by driving changes in the adipose phenotype. Thus, NAM is an attractive potential treatment for preventing obesity and associated complications. This article is protected by copyright. All rights reserved.

Objectives: Several multivariate algorithms for preeclampsia (PE) screening in the first trimester have been developed over the past few years. These models include maternal factors, mean arterial pressure (MAP), uterine artery Doppler (UtA-PI), and biochemical markers (pregnancy-associated plasma protein-A (PAPP-A) or placental growth factor (PlGF)). Treatment with low-dose aspirin (LDA) has shown a reduction in the incidence of preterm PE in women with a high-risk assessment in the first trimester. An important barrier to the implementation of first-trimester screening is the cost of performing tests for biochemical markers in the whole population. Theoretical contingent strategies suggest that two-stage screening models could also achieve high detection rates for preterm PE with lower costs. However, no data derived from routine care settings are currently available. This study was conducted to validate and assess the performance of a first-trimester contingent screening process ...

The most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic varian...

Approximately 20% of type 1 diabetes (T1D) patients have an impaired awareness of hypoglyceamia (IAH). IAH represents a risk factor for severe and recurrent hypoglycaemic events, which can lead to brain damage. Because no effective treatments are currently available to prevent IAH in this population, characterising the set of brain alterations associated with IAH may reveal novel preclinical diagnostic or therapeutic strategies. Using state‐of‐the art neuroimaging techniques, we compared 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) uptake at rest between 10 T1D patients with IAH and nine patients with normal awareness of hypoglycaemia (NAH). T1D‐IAH patients showed a pattern of increased FDG‐PET uptake with respect to NAH patients (P < .05 corrected). Topographically, glucose metabolism was increased in the frontal and precuneus regions. Importantly, within the IAH group, this abnormal hypermetabolism correlated with IAH severity. This hypermetabolic state appear...

INTRODUCTION High Density Lipoproteins (HDL) are dysfunctional in hypercholesterolemia patients. The hypothesis was tested that nicotinamide (NAM) administration will influence HDL metabolism and reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT) in a murine model of hypercholesterolemia. METHODS Apolipoprotein E-deficient (KOE) mice were challenged with a high-fat diet for 4 weeks. The effect of different doses of NAM on cholesterol metabolism, and the ability of HDL to promote m-RCT was assessed. RESULTS The administration of NAM to KOE mice produced an increase (∼1.5-fold; P<0.05) in the plasma levels of cholesterol, which was mainly accounted for by the non-HDL fraction. NAM produced a [3H]-cholesterol plasma accumulation (∼1.5-fold) in the m-RCT setting. As revealed by kinetic analysis, the latter was mainly explained by an impaired clearance of circulating non-HDL (∼0.8-fold). The relative content of [3H]-tracer was lowered in the livers (...