Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H.

The cannabinoid, cannabidiol (CBD), is part of the plant's natural defense system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy. Although there is no consensus on its precise mode of action as it affects many cellular targets, CBD does appear to influence mitochondrial function. This would suggest that there is a cross-kingdom ability to modulate stress resistance systems that enhance homeostasis.

Ethnic Differences in Body Fat Deposition and Liver Fat Content in Two UK-Based Cohorts.

Objective: Differences in the content and distribution of body fat and ectopic lipids may be responsible for ethnic variations in metabolic disease susceptibility. The aim of this study was to examine the ethnic distribution of body fat in two separate UK-based populations.

Methods: Anthropometry and body composition were assessed in two separate UK cohorts: the Hammersmith cohort and the UK Biobank, both comprising individuals of South Asian descent (SA), individuals of Afro-Caribbean descent (AC), and individuals of European descent (EUR).

Clinical and molecular evidence of accelerated ageing following very preterm birth.

Background: The mechanisms responsible for the associations between very preterm birth and a higher risk of poor cardiovascular and metabolic health in adult life are unknown.

Methods: Here, we compare the clinical and molecular phenotypes of healthy, normal-weight young adults (18-27 years), born very preterm (<33 weeks gestational age (GA)) and at full-term (37-42 weeks GA). Outcomes included whole-body MRI, hepatic and muscle H MRS, blood pressure measurements and telomere length.

Early preterm nutrition and the urinary metabolome in young adult life: follow-up of a randomised controlled trial.

Objective: We aimed to test the hypothesis that early diet programmes the metabolic profile of young adults born preterm.

Design: We analysed banked urine samples obtained at a 20-year follow-up visit from adults that had participated as neonates in controlled trials involving randomisation within 48 hours of birth to feeds of preterm formula (PTF), banked breast milk (BBM) or term formula (TF) for 1 month postnatally.

Main Outcome Measures: We performed proton nuclear magnetic resonance spectroscopy, analysing spectra by dietary group and sex.

Development of Early Adiposity in Infants of Mothers With Gestational Diabetes Mellitus.

Objective: Infants born to mothers with gestational diabetes mellitus (GDM) are at greater risk of later adverse metabolic health. We examined plausible candidate mediators, adipose tissue (AT) quantity and distribution and intrahepatocellular lipid (IHCL) content, comparing infants of mothers with GDM and without GDM (control group) over the first 3 postnatal months.

Research Design And Methods: We conducted a prospective longitudinal study using MRI and spectroscopy to quantify whole-body and regional AT volumes, and IHCL content, within 2 weeks and 8-12 weeks after birth.

The Search for Biomarkers of Long-Term Outcome after Preterm Birth.

Preterm birth and survival rates are rising globally, and consequently there is a growing necessity to safeguard life-long health. Epidemiological and other studies from around the world point to a higher risk of adverse adult health outcomes following preterm birth. These reports encompass morbidities in multiple domains, poorer reproductive health, and reduced longevity.

Effect of maternal body mass index on hormones in breast milk: a systematic review.

Background: Maternal Body Mass Index (BMI) is positively associated with infant obesity risk. Breast milk contains a number of hormones that may influence infant metabolism during the neonatal period; these may have additional downstream effects on infant appetite regulatory pathways, thereby influencing propensity towards obesity in later life.

Objective: To conduct a systematic review of studies examining the association between maternal BMI and the concentration of appetite-regulating hormones in breast milk.

Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study.

Background: The effect of mode of infant feeding on adiposity deposition is not fully understood.

Objective: The objective was to test the hypothesis that differences in total and regional adipose tissue content and intrahepatocellular lipid (IHCL) arise in early infancy between breast- and formula-fed infants and to describe longitudinal changes.

Design: This prospective longitudinal cohort study was performed in 2 hospitals in the United Kingdom.

Preterm birth and the metabolic syndrome in adult life: a systematic review and meta-analysis.

Background: Preterm birth is associated with features of the metabolic syndrome in later life. We performed a systematic review and meta-analysis of studies reporting markers of the metabolic syndrome in adults born preterm.

Methods: Reports of metabolic syndrome-associated features in adults (≥18 years of age) born at <37-week gestational age and at term (37- to 42-week gestational age) were included.

Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment.

Obesity has become a major global health problem. Recently, attention has focused on the benefits of fermentable carbohydrates on modulating metabolism. Here, we take a system approach to investigate the physiological effects of supplementation with oligofructose-enriched inulin (In).

Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis.

Background: Early-life nutrition may influence later body composition. The effect of breastfeeding and formula feeding on infant body composition is uncertain.

Objective: We conducted a systematic review and meta-analysis of studies that examined body composition in healthy, term infants in relation to breastfeeding or formula feeding.

Manganese enhancement in non-CNS organs.

Manganese-enhanced magnetic resonance imaging (MEMRI) is a novel imaging technique capable of monitoring calcium influx, in vivo. Manganese (Mn2+) ions, similar to calcium ions (Ca2+), are taken up by activated cells where their paramagnetic properties afford signal enhancement in T(1)-weighted MRI methodologies. In this study we have assessed Mn2+ distribution in mice using magnetization-prepared rapid gradient echo (MP-RAGE) based MRI, by measuring changes in T(1)-effective relaxation times (T(1)-eff), effective R(1)-relaxation rates (R(1)-eff) and signal intensity (SI) profiles over time.

A kisspeptin-10 analog with greater in vivo bioactivity than kisspeptin-10.

The kisspeptins are neuropeptides that stimulate the hypothalamo-pituitary-gonadal (HPG) axis. The smallest endogenous kisspeptin, kisspeptin-10 (KP-10), binds to the receptor KISS1R with a similar affinity to the full-length peptide, kisspeptin-54 (KP-54), but is less effective in vivo, possibly because of increased enzymatic breakdown or clearance. The kisspeptin system may have therapeutic potential in the treatment of reproductive disorders and endocrine cancers.

Cerebral activation by fasting induces lactate accumulation in the hypothalamus.

Carbon-13 ((13)C) high-resolution magic angle spinning (HR-MAS) spectroscopy was used to investigate the neuroglial coupling mechanisms underlying appetite regulation in the brain of C57BL/6J mice metabolizing [1-(13)C]glucose. Control fed or overnight fasted mice received [1-(13)C]glucose (20 micromol/g intraperitoneally [i.p.

Differential patterns of neuronal activation in the brainstem and hypothalamus following peripheral injection of GLP-1, oxyntomodulin and lithium chloride in mice detected by manganese-enhanced magnetic resonance imaging (MEMRI).

We have used manganese-enhanced magnetic resonance imaging (MEMRI) to show distinct patterns of neuronal activation within the hypothalamus and brainstem of fasted mice in response to peripheral injection of the anorexigenic agents glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and lithium chloride. Administration of both GLP-1 and OXM resulted in a significant increase in signal intensity (SI) in the area postrema of fasted mice, reflecting an increase in neuronal activity within the brainstem. In the hypothalamus, GLP-1 administration induced a significant reduction in SI in the paraventricular nucleus and an increase in the ventromedial hypothalamic nucleus whereas OXM reduced SI in the arcuate and supraoptic nuclei of the hypothalamus.

Imaging appetite-regulating pathways in the central nervous system using manganese-enhanced magnetic resonance imaging.

The global increase in obesity has led to a redoubling of efforts directed at understanding the control of energy homeostasis. Insight into the mechanisms which govern appetite regulation is central to understanding the pathophysiology of obesity and the design of effective therapeutic interventions. Exploitation of hormonal satiety signals secreted by the gut requires greater insight into their interaction with central nervous system (CNS) circuits of appetite control.

PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones.

Peptide YY (PYY) is secreted postprandially from the endocrine L cells of the gastrointestinal tract. PYY(3-36), the major circulating form of the peptide, is thought to reduce food intake in humans and rodents via high-affinity binding to the autoinhibitory neuropeptide Y (NPY) receptor within the arcuate nucleus. We studied the effect of early light-phase injection of PYY(3-36) on food intake in mice fasted for 0, 6, 12, 18, 24, and 30 h and show that PYY(3-36) produces an acute anorexigenic effect regardless of the duration of fasting.

The temporal sequence of gut peptide CNS interactions tracked in vivo by magnetic resonance imaging.

Hormonal satiety signals secreted by the gut play a pivotal role in the physiological control of appetite. However, therapeutic exploitation of the gut-brain axis requires greater insight into the interaction of gut hormones with CNS circuits of appetite control. Using the manganese ion (Mn2+) as an activity-dependent magnetic resonance imaging (MRI) contrast agent, we showed an increase in signal intensity (SI) in key appetite-regulatory regions of the hypothalamus, including the arcuate, paraventricular, and ventromedial nuclei, after peripheral injection of the orexigenic peptide ghrelin.

Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging.

The anorexigenic gut hormones oxyntomodulin (OXM) and glucagon-like peptide-1 (GLP-1) are thought to physiologically regulate appetite and food intake. Using manganese-enhanced magnetic resonance imaging, we have shown distinct patterns of neuronal activation in the hypothalamus in response to intraperitoneal injections into fasted mice of 900 and 5400 nmol/kg OXM or 900 nmol/kg GLP-1. Administration of OXM at either dose resulted in a reduced rate of signal enhancement, reflecting a reduction in neuronal activity, in the arcuate, paraventricular, and supraoptic nuclei of the hypothalamus.

The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway.

The vagus nerve forms a neuro-anatomical link between the gastrointestinal tract and the brain. A number of gastrointestinal hormones, including cholecystokinin and ghrelin, require an intact vagal-brainstem-hypothalamic pathway to affect CNS feeding circuits. We have shown that the effects of peripheral administration of both peptide YY(3-36) (PYY(3-36)) and glucagon-like peptide-1 (GLP-1) on food intake and activation of hypothalamic arcuate feeding neurones are abolished following either bilateral sub-diaphragmatic total truncal vagotomy or brainstem-hypothalamic pathway transectioning in rodents.