Eveline Gart

Bio: Eveline Gart is an academic researcher from Netherlands Organisation for Applied Scientific Research. The author has contributed to research in topics: Adipose tissue & Steatosis. The author has an hindex of 5, co-authored 7 publications receiving 1136 citations. Previous affiliations of Eveline Gart include Wageningen University and Research Centre.

Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD.

Abstract: Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples. Ldlr−/−.Leiden mice received one of three different energy-dense (ED)-diets (n = 15/group) for 15 weeks. All of the ED diets induced obesity and metabolic risk factors, altered short-chain fatty acids (SCFA), and increased gut permeability and NAFLD to various extents. ED diets reduced the diversity of high-abundant bacteria and increased the diversity of low-abundant bacteria in all of the gut compartments. The ED groups showed highly variable, partially overlapping microbiota compositions that differed significantly from chow. Correlation analyses demonstrated that (1) specific groups of bacteria correlate with metabolic risk factors, organ dysfunction, and NAFLD endpoints, (2) colon mucosa had greater predictive value than other compartments, (3) correlating bacteria differed per compartment, and (4) some bacteria correlated with plasma SCFA levels. In conclusion, this comprehensive microbiota analysis demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.

Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis.

Abstract: Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr -/-.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (-17%) and hepatic steatosis (-22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.

Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr-/- .Leiden mice.

Abstract: The obesity epidemic increases the interest to elucidate impact of short‐chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr−/−.Leiden mice. Ldlr−/−.Leiden mice received 16 weeks either a high‐fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD‐fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD‐control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD‐induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1‐positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD‐induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD‐induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.The obesity epidemic increases the interest to elucidate impact of short‐chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr−/−.Leiden mice. Ldlr−/−.Leiden mice received 16 weeks either a high‐fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD‐fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD‐control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD‐induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1‐positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD‐induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD‐induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.

Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice

Abstract: Background: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. Methods: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. Results: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. Conclusions: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.

The role of adipose tissue in cardiovascular health and disease

Abstract: Accumulating knowledge on the biology and function of the adipose tissue has led to a major shift in our understanding of its role in health and disease. The adipose tissue is now recognized as a crucial regulator of cardiovascular health, mediated by the secretion of several bioactive products, including adipocytokines, microvesicles and gaseous messengers, with a wide range of endocrine and paracrine effects on the cardiovascular system. The adipose tissue function and secretome are tightly controlled by complex homeostatic mechanisms and local cell-cell interactions, which can become dysregulated in obesity. Systemic or local inflammation and insulin resistance lead to a shift in the adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the adipose tissue and the cardiovascular system is bidirectional, with vascular-derived and heart-derived signals directly affecting adipose tissue biology. In this Review, we summarize the current knowledge of the biology and regional variability of adipose tissue in humans, deciphering the complex molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system, and their possible clinical translation. In addition, we highlight the latest developments in adipose tissue imaging for cardiovascular risk stratification and discuss how therapeutic targeting of the adipose tissue can improve prevention and treatment of cardiovascular disease.

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology.

Abstract: The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

The central role of DNA damage in the ageing process

Abstract: Ageing is a complex, multifaceted process leading to widespread functional decline that affects every organ and tissue, but it remains unknown whether ageing has a unifying causal mechanism or is grounded in multiple sources. Phenotypically, the ageing process is associated with a wide variety of features at the molecular, cellular and physiological level—for example, genomic and epigenomic alterations, loss of proteostasis, declining overall cellular and subcellular function and deregulation of signalling systems. However, the relative importance, mechanistic interrelationships and hierarchical order of these features of ageing have not been clarified. Here we synthesize accumulating evidence that DNA damage affects most, if not all, aspects of the ageing phenotype, making it a potentially unifying cause of ageing. Targeting DNA damage and its mechanistic links with the ageing phenotype will provide a logical rationale for developing unified interventions to counteract age-related dysfunction and disease. This Review examines the evidence showing that DNA damage is associated with ageing phenotypes, suggesting that it may have a central role as the cause of ageing.

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions.

Abstract: The antibiotic crisis has led to a pressing need for alternatives such as antimicrobial peptides (AMPs). Recent work has shown that these molecules have great potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, anti-cancer agents and anti-inflammatories. A better understanding of the mechanism of action (MOA) of AMPs is an important part of the discovery of more potent and less toxic AMPs. Many models and techniques have been utilized to describe the MOA. This review will examine how biological assays and biophysical methods can be utilized in the context of the specific antibacterial and antibiofilm functions of AMPs.

Brown adipose tissue energy metabolism in humans

Abstract: The demonstration of metabolically active brown adipose tissue (BAT) in humans primarily using positron emission tomography coupled to computed tomography (PET/CT) with the glucose tracer 18-fluorodeoxyglucose (18FDG) has renewed the interest of the scientific and medical community in the possible role of BAT as a target for the prevention and treatment of obesity and type 2 diabetes (T2D). Here, we offer a comprehensive review of BAT energy metabolism in humans. Considerable advances in methods to measure BAT energy metabolism, including nonesterified fatty acids (NEFA), chylomicron-triglycerides (TG), oxygen, Krebs cycle rate, and intracellular TG have led to very good quantification of energy substrate metabolism per volume of active BAT in vivo. These studies have also shown that intracellular TG are likely the primary energy source of BAT upon activation by cold. Current estimates of BAT's contribution to energy expenditure range at the lower end of what would be potentially clinically relevant if chronically sustained. Yet, 18FDG PET/CT remains the gold-standard defining method to quantify total BAT volume of activity, used to calculate BAT's total energy expenditure. Unfortunately, BAT glucose metabolism better reflects BAT's insulin sensitivity and blood flow. It is now clear that most glucose taken up by BAT does not fuel mitochondrial oxidative metabolism and that BAT glucose uptake can therefore be disconnected from thermogenesis. Furthermore, BAT thermogenesis is efficiently recruited upon repeated cold exposure, doubling to tripling its total oxidative capacity, with reciprocal reduction of muscle thermogenesis. Recent data suggest that total BAT volume may be much larger than the typically observed 50-150 ml with 18FDG PET/CT. Therefore, the current estimates of total BAT thermogenesis, largely relying on total BAT volume using 18FDG PET/CT, may underestimate the true contribution of BAT to total energy expenditure. Quantification of the contribution of BAT to energy expenditure begs for the development of more integrated whole body in vivo methods.