Simon N Dankel

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Verified

Simon verified their affiliation via an institutional email.

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• PhD
• Professor at University of Bergen

UbiA prenyltransferase domain containing 1 (Ubiad1) has the potential to affect cholesterol and phospholipid levels in different cell types. We previously identified Ubiad1 as a candidate gene for regulating subcutaneous fat pad weight in a mouse genome-wide association study. Here we evaluated the relationship between Ubiad1 and obesity-related tr...

Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative com...

Differentiating between an irrational versus a rational fear of hypoglycemia has treatment implications and presents significant challenge for clinicians facing patients with type 1 diabetes, illustrated in this case. A 39-year-old woman with autoimmune-positive insulin-dependent diabetes sought help to alleviate severe diabetes distress, and sympt...

Background and objective Metabolic associated fatty liver disease (MAFLD) is associated with abnormal lipid metabolism. Mitochondrial dysfunction is considered an important factor in the onset of MAFLD, whereas altered fatty acid composition has been linked to the severity of the disease. Tetradecylthioacetic acid (TTA), shown to induce mitochondri...

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analyzed 1928 patients with suspected stable angina pectoris (geometric mean age 61), repr...

Altered hepatic mitochondrial fatty acid β-oxidation and associated tricarboxylic acid (TCA) cycle activity contributes to lifestyle-related diseases, and circulating biomarkers reflecting these changes could have disease prognostic value. This study aimed to determine hepatic and systemic changes in TCA-cycle-related metabolites upon the selective...

Background IRX3 is implicated in genetic predisposition to obesity via the FTO variant locus. IRX3 shows FTO risk allele-dependent upregulation specifically during early adipogenesis, leading to a shift from energy-dissipation to fat storage in mature adipocytes. However, how changes in IRX3 expression at one developmental stage affect cellular phe...

We investigated whether adding gastropexy to sleeve gastrectomy (SG) reduced gastroesophageal reflux disease (GERD) in patients operated for severe obesity, assessed mainly by use of anti-reflux medication (ARM) and second operations due to GERD worsening. In a prospective non-randomized study, patients undergoing SG at two Norwegian hospitals were...

Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol...

Background Clinical studies on effects of marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) on lipoprotein-lipid components and glucose-insulin homeostasis have shown conflicting results, which may partly be...

Recent large-scale genomic association studies found evidence for a genetic link between increased risk of type 2 diabetes and decreased risk for adiposity-related traits, reminiscent of metabolically obese normal weight (MONW) association signatures. However, the target genes and cellular mechanisms driving such MONW associations remain to be iden...

Background: The valine (branched-chain amino acid) metabolite 3-hydroxyisobutyrate (3-HIB), produced by 3-Hydroxyisobutyryl-CoA Hydrolase (HIBCH), is associated with insulin resistance and type 2 diabetes, but implicated tissues and cellular mechanisms are poorly understood. We hypothesized that HIBCH and 3-HIB regulate hepatic lipid accumulation....

Proteoglycans are central components of the extracellular matrix (ECM) and binding partners for inflammatory chemokines. Morphological differences in the ECM and increased inflammation are prominent features of the white adipose tissues in patients with obesity. The impact of obesity and weight loss on the expression of specific proteoglycans in ad...

Context: The neutral amino acid transporter SLC7A10/ASC-1 is an adipocyte-expressed gene with reduced expression in insulin resistance and obesity. Inhibition of SLC7A10 in adipocytes was shown to increase lipid accumulation despite decreasing insulin-stimulated uptake of glucose, a key substrate for de novo lipogenesis. These data imply that alte...

Background: Ultra-processed foods (UPF) have become a staple of the diet in many countries, concomitant with increases in non-communicable diseases including cancer. Aim: The aim of this systematic literature review was to evaluate associations between the consumption of UPF and cancer risk. Methods: A systematic literature search for observat...

Background/Objectives Gastopexy (G) has been introduced as a surgical technique to reduce gastroesophageal reflux disease (GERD) in patients undergoing sleeve gastrectomy (SG). We aimed to determine whether adding G to SG improves use of acid reducing medication (ARM), second operations for GERD, epigastric pain or heartburn after surgery. Subjects...

Rest raw materials provide a new source of bioactive dietary ingredients, and this study aimed to determine the health effects of diets with chicken protein hydrolysate (CPH) and chicken oil (CO) generated from deboned chicken meat. Male Wistar rats (n = 56) were divided into seven groups in three predefined sub-experiments to study the effects of...

Background: Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. Objectives: To evaluated short- (3 mo) and long...

Background Excess adipose tissue is associated with increased cardiovascular and metabolic risk, but the volume of visceral and subcutaneous adipose tissue poses different metabolic risks. MRI with fat suppression can be used to accurately quantify adipose depots. We have developed a new semi-automatic method, RAdipoSeg, for MRI adipose tissue segm...

Obesity and type 2 diabetes increase morbidity and mortality via altered energy metabolism, associated with altered circulatory concentrations of amino acids and lipids as well as glucose. Concentrations of 3-hydroxyisobutyrate (3-HIB), a specific intermediary metabolite in the degradation of the branched-chain amino acid (BCAA) valine, show a stro...

Obesity, insulin resistance and type 2 diabetes represent major global health challenges, and a better mechanistic understanding of the altered metabolism in these conditions may give improved treatment strategies. SLC7A10, a member of the SLC7 subfamily of solute carriers, also named ASC-1 (alanine, serine, cysteine transporter-1), has recently be...

Background and aims Visceral adipose tissue (VAT) volume is associated with common lifestyle diseases. Dietary quality, including food matrix and degree of carbohydrate cellularity, as well as the carbohydrate/fat ratio, may influence VAT volume. We aimed to determine the effects of isocaloric diets differing in either “cellularity”, a novel marker...

Background Physical activity (PA) influences sympathetic stimulation, platelet activation as well as vascular function, and has been associated with improved health outcomes in patients with coronary heart disease. β-blocker therapy reduces sympathetic activity and improves platelet and endothelial function. We investigated if β-blocker treatment m...

Background/objectives There is limited long-term data comparing the outcomes of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) for severe obesity, both with respect to body weight, quality of life (QOL) and comorbidities. We aimed to determine 7-year trajectories of body mass index (BMI), QOL, obesity-related comorbidities, biomarkers...

Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-m...

Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn +/+ and Srgn -/- mic...

Objective The accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We previously reported that a genetic deficiency of the intracellular signaling adaptor TRAF5 (TNF [tumor necrosis factor] receptor–associated factor 5) accelerates atherosclerosis in mice by increasing inflammatory...

It is widely assumed that people with obesity have several common eating patterns, including breakfast-skipping (1), eating during the night (2) and high fast-food consumption (3). However, differences in individual meal and dietary patterns may be crucial to optimizing obesity treatment. Therefore, we investigated the inter-individual variation in...

Background Low-carbohydrate diets are suggested to exert metabolic benefits by reducing circulating triacylglycerol (TG) concentrations, possibly by enhancing mitochondrial activity. Objective We aimed to elucidate mechanisms by which dietary carbohydrate and fat differentially affect hepatic and circulating TG, and how these mechanisms relate to...

Background & Aims Marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower circulating levels of triacylglycerols (TAGs), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) may reduce cholesterol levels. Clinical studies on effects of these dietary or supplem...

Skeletal and glycemic traits have shared etiology, but the underlying genetic factors remain largely unknown. To identify genetic loci that may have pleiotropic effects, we studied Genome-wide association studies (GWASs) for bone mineral density and glycemic traits and identified a bivariate risk locus at 3q21. Using sequence and epigenetic modelin...

SFAs play the leading role in 1 of the greatest controversies in nutrition science. Relative to PUFAs, SFAs generally increase circulating concentrations of LDL cholesterol, a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the purpose of regulatory mechanisms that control the diet-induced lipoprotein cholesterol dynamics i...

Objective Discovery of specific markers that reflect altered hepatic fatty acid oxidation could help to detect an individual's risk of fatty liver, type 2 diabetes and cardiovascular disease at an early stage. Lipid and protein metabolism are intimately linked, but our understanding of this crosstalk remains limited. Methods In male Wistar rats, w...

Elucidation of mechanisms that govern lipid storage, oxidative stress and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter 1 (ASC-1), shows st...

Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SM...

Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. Here we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary...

White adipose tissue plays an important role in physiological homeostasis and metabolic disease. Different fat depots have distinct metabolic and inflammatory profiles and are differentially associated with disease risk. It is unclear whether these differences are intrinsic to the pre-differentiated stage. Using single-cell RNA sequencing, a unique...

Over the latest decades, there has been a rapid development of laboratory techniques used for analyzing the pathways from the genes to the final physiology of an organism. The study of all genes in an organism is defined as genomics. In analog to this, studies of all the features along the path from the genes to the final phenotype is called transc...

Objective: A causal obesity risk variant in the FTO locus was recently shown to inhibit adipocyte thermogenesis via increased adipose expression of the homeobox transcription factors IRX3 and IRX5. However, causal effects of IRX5 on fat storage remain to be shown in vivo, and discovery of downstream mediators may open new therapeutic avenues. Met...

Background: Inhibition of Irx3 and Irx5 has been shown to reduce body weight and white adipose tissue (WAT) mass through cell-autonomous and sympathetic-induced increases in adipocyte beiging and thermogenesis in mice and humans. However, the underlying mechanisms of the Irx control over beiging are still largely unknown, as illustrated by recent...

The objective of this study was to compare the biochemical changes related to glucose tolerance and lipid metabolism in non-diabetic patients shortly after vertical sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Non-diabetic women and men with morbid obesity were studied the day before and six days after SG (N = 15) or RYGB (N = 16). P...

Background: Adipose tissue plays a crucial role in diet- and obesity-related insulin resistance, with implications for several metabolic diseases. Identification of novel target genes and mechanisms that regulate adipocyte function could lead to improved treatment strategies. RND3 (RhoE/Rho8), a Rho-related GTP-binding protein that inhibits Rho ki...

OBJECTIVE Altered plasma amino acid levels have been implicated as markers of risk for incident type 2 diabetes; however, amino acids are also related to established diabetes risk factors. Therefore, potential confounding for and the impact from competing risks require evaluation. RESEARCH DESIGN AND METHODS We prospectively followed 2,519 individ...

Objective Accumulation of visceral white adipose tissue (WAT) associates with insulin resistance, adipose tissue inflammation, and metabolic syndrome, whereas accumulation of subcutaneous WAT may be protective. We aimed to identify molecular mechanisms that might provide mechanistic insights underlying the phenotypic differences in these tissues. M...

Studies have implicated the extracellular matrix (ECM) of adipose tissue in insulin resistance. The proteoglycan decorin, a component of ECM, has been associated with glucose tolerance, but possible causal effects on metabolism remain to be explored. We here sought to determine metabolic consequences of loss of decorin in mice (DcnKO). DcnKO mice w...

Supplementary Figure 6. Omapatrilat inhibits MME enzymatic activity. Immortalized human white preadipocytes were treated vehicle (DMSO) or Omapatrilat (1 μM) for 24 h before cell lysis. Cell lysis and MME activity measurements were performed with a MME activity assay kit. N = 3.

Background: Different aspects of dietary pattern, including macronutrient and food profiles, may affect visceral fat mass and metabolic syndrome. Objective: We hypothesized that consuming energy primarily from carbohydrate or fat in diets with similar food profiles would differentially affect the ability to reverse visceral adiposity and metabol...

Background: Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive. Methods: We examined epigenomic data, allelic activity, motif con...

Introduction: Tamoxifen is an anti-estrogen drug used in treatment of Estrogen Receptor (ER) positive breast cancer. Effects and side effects of tamoxifen is the sum of tamoxifen and all its metabolites. 4-Hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen) both have ER affinity exceeding that of the parent drug tamox...

ObjectiveCOL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration.MethodsCOL6A3 mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI-matched obese subjects resistant or sensitive to insulin (surgical whole tissue biop...

White, beige, and brown adipocytes are developmentally and functionally distinct but often occur mixed together within individual depots. To target white, beige, and brown adipocytes for diagnostic or therapeutic purposes, a better understanding of the cell surface properties of these cell types is essential. Using a combination of in silico, in vi...

Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative com...

Repeated attempts to lose weight by temporary dieting may result in weight cycling, eventually further gain of body fat, and possible metabolic adaptation. We tested this by a controlled experiment in C57BL/6J mice subjected to four weight cycles (WC), continuous hypercaloric feeding (HF), or low-fat feeding (LF). To search for genes involved in an...

Objectives: Increased intra-adipose cortisol is thought to promote obesity, but few human studies have investigated intra-adipose glucocorticoid hormones and none have demonstrated prospective changes with fat loss. Design and methods: Subcutaneous adipose tissue (SAT) was obtained from obese subjects before and 1-year after surgery-induced fat...

The p160/Steroid Receptor Coactivators SRC-1, SRC-2/GRIP1, and SRC-3/AIB1 are important regulators of Estrogen Receptor alpha (ERα) activity. However, whereas the functions of SRC-1 and SRC-3 in breast tumourigenesis have been extensively studied, little is known about the role of SRC-2. Previously, we reported that activation of the cAMP-dependent...

Upregulated differentially expressed genes induced by SRC-2 shRNA. FC ≥1.5, q-value = 0. (XLSX)

(DOC)

Primer sequences used for Q-rt-PCR. (DOC)

Overlapping downregulated differentially expressed genes induced by SRC-2 shRNA and cAMP. FC ≥1.3, q-value = 0. (XLSX)

Upregulated overlapping differentially expressed genes induced by SRC-2 shRNA and cAMP. FC ≥1.3, q-value = 0. (XLSX)

Downregulated differentially expressed genes induced by SRC-2 shRNA. FC ≥1.5, q-value = 0. (XLSX)

Downregulated differentially expressed genes induced by cAMP. FC ≥1.5, q-value = 0. (XLSX)

Upregulated differentially expressed genes induced by cAMP. FC ≥1.5, q-value = 0. (XLSX)

Correspondence analysis (CA) plot showing projection of microarray samples. Ctr shRNA: pink squares, SRC-2 shRNA: green diamonds, cAMP: purple circles. The first principle component is shown on the x-axis and the second principle component is displayed on the y-axis. All three groups of samples are separated along the first principle component (22....

Background: Adipose tissue is critical for systemic metabolic health. Identifying key factors regulating adipose tissue function is a research priority. The NR4A subfamily of nuclear receptors (NRs) (NR4A1/NUR77, NR4A2/NURR1 and NR4A3/NOR1) has emerged as important proteins in different disease states and in the regulation of metabolic tissues, pa...

Primary hyperparathyroidism (PHPT) is characterised by increased production of parathyroid hormone (PTH) resulting in elevated serum calcium levels. The influence on bone metabolism with altered bone resorption is the most studied clinical condition in PHPT. In addition to this, patients with PHPT are at increased risk of non-skeletal diseases, suc...

Primary hyperparathyroidism (PHPT) is characterised by increased production of parathyroid hormone (PTH). The most studied effect of PTH is its influence on calcium metabolism with an elevated concentration of serum calcium and altered bone resorption. In addition to this, patients with PHPT are at increased risk of non-skeletal diseases, such as i...

Breast cancer is the most frequent malignancy in women in the Western world. Hormone receptor positive breast cancers are managed with endocrine treatment in which the estrogen receptor (ER) is blocked using a selective estrogen receptor modulator (SERM) such as tamoxifen or by targeting the estrogen synthesis using aromatase inhibitors (AIs). Nucl...

Breast cancer is the most frequent malignancy in women in the Western world. Hormone receptor positive breast cancers are managed with endocrine treatment in which the estrogen receptor (ER) is blocked using a selective estrogen receptor modulator (SERM) such as tamoxifen or by targeting the estrogen synthesis using aromatase inhibitors (AIs). Nucl...

A better understanding of the molecular links between obesity and disease is potentially of great benefit for society. In this paper we discuss proposed mechanisms whereby bariatric surgery improves metabolic health, including acute effects on glucose metabolism and long-term effects on metabolic tissues (adipose tissue, skeletal muscle, and liver)...

Hepatocyte nuclear factor-4 alpha (HNF-4alpha) is a member of the nuclear receptor superfamily with important roles in hepatic metabolism. Fasting induces the cAMP/protein kinase A (PKA)-signaling pathway. The mechanisms whereby cAMP regulates HNF-4alpha transcriptional activity are incompletely understood. We have therefore investigated the role o...

Medication in 16 patients before and one year after bariatric surgery. (0.01 MB PDF)

Differentially expressed homeobox transcription factors in adipose tissue. (0.02 MB PDF)

Illumina microarray analysis of adipose tissue before versus one year after bariatric surgery. (7.15 MB XLS)

Down-regulated genes in adipose tissue after bariatric surgery that contain one or more binding sites for one or more homeobox transcription factors. (0.03 MB PDF)