A5010552977- Peroxisome Proliferator-Activated Receptors
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Glycogen Storage Diseases and Myoclonus
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Carbohydrate Chemistry and Synthesis
- Lysosomal Storage Disorders Research
- Cancer-related gene regulation
- Cannabis and Cannabinoid Research
- Cytokine Signaling Pathways and Interactions
- Microbial Metabolic Engineering and Bioproduction
- Rheumatoid Arthritis Research and Therapies
- Kruppel-like factors research
- Gut microbiota and health
- Polysaccharides Composition and Applications
- Neurological disorders and treatments
- Slime Mold and Myxomycetes Research
- Genetics, Aging, and Longevity in Model Organisms
- Autoimmune Neurological Disorders and Treatments
- Diet, Metabolism, and Disease
University of Groningen
2011-2023
University Medical Center Groningen
2011-2023
TiFN
2014-2015
Short-chain fatty acids (SCFAs) are the main products of dietary fiber fermentation and believed to drive fiber-related prevention metabolic syndrome. Here we show that SCFAs induce a peroxisome proliferator–activated receptor-γ (PPARγ)–dependent switch from lipid synthesis utilization. Dietary SCFA supplementation prevented reversed high-fat diet–induced abnormalities in mice by decreasing PPARγ expression activity. This increased mitochondrial uncoupling protein 2 raised AMP-to-ATP ratio,...
The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans rodents. major products of colonic fermentation fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against metabolic syndrome via a signaling cascade involves peroxisome proliferator-activated receptor (PPAR) γ repression AMP-activated protein kinase (AMPK) activation. In this study investigated...
Studies with dietary supplementation of various types fibers have shown beneficial effects on symptoms the metabolic syndrome. Short-chain fatty acids (SCFAs), main products intestinal bacterial fermentation fiber, been suggested to play a key role. Whether concentration SCFAs or their metabolism drives these is not yet clear. In this study we investigated SCFA concentrations and in vivo host uptake fluxes absence presence fiber guar gum. C57Bl/6J mice were fed high-fat diet supplemented 0%,...
Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases. To obtain insight into the network dynamics of fatty-acid β-oxidation, we constructed detailed computational model pathway subjected it to fat overload condition. The contains reversible saturable enzyme-kinetic equations experimentally determined parameters for rat-liver enzymes. It was validated by adding palmitoyl CoA or carnitine isolated mitochondria: without refitting measured parameters, correctly...
Glycogen storage disease (GSD) type 1a is an inborn error of metabolism caused by defective glucose-6-phosphatase catalytic subunit (G6PC) activity. Patients with GSD exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have shown that activity carbohydrate response element binding protein (ChREBP), a key regulator glycolysis de novo lipogenesis, increased 1a. In current study, we assessed contribution ChREBP nonalcoholic fatty liver (NAFLD)...
It is well established that, besides facilitating lipid absorption, bile acids act as signaling molecules that modulate glucose and metabolism. Bile acid metabolism, in turn, controlled by several nutrient‐sensitive transcription factors. Altered intrahepatic type 2 diabetes associates with perturbed synthesis. We aimed to characterize the regulatory role of primary intracellular metabolite glucose, glucose‐6‐phosphate (G6P), on Hepatic gene expression patterns composition were analyzed mice...
Defects in genes involved mitochondrial fatty-acid oxidation (mFAO) reduce the ability of patients to cope with metabolic challenges. mFAO enzymes accept multiple substrates different chain length, leading molecular competition among substrates. Here, we combined computational modeling quantitative mouse and patient data investigate whether substrate affects pathway robustness disorders. First, used comprehensive biochemical analyses wild-type mice deficient for medium-chain acyl-CoA...
Prevention of hypertriglyceridemia is one the biomedical targets in Glycogen Storage Disease type Ia (GSD Ia) patients, yet it unclear how hypoglycemia links to plasma triglyceride (TG) levels. We analyzed whole-body TG metabolism normoglycemic (fed) and hypoglycemic (fasted) hepatocyte-specific glucose-6-phosphatase deficient (L-G6pc-/- ) mice. De novo fatty acid synthesis contributed substantially hepatic accumulation L-G6pc-/- In conditions, enhanced adipose tissue lipolysis was main...
Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory drugs, but chronic use is hampered by metabolic side effects. Therefore, there an urgent medical need for improved GCs that as effective classical have a better safety profile. A well-established model to assess efficacy the collagen-induced arthritis (CIA) in mice, with features resembling rheumatoid arthritis. Models quantify undesired effects of on glucose kinetics less well-established. Recently, we described basal...
Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development obesity. In vitro studies indicate a regulatory role for cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant high fat diet-induced Whether this phenotype CB1-/- is related altered metabolism adipose tissue unknown.We evaluated differentiation/proliferation markers quantified lipogenic lipolytic activities tissues CB1+/+ fed high-fat (HF) or...
Diet and physical activity are thought to affect sustainable metabolic health survival.To improve understanding, we studied survival of mice feeding a low-fat (LF) or high-saturated fat/high sugar (HFS) diet, each with without free running wheel (RW) access.Additionally several endocrine indices were assessed at 6, 12, 18 24 months age.As expected, HFS left-shifted curve compared LF feeding, this was associated increased energy intake (visceral/total) adiposity, liver triglycerides, plasma...
Glycogen storage disease type Ia (GSDIa) is an inborn metabolic disorder characterized by impaired endogenous glucose production (EGP). Monitoring of patients with GSDIa prioritized because ongoing treatment developments. Stable isotope tracers may enable reliable EGP monitoring.
Abstract Background Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia characterized constitutive activation Carbohydrate Response Element Binding Protein (ChREBP), glucose-sensitive transcription factor. Previously, we showed that ChREBP limits non-alcoholic fatty (NAFLD) hepatic Ia. As has been proposed as...
Abstract Background Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia characterized constitutive activation Carbohydrate Response Element Binding Protein (ChREBP), glucose-sensitive transcription factor. Previously, we showed that ChREBP limits non-alcoholic fatty (NAFLD) hepatic Ia. As has been proposed as...
BACKGROUND: Lifelong consumption of a Western-style diet is risk factor for developing metabolic disorders and therefore impairs healthy aging. Dietary restriction (DR) could delay the onset age-related diseases prolong life span, however, extent to which this depends on type poorly understood. OBJECTIVE: To study whether feeding affects aging benefits DR. METHODS: Mice fed (ad libitum DR) were compared those standard DR). Survival several endocrine parameters analyzed. RESULTS: resulted in...
We investigated whether gases other than carbon dioxide are produced by N. crassa. A peak corresponding to ethylene has been detected using gas chromatography. Mass spectroscopy, however, indicated that the might be monoxide which, surprisingly, migrated with same chromatographic retention time as ethylene. Our results emphasize need for caution when interpreting based solely on data.