Maartje Geraedts was born on March 4th 1982 in Asselt, The Netherlands. She completed secondary school at the “ Bischoppelijk College Broekhin” in 1998. In the same year, she started her study medical microbiology at the Gilde Opleidingen (Blerick, The Netherlands), where she graduated in 2001. She started her study Biochemistry at the Hogeschool Arnhem en Nijmegen (Nijmegen, The Netherlands) in 2001, followed by the study Master of Molecular Life Science in 2004 at the same location, where she graduated in 2005. She did her master thesis entitled ‘Glycosaminoglycans in the diaphragm of COPD patients’ at the department of Pulmonary Diseases, Radboud Medical Center Nijmegen. In February 2006, Maartje started her PhD at the University of Maastricht, at the department of Human Biology. She studied the effects of dietary proteins on release of satiety hormones from gastrointestinal cells, under supervision of Prof. Wim H.M. Saris and Dr. Freddy J. Troost. The research performed in this period is described in this thesis. In 2009, she was awarded a 3th place ‘Foppe en Hoor’ young investigator award by the Netherlands Organisation of Scientific Research (NWO) for her work on the effects of intraduodenally administered pea protein on food intake in lean and obese subjects. Currently, Maartje is working as a post-doc at the department of Anatomy and Neurobiology, University of Maryland School of Medicine, USA.
Abstract: BACKGROUND/AIM: High protein diets are the most effective to stimulate cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) release; however, which proteins are the most potent is not known. Here, the effects of specific dietary proteins on intestinal CCK and GLP-1 release were examined. METHODS: Duodenal biopsies of 10 healthy male subjects and 10 male rats were taken and placed in an Ussing chamber system. The biopsies were exposed on the luminal side to buffer, egg protein, codfish protein, ovomucoid, pea protein, and wheat protein. After an exposure time of 2 h, samples were taken from the serosal side. RESULTS: Pea protein and wheat protein increased CCK and GLP-1 release in human duodenal tissue, while codfish protein only increased CCK release. No elevated levels of CCK and GLP-1 were found after exposure of rat tissue to different proteins. CONCLUSION: Pea and wheat protein are the most potent stimulators of CCK and GLP-1 release in human duodenal tissue, and may therefore be good dietary additives in weight management.
Abstract: Dietary modulation of the response of gut satiety hormones, which partly regulate food intake, provides a promising treatment for overweight and obesity. Gut-derived cell lines such as STC-1 are widely used to investigate these hormonal responses to nutrients. To date, no peptide-YY (PYY) secreting cell line has been identified. The aim of this study was to investigate whether STC-1 cells are able to secrete PYY and if so, whether dietary compounds can modulate PYY secretion. The effects of fatty acid types C4:0, C12:0, C14:0, C16:0, and C18:0 on PYY release were investigated by measuring PYY in the supernatant after 30, 60, 90, and 120 min of incubation, respectively, using RIA assays. The STC-1 cells were able to secrete PYY in a time-dependent manner. It was shown that after 30 min, C4:0, C12:0, C16:0, and C18:0 caused increased PYY levels compared to the control. At time points 60 and 90 min, C4:0 and C18:0 induced elevated PYY levels compared to the control. After 120 min, C4:0, C14:0, and C18:0 caused elevated levels compared to the control. We are the first to show that the STC-1 cells are also able to secrete PYY next to cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1). Addition of fatty acids resulted in increased levels of PYY, which is consistent with the literature describing human studies. We conclude that the STC-1 cell line provides an appropriate cell line for screening the effects of ingredients on the release of the satiety-related gut hormones CCK, GLP-1, and PYY.
Abstract: In the present study, phage display-derived antibodies were used to investigate the topology of glycosaminoglycan epitopes in the diaphragm of chronic obstructive pulmonary disease (COPD) and non-COPD patients. Furthermore, the potential physiological significance of changes in the occurrence of glycosaminoglycan epitopes in the diaphragm of COPD patients was studied by determining the overlap in epitope recognition of glycosaminoglycan antibodies and growth factors. Diaphragm cryosections from non-COPD (n = 5) and COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II; n = 9) were incubated with antibodies directed against heparan sulphate, chondroitin sulphate and dermatan sulphate epitopes. Antibodies were visualised immunofluorescently. In addition, interference of antibody and growth factor binding with heparan sulphate epitopes was tested. Specific glycosaminoglycan epitopes showed increased expression in the diaphragm of COPD patients, whereas other epitopes were decreased or unaffected. Interestingly, the anti-heparan sulphate antibody HS4C3, which is directed against a downregulated epitope, interfered with the binding of hepatocyte growth factor. Three patients with the most severe airway obstruction also demonstrated interference of heparan sulphate antibody A04B08 with hepatocyte growth factor binding. Results indicate changes in glycosaminoglycan composition in the diaphragm of patients with chronic obstructive pulmonary disease. This may affect cellular physiology via alterations in growth factor handling and might be related to reduced levels of contractile protein in the diaphragm of these patients.
Abstract: Hypoxia impairs skeletal muscle function, but the precise mechanisms are incompletely understood. In hypoxic rat diaphragm muscle, generation of peroxynitrite is elevated. Peroxynitrite and other reactive nitrogen species have been shown to impair contractility of skinned muscle fibers, reflecting contractile protein dysfunction. We hypothesized that hypoxia induces contractile protein dysfunction and that reactive nitrogen species are involved. In addition, we hypothesized that muscle reoxygenation reverses contractile protein dysfunction. In vitro contractility of rat soleus muscle bundles was studied after 30 min of hyperoxia (Po2 approximately 90 kPa), hypoxia (Po2 approximately 5 kPa), hypoxia + 30 microM N(G)-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor), hyperoxia + 30 microM L-NMMA, and hypoxia (30 min) + reoxygenation (15 min). One part of the muscle bundle was used for single fiber contractile measurements and the other part for nitrotyrosine detection. In skinned single fibers, maximal Ca2+-activated specific force (Fmax), fraction of strongly attached cross bridges (alphafs), rate constant of force redevelopment (ktr), and myofibrillar Ca2+ sensitivity were determined. Thirty minutes of hypoxia reduced muscle bundle contractility. In the hypoxic group, single fiber Fmax, alphafs, and ktr were significantly reduced compared with hyperoxic, L-NMMA, and reoxygenation groups. Myofibrillar Ca2+ sensitivity was not different between groups. Nitrotyrosine levels were increased in hypoxia compared with all other groups. We concluded that acute hypoxia induces dysfunction of skinned muscle fibers, reflecting contractile protein dysfunction. In addition, our data indicate that reactive nitrogen species play a role in hypoxia-induced contractile protein dysfunction. Reoxygenation of the muscle bundle partially restores bundle contractility but completely reverses contractile protein dysfunction.
Abstract: COPD is associated with an increased load on the diaphragm. Since chronic muscle loading results in changes in antioxidant capacity and formation of reactive oxygen and reactive nitrogen species, we hypothesized that COPD has a similar effect on the diaphragm, which is related to the severity of COPD. Catalase activity was determined spectrophotometrically. Levels of 4-hydroxy-2-nonenal (HNE)-protein adducts and 3-nitrotyrosine (NT) formation were measured using western blotting. Levels of malondialdehyde (MDA) were assessed by high-performance liquid chromatography. We found that catalase activity was approximately 89% higher in the diaphragm of severe COPD patients (FEV1 37+/-5% predicted) compared with non-COPD patients. MDA levels, a marker for lipid peroxidation, were significantly lower in the diaphragm of COPD patients compared with non-COPD patients, whereas the level of HNE-protein adducts was equal in both groups. NT formation was not different between groups. However, increasing hyperinflation and NT formation were inversely correlated. These results indicate that in COPD the diaphragm adapts to a higher work load by increasing catalase activity, resulting in a reduction in oxidative damage to lipids and tyrosine nitration of proteins.
Abstract: Introduction: Glycemic index (GI) and protein (Prot) regulate postprandial
insulin responses which may affect 24h glucose metabolism
and therefore substrate partitioning. This study investigated the
effects of different protein and GI diets on 24h insulin, glucose and
substrate partitioning.
Methods: Ten (BMI:22.5 ± 0.61kg/m2) healthy male subjects stayed
4x 36 hours in a respiration chamber. 24-hour interstitial glucose
profiles were measured with a continuous glucose monitoring system
(CGMS). All subjects randomly received four isoenergetic diets with
either a normal (15En%) dairy Prot low GI (NDP/LGI) diet, a high
(25En%) dairy Prot LGI (HDP/LGI) diet, a normal vegetable Prot
LGI (NVP/LGI) diet or a normal dairy Prot high GI (NDP/HGI)
diet.
Results: The HDP/LGI diet increased 24 hours and night protein
oxidation compared with the NDP/LGI diet (P < 0.000). Fat oxidation
(24 hours) decreased in the HDP/LGI diet compared with the
NDP/LGI diet (41.82 ± 5.37 g/d vs. 70.54 ± 6.84 g/d; P < 0.01). Fat
oxidation (24 hours) tended to be lower in the NDP/HGI diet compared
with the NDP/LGI diet (P = 0.052). Incremental area under
the curve (IAUC) of 24 hours plasma glucose decreased in the HDP/
LGI diet compared with the NDP/LGI diet (P < 0.01). Glucose levels
decreased after lunch and dinner with a NVP/LGI diet compared
with a NDP/LGI diet (P < 0.05).
Conclusion: There is no significant effect of the glycemic index on
24 hours insulin and glucose levels, although glucose levels showed a
higher rise and subsequently fall after a meal. Higher dairy or vegetable
protein diet only tends to
Abstract: Background: Human duodenal mucosa secretes increased levels of
satiety signals upon exposure to intact protein. However, after oral
protein ingestion, gastric digestion leaves little intact proteins to
enter the duodenum. This study investigated whether bypassing the
stomach, through intraduodenal administration, affects hormone
release and food-intake to a larger extent than orally administered
protein in both lean and obese subjects.
Methods: Ten lean [body mass index (BMI):23.0 ± 0.7 kg/m2] and
ten obese (BMI:33.4 ± 1.4 kg/m2) healthy male subjects were
included. All subjects randomly received either pea protein solutions
(250 mg/kg bodyweight in 0.4 mL/kg bodyweight of water) or placebo
(0.4 mL/kg bodyweight of water), either orally or intraduodenally
via a naso-duodenal tube. Appetite-profile, plasma GLP-1,
CCK, and PYY concentrations were determined over a 2h period.
After 2 hour, subjects received an ad-libitum meal and food-intake
was recorded.
Results: CCK levels were increased at 10(P < 0.02) and 20(P < 0.01)
minutes after intraduodenal protein administration (IPA), in obese
subjects, compared to lean subjects, but also compared to oral protein
administration (OPA)(P < 0.04). GLP-1 levels increased after
IPA in obese subjects after 90(P < 0.02) to 120(P < 0.01) minutes,
compared to OPA. Food-intake was reduced after IPA both in lean
and obese subjects (-168.9 ± 40 kcal (P < 0.01) and -298.2 ± 44 kcal
(P < 0.01), respectively), compared to placebo. Also, in obese subjects,
food-intake was decreased after IPA (-132.6 ± 42 kcal;
P < 0.01), compared to OPA.
Conclusions: Prevention of gastric proteolysis through bypassing the
stomach effectively reduces food intake, and seems to affect obese
subjects to a greater extent than lean subjects. Enteric coating of
intact protein supplements may be an effective dietary strategy in the
prevention/treatment of obesity.
