Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06621901
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-25
Brief Title:
Effect of Protein on Endoplasmic Reticulum Stress
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effect of High Protein Diet on Endoplasmic Reticulum Stress
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study was planned to provide information about the effect of short-term high protein diet HPD feeding on endoplasmic reticulum stress The definition of HPDs cannot be determined exactly They are defined differently by various scientific authorities However the target is for protein to be approximately 30 of total energy in HPD It has been determined that HPDs increase satiety thermogenesis and provide body weight loss and maintenance of loss In general there is evidence that HPDs provide more body weight loss in a short time compared to low protein diets It has been emphasized that the effect of high protein diet on weight loss is related to creating satiety thus reducing food intake and increasing thermogenesis However the physiological biochemical and molecular events that occur due to HPD feeding are not fully understood and the results have not been explained It has been determined that the effects of HPDs last between 1 and 6 days and 6 months The absence of any study in the literature on the short-term and long-term effects of HPD on oxidative events in humans reveals the original value of this study Therefore considering that long-term HPD feeding may increase the risk of cardiovascular disease blood pressure and blood lipid levels the effect of short-term HPD feeding on endoplasmic reticulum stress will be investigated in order to avoid these side effects Blood analyses planned for this prospective analytical study will be performed in GENKÖK Laboratory Healthy individuals will be administered 10 days of HPD and a 10-day normal diet as a control
Detailed Description:
Today many people are trying various nutritional modelsdiets to reduce body weight One of the most popular of these diets is the diets that reduce carbohydrate intake Western societies generally avoid high carbohydrate and fat intake For this reason interest in high protein intake in diets is increasing day by day Although there is no general consensus on what a high protein diet HPD is HPD applied for weight loss is a diet that contains approximately 30 of the energy provided by protein The World Health Organization WHO has defined obesity as an endemic public problem and stated that its prevalence is increasing With the increase in obesity individuals are trying various dietary changes to achieve weight loss These include diets with more regular macro and micronutrient patterns such as the Mediterranean Diet and DASH diet and diets that may cause deficiencies in terms of macro and micronutrients such as Atkins South Beach Zone and Stillman which contain high protein The most important reasons for the interest in HPD are that it causes rapid weight loss and provides a feeling of satiety This positive effect of HPDs on weight loss has attracted the attention of dietitians and has led them to increase the protein ratio in diets
It is known that HPDs provide more effective results in body weight loss compared to low-protein diets It is suggested that this effect occurs as a result of increased thermogenesis increased satiety and suppressed appetite and decreased glycemic index and glycemic load due to the replacement of refined carbohydrates with proteins In addition to this positive effect on weight loss HPD nutrition also has possible short- and long-term side effects Known complications of long-term HPD nutrition include increased risk of cardiovascular disease blood pressure blood lipids and renal dysfunction Cardiovascular problems in particular are a source of concern as they will eliminate the short-term positive effect of HPD on weight loss and increase the burden of cardiovascular disease in the long term Studies generally focus on HPD and weight loss there is limited data on the relationship between HPD nutrition and metabolic dysfunction such as endothelial dysfunction inflammatory markers antioxidant status and other chronic diseases The physiological biochemical and molecular events that occur due to high protein diets are not fully understood and their results have not been explained
High protein diets especially low carbohydrate diets are thought to have negative effects because they cause a decrease in fruit and vegetable consumption In those who eat HPD especially those with insufficient vitamins A C and E in their diets this will have a negative effect on antioxidant systems and will lead to the development of many chronic and metabolic diseases in the long term Despite the positive effects of HPD applied as a weight loss diet in the short term it is thought that the oxidative stress and inflammation it will create in the long term will cause an increase in chronic and metabolic diseases and comorbidities This increase in the disease burden will increase health expenditures both individually and socially
Increasing evidence has shown that ROS and inflammation increase the production of reactive oxygen species ROS There is a direct link between ROS production and cellular events such as protein oxidation and protein folding ROS and ROS production are integral components of ERS and are not merely consequences of ERS induction It has been reported that increased ERS triggers ERS and can cause various types of cell death First some forms of ROS can disrupt ER protein folding and trigger ERS Exogenous oxidants such as ROS producers peroxides metal ions and lipid oxidation products can activate some aspects of the UPR 7-ketocholesterol a major oxidation product of cholesterol in atherosclerotic plaque induces the UPR in macrophages and vascular smooth muscle cells The 7-ketocholesterol-activated UPR is suppressed by the antioxidant N-acetylcysteine indicating that ERS induction is dependent on ERS However other forms of ROS such as hydrophene peroxide H2O2 can only stimulate mild or specific components of the UPR A study has determined that selenocysteine-free phospholipid hydroperoxide GPx NPGPx a member of the glutathione peroxidase GPx family senses OS in the ER lumen and then forms a disulfide bond with GRP78 resulting in chaperone activity Furthermore OS induced during protein misfolding in the ER has led eukaryotic cells to develop antioxidative stress responses to restore cellular redox homeostasis The PERK branch of the UPR induces two transcription factors ATF4 and Nrf2 that transactivate antioxidative stress response genes including SODs HO-1 glutathione transferase and uncoupler mitochondrial protein 2 The PERK signaling pathway of the UPR acts to maintain redox balance during ERS through activation of ATF4 and Nrf2 Small molecular antioxidants such as butylated hydroxyanisole BHA can prevent ERS-induced apoptosis and promote proper protein folding and secretion suggesting a critical role for ERS in protein misfolding As another example two mitochondrial-targeted antioxidants Mitoquinone and MitoTempol have been shown to reduce mitochondrial ERS ERS and cell death in β cells Antioxidants can suppress both ERS and ERS Therefore treatments targeting both stressors may be effective in preventing both ERS and metabolic neurodegenerative immune and neoplastic diseases
Therefore the aim of this planned study is to examine the effect of HPD which has gained popularity especially with its increasing use in weight loss diets on ERS Thus scientific literature will be produced that can prevent the possible negative effects of HPD and at the same time it can support the reduction of ERS which is effective in the course of various chronic diseases
It is known that HPDs provide more effective results in body weight loss compared to low-protein diets It is suggested that this effect occurs as a result of increased thermogenesis increased satiety and suppressed appetite and decreased glycemic index and glycemic load due to the replacement of refined carbohydrates with proteins In addition to this positive effect on weight loss HPD nutrition also has possible short- and long-term side effects Known complications of long-term HPD nutrition include increased risk of cardiovascular disease blood pressure blood lipids and renal dysfunction Cardiovascular problems in particular are a source of concern as they will eliminate the short-term positive effect of HPD on weight loss and increase the burden of cardiovascular disease in the long term Studies generally focus on HPD and weight loss there is limited data on the relationship between HPD nutrition and metabolic dysfunction such as endothelial dysfunction inflammatory markers antioxidant status and other chronic diseases The physiological biochemical and molecular events that occur due to high protein diets are not fully understood and their results have not been explained
High protein diets especially low carbohydrate diets are thought to have negative effects because they cause a decrease in fruit and vegetable consumption In those who eat HPD especially those with insufficient vitamins A C and E in their diets this will have a negative effect on antioxidant systems and will lead to the development of many chronic and metabolic diseases in the long term Despite the positive effects of HPD applied as a weight loss diet in the short term it is thought that the oxidative stress and inflammation it will create in the long term will cause an increase in chronic and metabolic diseases and comorbidities This increase in the disease burden will increase health expenditures both individually and socially
Increasing evidence has shown that ROS and inflammation increase the production of reactive oxygen species ROS There is a direct link between ROS production and cellular events such as protein oxidation and protein folding ROS and ROS production are integral components of ERS and are not merely consequences of ERS induction It has been reported that increased ERS triggers ERS and can cause various types of cell death First some forms of ROS can disrupt ER protein folding and trigger ERS Exogenous oxidants such as ROS producers peroxides metal ions and lipid oxidation products can activate some aspects of the UPR 7-ketocholesterol a major oxidation product of cholesterol in atherosclerotic plaque induces the UPR in macrophages and vascular smooth muscle cells The 7-ketocholesterol-activated UPR is suppressed by the antioxidant N-acetylcysteine indicating that ERS induction is dependent on ERS However other forms of ROS such as hydrophene peroxide H2O2 can only stimulate mild or specific components of the UPR A study has determined that selenocysteine-free phospholipid hydroperoxide GPx NPGPx a member of the glutathione peroxidase GPx family senses OS in the ER lumen and then forms a disulfide bond with GRP78 resulting in chaperone activity Furthermore OS induced during protein misfolding in the ER has led eukaryotic cells to develop antioxidative stress responses to restore cellular redox homeostasis The PERK branch of the UPR induces two transcription factors ATF4 and Nrf2 that transactivate antioxidative stress response genes including SODs HO-1 glutathione transferase and uncoupler mitochondrial protein 2 The PERK signaling pathway of the UPR acts to maintain redox balance during ERS through activation of ATF4 and Nrf2 Small molecular antioxidants such as butylated hydroxyanisole BHA can prevent ERS-induced apoptosis and promote proper protein folding and secretion suggesting a critical role for ERS in protein misfolding As another example two mitochondrial-targeted antioxidants Mitoquinone and MitoTempol have been shown to reduce mitochondrial ERS ERS and cell death in β cells Antioxidants can suppress both ERS and ERS Therefore treatments targeting both stressors may be effective in preventing both ERS and metabolic neurodegenerative immune and neoplastic diseases
Therefore the aim of this planned study is to examine the effect of HPD which has gained popularity especially with its increasing use in weight loss diets on ERS Thus scientific literature will be produced that can prevent the possible negative effects of HPD and at the same time it can support the reduction of ERS which is effective in the course of various chronic diseases
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None