Key Proteins in Diet-Induced Thermogenesis
Diet weight loss is a commonly used weight loss model, such as caloric restriction (CR) and intermittent fasting (IF). Intermittent fasting can be divided into restricted time diet per day, 1:1 diet (one day of eating, one day of hunger), and 5:2 diet (5 days of eating, 2 days of hunger) and so on. Recent studies have found that intermittent light fasting can increase energy expenditure and improve obesity; clinical studies have also confirmed that this method can reduce the weight of obese people. Therefore, a comprehensive analysis of the molecular mechanism of IF inhibiting obesity has an important indication for the development of new weight-loss drugs. The interaction between the various organs of the body is essential to maintain the body's metabolic balance, and it is not clear whether the interaction between the organs plays a role in the weight loss of intermittent fasting.
Recently, the team of researcher Jin Wanzhu from the Institute of Zoology, Chinese Academy of Sciences and Huashan Hospital affiliated to Fudan University published a research paper Hepatokine pregnancy zone protein governs the diet-induced thermogenesis through activating brown adipose tissue in Advanced Science. The study screened diet-induced liver secretion proteins, and identified and verified that pregnancy zone protein (PZP) helps mice resist obesity caused by high-fat diet.
PZP is a liver-specific highly secreted protein and belongs to the α2M family of proteins. Previous studies have found that the abundance of the protein fluctuates greatly under conditions such as pregnancy and Alzheimer's, and its physiological function is not clear. Studies have shown that in mice and humans, the serum and liver PZP protein levels of obese individuals are lower than those of normal weight individuals; In the eating state, the PZP protein in serum and liver of mice and humans increased, suggesting that PZP protein may participate in the regulation of body metabolism after eating.
Researchers have found in the PZP protein function loss experiment that under normal high-fat diet conditions, PZP loss does not affect the weight of mice; Under the condition of high-fat diet combined with intermittent fasting, the lack of PZP caused a significant increase in the weight of the mice. PZP-deficient mice did not eat more or exercise less, but their body temperature and energy consumption after eating decreased. This suggests that the regulation of body weight by PZP has nothing to do with suppressing appetite and reducing exercise, but is related to promoting energy expenditure. As a secreted protein of the liver, what is the molecular mechanism of PZP to promote energy expenditure?
Brown fat is a special adipose tissue that produces heat and consumes energy. The UCP1 protein of this tissue can transport the high-energy protons produced by the decomposition of substances into the mitochondrial matrix, and then uncouple the energy conversion path of electron transfer and ATP synthesis to make chemical energy Released in the form of heat. Further research found that the abundance of UCP1 protein in PZP-deficient mice was significantly reduced, so their brown fat energy consumption was reduced, leading to weight gain. The results show that the PZP protein secreted by the liver can activate thermogenesis of BAT and play an important role in the weight loss induced by intermittent fasting.
In order to further analyze the molecular mechanism of PZP regulating energy metabolism, the research team co-expressed the BAT cDNA library and PZP protein in cells, combined with immunoprecipitation and protein profiling techniques, and identified the GRP78 protein in BAT as the receptor for PZP. GRP78 protein is an endoplasmic reticulum protein. Studies have found that in the IF state, the GRP78 protein in BAT specifically translocates to the cell membrane, binds to the PZP protein secreted from the liver, completes signal transduction across organs, and activates the p38 MAPK-ATF2 signaling pathway in BAT to promote UCP1 The expression of adipose tissue, thereby increasing the production of adipose tissue, reducing obesity and improving related metabolic disorders.
Under intermittent fasting conditions, administration of exogenous PZP protein can reduce the weight gain of wild-type mice, but has no effect on the weight of UCP1-deficient mice. It shows that the regulation of metabolism by PZP protein depends on the UCP1 protein, and suggests that under a certain metabolic state, supplementing exogenous PZP protein has the effect of reducing obesity. Injecting PZP protein into obese PZP-deficient mice can significantly reduce their body weight, while mice injected with control protein did not change their body weight even under the IF strategy. The study further showed that PZP protein has the effect of weight loss, suggesting that in the diet plan of intermittent fasting, one possible reason for the lack of weight loss in some people is that the abundance of PZP protein expression in this population is relatively low.
Studies have shown that under dietary induction, the PZP protein secreted by the liver can bind to the GRP78 receptor on brown adipose tissue, activate the p38 MAPK-ATF2-UCP1 signaling pathway to promote brown fat thermogenesis, improve obesity and related metabolic disorders, revealing The molecular mechanism of the interaction between the liver and brown fat under intermittent diet conditions provides an important basis for the prevention and treatment of obesity by regulating thermogenesis. It is expected to achieve clinical transformation and provide a new strategy for the treatment of weight loss.
At present, Wuxi Donglin Sci & Tech Development Co.,Ltd. has developed Elisa products related to PZP, If you want to know information about PZP Elisa kits, you can directly visit the website:
http://www.dldevelop.com/Research-reagent/dl-pzp-hu.html
Recently, the team of researcher Jin Wanzhu from the Institute of Zoology, Chinese Academy of Sciences and Huashan Hospital affiliated to Fudan University published a research paper Hepatokine pregnancy zone protein governs the diet-induced thermogenesis through activating brown adipose tissue in Advanced Science. The study screened diet-induced liver secretion proteins, and identified and verified that pregnancy zone protein (PZP) helps mice resist obesity caused by high-fat diet.
PZP is a liver-specific highly secreted protein and belongs to the α2M family of proteins. Previous studies have found that the abundance of the protein fluctuates greatly under conditions such as pregnancy and Alzheimer's, and its physiological function is not clear. Studies have shown that in mice and humans, the serum and liver PZP protein levels of obese individuals are lower than those of normal weight individuals; In the eating state, the PZP protein in serum and liver of mice and humans increased, suggesting that PZP protein may participate in the regulation of body metabolism after eating.
Researchers have found in the PZP protein function loss experiment that under normal high-fat diet conditions, PZP loss does not affect the weight of mice; Under the condition of high-fat diet combined with intermittent fasting, the lack of PZP caused a significant increase in the weight of the mice. PZP-deficient mice did not eat more or exercise less, but their body temperature and energy consumption after eating decreased. This suggests that the regulation of body weight by PZP has nothing to do with suppressing appetite and reducing exercise, but is related to promoting energy expenditure. As a secreted protein of the liver, what is the molecular mechanism of PZP to promote energy expenditure?
Brown fat is a special adipose tissue that produces heat and consumes energy. The UCP1 protein of this tissue can transport the high-energy protons produced by the decomposition of substances into the mitochondrial matrix, and then uncouple the energy conversion path of electron transfer and ATP synthesis to make chemical energy Released in the form of heat. Further research found that the abundance of UCP1 protein in PZP-deficient mice was significantly reduced, so their brown fat energy consumption was reduced, leading to weight gain. The results show that the PZP protein secreted by the liver can activate thermogenesis of BAT and play an important role in the weight loss induced by intermittent fasting.
In order to further analyze the molecular mechanism of PZP regulating energy metabolism, the research team co-expressed the BAT cDNA library and PZP protein in cells, combined with immunoprecipitation and protein profiling techniques, and identified the GRP78 protein in BAT as the receptor for PZP. GRP78 protein is an endoplasmic reticulum protein. Studies have found that in the IF state, the GRP78 protein in BAT specifically translocates to the cell membrane, binds to the PZP protein secreted from the liver, completes signal transduction across organs, and activates the p38 MAPK-ATF2 signaling pathway in BAT to promote UCP1 The expression of adipose tissue, thereby increasing the production of adipose tissue, reducing obesity and improving related metabolic disorders.
Under intermittent fasting conditions, administration of exogenous PZP protein can reduce the weight gain of wild-type mice, but has no effect on the weight of UCP1-deficient mice. It shows that the regulation of metabolism by PZP protein depends on the UCP1 protein, and suggests that under a certain metabolic state, supplementing exogenous PZP protein has the effect of reducing obesity. Injecting PZP protein into obese PZP-deficient mice can significantly reduce their body weight, while mice injected with control protein did not change their body weight even under the IF strategy. The study further showed that PZP protein has the effect of weight loss, suggesting that in the diet plan of intermittent fasting, one possible reason for the lack of weight loss in some people is that the abundance of PZP protein expression in this population is relatively low.
Studies have shown that under dietary induction, the PZP protein secreted by the liver can bind to the GRP78 receptor on brown adipose tissue, activate the p38 MAPK-ATF2-UCP1 signaling pathway to promote brown fat thermogenesis, improve obesity and related metabolic disorders, revealing The molecular mechanism of the interaction between the liver and brown fat under intermittent diet conditions provides an important basis for the prevention and treatment of obesity by regulating thermogenesis. It is expected to achieve clinical transformation and provide a new strategy for the treatment of weight loss.
At present, Wuxi Donglin Sci & Tech Development Co.,Ltd. has developed Elisa products related to PZP, If you want to know information about PZP Elisa kits, you can directly visit the website:
http://www.dldevelop.com/Research-reagent/dl-pzp-hu.html
