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After the festive season, many people have become a member of the mighty fat army
.
It is well known that obesity is an energy imbalance caused by chronic caloric intake exceeding energy expenditure
.
"Five people walk, there must be two fat people" is the current status of the global population, and it is expected to further develop into a "four people walk, there must be two fat people" situation
.
Obesity has been shown to be strongly associated with diseases such as metabolic syndrome, cardiovascular disease, type 2 diabetes and nonalcoholic steatohepatitis
.
Therefore, avoiding obesity has always been the main theme of healthy living in the past, present and future
.
Intermittent fasting and calorie-restricted diets have been extensively studied in mice and humans as an effective therapy for obesity and its complications, it can help reduce weight, treat nonalcoholic fatty liver disease (NAFLD), dyslipidemia and insulin resistance, and even prolong life in animals
.
However, in the real world, unless it's a last resort (fat to the point of being sick and hospitalized), this eating strategy usually requires a lot of willpower and self-discipline (though generally self-disciplined people are unlikely to be fat)
.
Therefore, for most people, it is a major challenge to "keep your mouth shut" in daily life for a long time
.
In a new study published today in Cell Reports Medicine, a team led by Washington University in St.
Louis showed in mice that an experimental anticancer drug that deprives tumors of energy can also play a role in fasting.
benefits, resulting in reduced animal body weight and improved metabolic health
.
The research team previously found that hepatocyte responses to glucose deprivation are sufficient to mimic several key therapeutic effects of intermittent fasting and calorie-restricted diets on hepatic steatosis, hepatic inflammation, and insulin resistance, in part by inducing hepatocyte autophagic flux and secretion of antidiabetic fibroblast growth factor 21 (FGF21)
.
Since hepatocyte glucose transport and its downstream pathways are amenable to drug treatment, the team set out to investigate the possibility of using this pathway to combat metabolic diseases
.
L-arginine is a non-essential amino acid for the body, but it is a key source of energy for cancer cells
.
The experimental anti-liver cancer drug ADI-PEG 20 (polyethylene glycol-modified arginine deiminase) is being investigated as a potential treatment for a variety of cancers, including sarcomas, breast and pancreatic cancers, in addition to liver cancer
.
ADI-PEG 20 breaks down arginine in the blood, thereby depriving cancer cells of this critical energy source
.
The genes responsible for breaking down arginine are dramatically up-regulated when the body is fasted, so they wondered if ADI-PEG 20 could mimic the effects of fasting
.
The researchers administered ADI-PEG 20 to a group of genetically obese mouse models and a group of high-fat and high-sugar diet-induced obese mice, respectively
.
After administration, ADI-PEG 20 appeared to mimic some of the metabolic and therapeutic effects of fasting
.
The drug increased insulin sensitivity in animals, improved cholesterol levels, reduced liver fat accumulation and lowered inflammation
.
In genetically obese mice, the administered group lost about 25 percent more body weight than the control group
.
The drug's weight-loss effect was also observed in high-fat and high-sugar diet-induced obese mice
.
The researchers found that ADI-PEG 20 prompted cells to undergo autophagy, a clean-up process at the cellular level
.
Cells undergoing autophagy burn their own cellular waste for energy
.
During fasting, when there is no exogenous new energy, cells turn to autophagy to obtain their energy supply from within
.
In addition, the researchers do not believe that the drug's metabolic advantage comes from weight changes
.
By measuring a range of indicators, they found that significant changes in metabolism preceded weight changes
.
These data thus led to the hypothesis that increased arginine catabolism could modulate the host's arginine status to therapeutically direct energy metabolism
.
In conclusion, this study demonstrates that systemic and hepatocyte-directed arginine deprivation is sufficient to induce an adaptive hepatocyte fasting-like response and introduces an off-the-shelf drug therapy that exploits this pathway
.
Currently, ADI-PEG 20 has been tested in clinical trials investigating its safety and efficacy in the treatment of a variety of tumors, including breast, prostate, pancreatic and liver cancers
.
In general, metabolic therapy has fewer side effects and is safer than chemotherapy, radiation therapy and even newer immunotherapies used to treat cancer
.
"We hope to conduct a clinical trial of the drug to see if it produces similar metabolic benefits and weight loss in people who are overweight or obese," said the study's corresponding author, Dr.
Brian DeBosch, associate professor of pediatrics
.
"
There is also the question of long-term use .
Is the drug safe
.
It's not a small molecule like a statin that can be taken for decades
.
The drug is a protein, so patients may develop an immune response to it over time
.
Still, DeBosch sees potential for this treatment over a period of weeks to months
.
DeBosch adds: "Many obese patients who are considering bariatric surgery must lose weight first in order for the surgery to work.
" Safer
.
It is difficult for such patients to lose 10% of their body weight before surgery; this therapy may help patients lose weight before surgery, thereby reducing the risk of complications during and after surgery
.
"Paper link: https://doi.
org/10.
1016/j.
xcrm.
2021.
100498
.
It is well known that obesity is an energy imbalance caused by chronic caloric intake exceeding energy expenditure
.
"Five people walk, there must be two fat people" is the current status of the global population, and it is expected to further develop into a "four people walk, there must be two fat people" situation
.
Obesity has been shown to be strongly associated with diseases such as metabolic syndrome, cardiovascular disease, type 2 diabetes and nonalcoholic steatohepatitis
.
Therefore, avoiding obesity has always been the main theme of healthy living in the past, present and future
.
Intermittent fasting and calorie-restricted diets have been extensively studied in mice and humans as an effective therapy for obesity and its complications, it can help reduce weight, treat nonalcoholic fatty liver disease (NAFLD), dyslipidemia and insulin resistance, and even prolong life in animals
.
However, in the real world, unless it's a last resort (fat to the point of being sick and hospitalized), this eating strategy usually requires a lot of willpower and self-discipline (though generally self-disciplined people are unlikely to be fat)
.
Therefore, for most people, it is a major challenge to "keep your mouth shut" in daily life for a long time
.
In a new study published today in Cell Reports Medicine, a team led by Washington University in St.
Louis showed in mice that an experimental anticancer drug that deprives tumors of energy can also play a role in fasting.
benefits, resulting in reduced animal body weight and improved metabolic health
.
The research team previously found that hepatocyte responses to glucose deprivation are sufficient to mimic several key therapeutic effects of intermittent fasting and calorie-restricted diets on hepatic steatosis, hepatic inflammation, and insulin resistance, in part by inducing hepatocyte autophagic flux and secretion of antidiabetic fibroblast growth factor 21 (FGF21)
.
Since hepatocyte glucose transport and its downstream pathways are amenable to drug treatment, the team set out to investigate the possibility of using this pathway to combat metabolic diseases
.
L-arginine is a non-essential amino acid for the body, but it is a key source of energy for cancer cells
.
The experimental anti-liver cancer drug ADI-PEG 20 (polyethylene glycol-modified arginine deiminase) is being investigated as a potential treatment for a variety of cancers, including sarcomas, breast and pancreatic cancers, in addition to liver cancer
.
ADI-PEG 20 breaks down arginine in the blood, thereby depriving cancer cells of this critical energy source
.
The genes responsible for breaking down arginine are dramatically up-regulated when the body is fasted, so they wondered if ADI-PEG 20 could mimic the effects of fasting
.
The researchers administered ADI-PEG 20 to a group of genetically obese mouse models and a group of high-fat and high-sugar diet-induced obese mice, respectively
.
After administration, ADI-PEG 20 appeared to mimic some of the metabolic and therapeutic effects of fasting
.
The drug increased insulin sensitivity in animals, improved cholesterol levels, reduced liver fat accumulation and lowered inflammation
.
In genetically obese mice, the administered group lost about 25 percent more body weight than the control group
.
The drug's weight-loss effect was also observed in high-fat and high-sugar diet-induced obese mice
.
The researchers found that ADI-PEG 20 prompted cells to undergo autophagy, a clean-up process at the cellular level
.
Cells undergoing autophagy burn their own cellular waste for energy
.
During fasting, when there is no exogenous new energy, cells turn to autophagy to obtain their energy supply from within
.
In addition, the researchers do not believe that the drug's metabolic advantage comes from weight changes
.
By measuring a range of indicators, they found that significant changes in metabolism preceded weight changes
.
These data thus led to the hypothesis that increased arginine catabolism could modulate the host's arginine status to therapeutically direct energy metabolism
.
In conclusion, this study demonstrates that systemic and hepatocyte-directed arginine deprivation is sufficient to induce an adaptive hepatocyte fasting-like response and introduces an off-the-shelf drug therapy that exploits this pathway
.
Currently, ADI-PEG 20 has been tested in clinical trials investigating its safety and efficacy in the treatment of a variety of tumors, including breast, prostate, pancreatic and liver cancers
.
In general, metabolic therapy has fewer side effects and is safer than chemotherapy, radiation therapy and even newer immunotherapies used to treat cancer
.
"We hope to conduct a clinical trial of the drug to see if it produces similar metabolic benefits and weight loss in people who are overweight or obese," said the study's corresponding author, Dr.
Brian DeBosch, associate professor of pediatrics
.
"
There is also the question of long-term use .
Is the drug safe
.
It's not a small molecule like a statin that can be taken for decades
.
The drug is a protein, so patients may develop an immune response to it over time
.
Still, DeBosch sees potential for this treatment over a period of weeks to months
.
DeBosch adds: "Many obese patients who are considering bariatric surgery must lose weight first in order for the surgery to work.
" Safer
.
It is difficult for such patients to lose 10% of their body weight before surgery; this therapy may help patients lose weight before surgery, thereby reducing the risk of complications during and after surgery
.
"Paper link: https://doi.
org/10.
1016/j.
xcrm.
2021.
100498
