Adderall 7.5mg

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The anti-inflammatory benefits of the 5:2 fasting diet are attributed to a pair of proteins.

A dietary approach involving five days of normal eating and two days of calorie restriction has been shown to safeguard against liver

inflammation without promoting weight gain, according to a new study that has pinpointed the specific proteins responsible for this beneficial outcome.

Globally, the most common chronic liver disorder is non-alcoholic fatty liver disease (NAFLD), which occurs when excess fat accumulates in the liver due to factors other than excessive alcohol consumption. This condition is often associated with genetic predisposition and excess body weight, and if left unaddressed, it can escalate into a more severe state known as NASH (non-alcoholic steatohepatitis), marked by liver inflammation and scarring. Moreover, NASH significantly elevates the risk of liver failure and liver cancer.

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Intermittent fasting Recently, intermittent fasting has become popular for its potential to enhance health, particularly liver health. A study conducted by researchers from the German Research Center (DKF and the University of Tübingen how intermittent fasting could impact liver disease

To trigger NASH, scientists put mice on a high-fat, high-sugar diet similar to a typical Western diet for 32 weeks. They then divided the mice into two groups: one continued to have unrestricted access to the unhealthy diet, while the other was put on an intermittent fasting plan, where they abstained from food for two non-consecutive days per week, but were allowed to drink water freely.

The mice that were able to eat unlimited food gained weight and body fat and experienced chronic liver inflammation, as anticipated. On the other hand, despite consuming more food on non-fasting days, the group that practiced intermittent fasting did not gain weight, exhibited fewer signs of liver disease, and had lower levels of biomarkers indicating liver damage.

 

The researchers determined that following a 5:2 diet made the mice resistant to developing NASH. By varying the duration and frequency of fasting periods, the researchers discovered that a 5:2 regimen was more effective than a 6:1 regimen, and fasting for 24 hours was more beneficial than fasting for 12 hours.

 

By analyzing the protein makeup, biochemical processes, and gene expression in the livers of mice that were either fasting or not, researchers discovered two key proteins involved in the liver’s protective response to fasting: PPAR-alpha and PCK1.

 

PPAR-alpha plays a crucial role in controlling fat metabolism in the liver and is essential for ketogenesis, which is the process of breaking down fatty acids to generate ketone bodies in response to extended periods of fasting. On the other hand, PCK1 is an enzyme that governs the production of glucose from specific carbon sources other than carbohydrates, a process known as gluconeogenesis.

Analysis of the liver’s protein makeup, metabolic processes, and gene expression in mice that fasted versus those that didn’t revealed two key players in the liver’s protective response to fasting:

 

PPAR-alpha and PCK1. PPAR-alpha is a crucial controller of liver fat metabolism, essential for the production of ketone bodies from fatty acids, a vital adaptation to extended fasting periods. Meanwhile, PCK1 is an enzyme that oversees the creation of glucose from non-carbohydrate sources, a process known as gluconeogenesis.

 

“According to Heikenwälder, the alternating periods of fasting trigger significant metabolic shifts that collectively function as a natural cleansing process, ultimately aiding in the fight against MASH*.”

 

Intermittent fasting did not effectively prevent chronic inflammation or liver scarring in mice whose liver cells had PPAR-alpha and PCK1 genetically removed. Furthermore, reduced levels of these proteins were also found in tissue samples from humans with NASH.

 

Pemafibrate, a drug already available under the brand name Parmodia, acts similarly to PPAR-alpha in reducing triglyceride levels, which are a form of fat found in the bloodstream and can lead to the hardening or thickening of arteries when elevated.

In mouse studies, pemafibrate induced metabolic alterations resembling those observed in mice following the 5:2 diet, although it only partially replicated the protective benefits associated with fasting.

 

Heikenwälder expressed that it is not unexpected that pemafibrate can only impact one of the main players involved. He also mentioned that there is currently no drug that can replicate the actions of PCK1.

 

In addition to its weight loss benefits, the 5:2 intermittent fasting regimen also alleviated ongoing, chronic liver inflammation associated with non-alcoholic steatohepatitis (NASH).

Following an additional four-month period of intermittent fasting, mice that had developed NASH as a result of consuming a Western diet exhibited improved blood profiles, reduced liver fat accumulation, and diminished liver inflammation, ultimately leading to a lower incidence of liver cancer.

 

According to Heikenwälder, the findings suggest that 5:2 intermittent fasting holds significant promise for preventing MASH and liver cancer, as well as treating existing cases of chronic liver inflammation.

 

The encouraging results warrant further investigation in human subjects to determine if intermittent fasting can replicate its protective effects against chronic liver inflammation in patients, as it has in the mouse model.

MASH, which stands for metabolic dysfunction-associated steatohepatitis, is a term that is synonymous with NASH. The press release mentions MASH, but the published paper mentions NASH.

The study was published in the journal Cell Metabolism.

Source: DKFZ

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