Overview:
The paper, “Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression” [11], studied the effect of different feeding patterns on hepatic (liver-related) gene transcription in mice, and provides the connection between time-restricted feeding (TRF) and the production of metabolic gene products in the liver. It is an essential part of the phosphorylation of CREB pathway, which highlights the close relationship between the circadian rhythm and several metabolic cycles.
Methods:
In this study’s experimental design, the feeding patterns of wild-type C57B6 mice (WT) and cryptochrome-deficient mice (cry1−/−;cry2−/−) were manipulated to analyze the changes in circadian/rhythmic gene expression within the liver. The cryptochrome protein plays an essential regulating role within the mammalian circadian clock, specifically within the SCN, which is further discussed in the phosphorylation of CREB pathway. Without this protein, the circadian oscillator is non-functional. Circadian oscillation is the “internal clock” that regulates biochemical pathways with solar time. Three different feeding patterns were administered to both WT and cryptochrome-deficient mice: ad libitum (unrestricted feeding), day-time restricted feeding, and prolonged fasting.
Results & Analysis:
The experimental results provided two main points that are important for the CREB pathway. The first takeaway is that TRF has the ability to restore feeding rhythms for organisms with a non-functioning circadian oscillator. More simply, organisms with a dysfunctional circadian clock can improve their regulation under an intermittent fasting regimen. Under TRF, cryptochrome-deficient mice exhibited the same levels of feeding rhythms as WT mice. This was determined through measuring the respiratory exchange ratio (RER), which is an important indicator of daily metabolic oscillations. RER peaked during the day and dropped drastically at night in both groups that followed a TRF regimen, showing the improvement of oscillation compared to groups on an ad libitum diet.
The second takeaway is that temporal feeding patterns can mediate metabolic regulators such as CREB, an inducer of gluconeogenesis in the fasted state. Under periods of fasting, results show that the number of genes regulated by CREB (CREB-targets) experienced increases in transcription only during periods of fasting for WT and cryptochrome-deficient mice under TRF. However, under ad libitum conditions, transcription levels of CREB targets were much more erratic and irregular, indicating much lower regulation of gene expression.
Significance & Connection to Type II Diabetes:
As mentioned above, this paper provides two main pieces of evidence that support glucose regulation via time-restricted feeding:
- Compared to an ad libitum diet, both WT and cryptochrome-deficient mice showed much greater circadian oscillation when following an intermittent fasting protocol.
- Compared to an ad libitum diet, both WT and cryptochrome-deficient mice showed much greater regulation in CREB phosphorylation upon times of fasting when following an intermittent fasting protocol.
Intermittent fasting provides tighter regulation on expression of genes controlled by the circadian clock, as well as the activation of CREB that stimulates gluconeogenesis in the liver. The unrestricted feeding patterns show little to no regulation of either of these pathways, leading to issues in glucose metabolism.
Individuals with type II diabetes have an irregular metabolic rhythm and over-expression of CREB targets, regardless of being in the fed or fasted state. Phosphorylation of CREB is over-activated in type II diabetic individuals, which constantly triggers gluconeogenesis to return glucose to the bloodstream. In summary, intermittent fasting, or TRF, allows for greater regulation of CREB targeted pathways like gluconeogenesis and glycogenolysis. Introducing periods of fasting helps sync the internal circadian clock with these genes, improving the regulation of glucose metabolism in type II diabetics.
This article summary page does a great job communicating the findings about circadian regulation of hepatic gene expression and its relevance to type II diabetes. I think your introduction would benefit from a more explicit statement regarding the specific role of hepatic gene expression in glucose metabolism and insulin sensitivity, especially for readers less familiar with the topic. Connecting the results to the significance for type II diabetes shows the implications for glucose metabolism and offers promising future research opportunities. I feel that brief conclusion summarizing the key takeaways and encouraging readers to explore further studies in the field would round off the webpage even better than it is now.
I love how the analysis of this paper is broken down into distinct sections: Overview, Methods, Results & Analysis, Significance & Connection to Type II Diabetes. This structure enables future readers interested in exploring the impact of intermittent fasting on Type II diabetes to quickly assess the paper’s relevance to their research. It allows them to efficiently extract key information without wasting any time. The adapted figures were also very well made, condensing crucial information from the paper into a more easily digestible format for the reader. The conclusion within the “Significance & Connection to Type II Diabetes” section also effectively wraps up the page and underscores the paper’s importance in addressing the initial question. Fantastic!
Great interpretation of this article! The “Significance & Connection to Type II Diabetes” section was extremely useful in crystallizing the “big picture” info, and the most important points to take away from this comprehensive study. Your explanation on why specifically cryptochrome-deficient mice were utilized, as the lack of the protein results in a compromised circadian rhythm, was very helpful in clearly establishing the effectiveness of intermittent/time-restricted fasting, in terms of oscillation restoration. One small change I would make would be to hyperlink your mentioning of “SCN” to the first chemical pathway since you mention it there, or briefly reiterate what it is/where it’s located.
Thank you Andy! I added a hyperlink to the pathway page when the SCN was mentioned. I agree that this would be a helpful connection to this page.
This page offers a great summary of the article. I feel the first results and analysis paragraph could have been explained better, and more info on the difference between wild-type ad libitum and time-restricted would have been helpful. I really appreciated the significance and connections section as a reiteration of results. This is another great article that seems very applicable to type II diabetes. Well done.
Another great page with clear description of the article and its relevance to the topic of the site.