- Not eating at regular times of the day increases food intake and increases the risk of obesity.
- A new study in mice suggests that increased weight gain from consuming food at inappropriate times results from impaired fat cells or thermogenesis, the process of burning calories to release heat. suggests that it is possible.
- Adipocytes exhibit rhythmic changes in thermogenic levels consistent with light-dark cycles, and discrepancies between these adipocyte cycles and feeding times can lead to obesity.
- These results illustrate the metabolic benefits of time-restricted feeding, which involves restricting food consumption to specific times of the day.
Factors associated with modern life, such as shift work and late-night eating, create a gap between the time meals are consumed and the light-dark cycle. This disruption is associated with overconsumption of food and an increased risk of obesity.
As such, there is growing interest in time-restricted eating (TRE). This is an eating pattern that matches the timing of food intake with the body’s circadian rhythm.
A new study using a mouse model published in chemistryWe investigated the mechanisms of weight gain associated with the timing of food intake and the light-dark cycle.
This study shows that the process of heat generation from calorie or heat generation in adipocytes also exhibits a rhythmic pattern consistent with the daily light-dark cycle.
Findings suggest that eating late at night disrupts this rhythm in fat cells, which can lead to lower energy expenditure and weight gain.
Dr. Satchidananda Panda, a professor at the Salk Institute, who was not involved in the study, said: medical news today:
“This exciting paper addresses one central issue in time-restricted eating (TRF). [or] Feeding (TRE) — Why TRF [and] TRE helps reduce fat mass. Many studies have shown that TRF reduces fat mass, but understanding the molecular mechanisms is critical to understanding which cells and biochemical pathways are activated under TRF to reduce fat. It helps identify and identify potential genes and proteins that may be targeted by drugs that mimic the benefits of TRF. “
For example, animals exhibit such variations in body temperature, hormone levels, food intake, sleep and activity levels.
an area of the brain called
The SCN receives light cues from the eye and synchronizes internal rhythms with the daily light-dark cycle.
In addition to the SCN, almost all cells in tissues and organs in the body have their own circadian clock. As a master clock, SCN coordinates peripheral clock activity.
Peripheral biological clocks periodically influence the expression of various genes, including those involved in metabolic processes such as glucose and fat metabolism.
In addition to light exposure, external cues such as time of food intake also affect circadian rhythms, but their effects are primarily exerted through peripheral biological clocks.
In other words, the SCN generates a rhythm of food intake and activity levels, ensuring that these activities coincide with the animal’s active period.
For example, mice are nocturnal animals and most food intake occurs during the dark or active period. The timing of their food intake influences the peripheral biological clock.
In animals, the time of food intake and the light-dark cycle are consistent.
Modern lifestyles, including shift work and exposure to blue light, are increasingly causing discrepancies in food intake and light-dark cycles.
The researchers used mice maintained on a high-fat diet as a model of obesity due to excessive caloric intake.
Moreover, mice fed a high-fat diet during the inactive (light) period gained even greater weight than mice maintained on the same diet during the active period, despite consuming the same amount of calories. indicates
Consistent with this, time-restricted feeding aims to optimize metabolic health by matching food intake to the circadian rhythms observed in metabolic processes.
However, the mechanisms underlying this association between eating food at the wrong time of day and metabolic health are not fully understood.
In the present study, we investigated the mechanisms underlying weight gain in mice fed a high-fat diet during the inactive period more than mice fed the same diet during the active period.
Most experiments were performed at 30 °C, where mice expend minimal energy to maintain a constant body temperature. The researchers found that mice fed during the inactive period expended less energy than mice fed during the active period.
In their paper, the researchers suggest that a potential reason for lower energy expenditure in mice fed during periods of inactivity may be that fewer calories are expended as heat after a meal. I cited other studies that suggest that there is
Researchers note that extra calories consumed during a meal may be stored as fat or dissipated as heat in a process known as diet-induced thermogenesis.
Brown adipose tissue, one of the major types of adipose tissue, is known to generate heat from some of the excess calories after food intake. On the other hand, the other major adipose tissue, white adipose tissue, is specialized in storing energy as fat.
However, under certain circumstances, white adipose tissue can also differentiate into beige adipocytes to generate heat from calories.
Therefore, the researchers investigated whether the lower energy expenditure of mice fed during periods of inactivity could be explained by differences in thermogenesis levels of adipocytes or adipocytes in adipose tissue. rice field.
To investigate the role of adipocyte-mediated thermogenesis, researchers used a genetically engineered mouse model and showed enhanced thermogenesis in adipocytes. Accelerating thermogenesis of adipocytes in mice prevented weight gain from being fed a high-fat diet during periods of inactivity.
Genetically engineered mice also showed higher levels of beige adipocytes in white adipose tissue.
Furthermore, adipocytes from genetically engineered mice cultured in the laboratory showed increased levels of metabolites associated with the futile creatine cycle. It is one of several different pathways that burn energy.
During the futile creatine cycle, ATP, the cellular energy currency, is utilized by creatine to produce creatine phosphate, which is converted to creatine. This dissipates the energy stored in ATP as heat.
The results of these experiments suggest that low levels of adipocyte thermogenesis may have contributed to the increased weight gain in mice fed during periods of inactivity. Furthermore, lower levels of wasted creatine cycling may explain these results.
To further examine the involvement of the creatine cycle, researchers used another genetically engineered mouse model that does not express one of the key enzymes involved in the futile creatine cycle in adipocytes.
A lack of enzymes involved in the adipocyte creatine cycle resulted in weight gain during both active and inactive periods.
This suggests that the futile creatine cycle in adipocytes contributes to the observed reduction in weight gain in active phase-fed mice.
In subsequent experiments, the researchers found that creatine levels and genes involved in creatine metabolism oscillated over a 24-hour period (i.e., rhythms were shown in fat cells).
Creatine levels peaked during the active phase in adipocytes from mice fed a high-fat diet during the active phase. In contrast, mice fed a high-fat diet during the inactive period showed decreased creatine circulation during the active period.
Given the rhythm of creatine circulation, researchers investigated the role of the peripheral adipocyte biological clock in regulating the creatine pathway.
Mice lacking a master clock protein called BMAL1 in adipocytes fed a high-fat diet during active or inactive periods gained weight comparable to control mice fed a high-fat diet during inactive periods. rice field.
Moreover, mice that did not express BMAL1 also showed reduced creatine circulation in adipocytes. In another experiment, researchers found that creatinine supplementation helped reduce the effects of lack of BMAL1 expression on weight gain.
These experiments suggest that the circadian clock in intact adipocytes may be essential for the enhanced thermogenesis and weight loss observed when feeding times are adjusted to match the light-dark cycle. increase.
Furthermore, this increase in thermogenesis was at least partially due to increased creatine circulation.
Previous
In this study, the researchers found that upregulating the BMAL1 gene in adipocytes reduced weight gain and improved metabolic health in mice fed a high-fat diet.
In addition, mice expressing higher levels of BMAL1 also exhibited greater creatine cycling and increased expression of genes involved in creatine metabolism. These results suggest that enhanced activity of the adipocyte circadian clock is sufficient to induce weight loss, possibly by increasing thermogenesis via the creatine cycle.
Overall, the current study suggests that a deviation from feeding time and creatine cycle-mediated thermogenic rhythm in adipocytes may lead to decreased energy expenditure and weight gain.
Despite the implications of the current study, more research is needed to determine whether time-restricted diets have the same impact on energy expenditure in humans.
“Since this study was performed in mice, it needs to be repeated in other animals and humans before the results can be generalized,” said Dr. Roberto Refinetti, a professor at the University of New Orleans.
In a commentary accompanying the paper, Dr. Lawrence Cazak, an assistant professor at McGill University, and Dr. Damien Lagarde, a postdoctoral fellow at McGill University, state:
“It is worth investigating whether creatine becomes limiting in situations of nutrient overload, where dietary creatine supplementation may enhance fat cell energy dissipation. Presumably, this link is bi-directional when regulating effectors of quantity and thermogenesis, with adipocyte-selective loss of components mediating the futile creatine cycle altering meal times when food is freely available. Understanding this relationship may help elucidate the relationship between adipose tissue metabolism and energy intake.”
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