- Eating at odd times of the day is associated with increased food intake and an increased risk of obesity.
- A new study in mice suggests that weight gain due to food consumption at inappropriate times may be attributed to impaired thermogenesis, the process of burning calories to release heat, by fat cells or fat cells..
- Adipocytes showed rhythmic changes in thermogenesis levels in line with light and dark cycles, and misalignment of adipocyte cycles with feeding times may lead to obesity.
- These findings explain the metabolic benefits of time-restricted feeding, including restricting food consumption to certain hours of the day.
Factors associated with modern life, such as shift work and late-night eating, have disrupted the alignment between mealtime and the cycles of light and dark. This disorder is associated with overeating and an increased risk of obesity.
As such, there was an increase in interest in time-restricted eating (TRE), an eating pattern that balances eating time with the body’s circadian rhythms.
A new study using a mouse model published in SciencesShe studied the mechanisms of weight gain associated with the timing of food consumption and the cycles of light and dark.
The study indicates that the process of caloric thermogenesis, or thermogenesis, in adipocytes also exhibits a circadian pattern consistent with the daily light-dark cycle.
The results suggest that eating late at night may disrupt this rhythm in adipocytes, resulting in lower energy intake and weight gain.
Satchidananda Panda, PhD, a professor at the Salk Institute, who was not involved in the study, said, Medical news today:
This exciting paper addresses one central question in time-restricted eating (TRF) [or] Nutrition (TRE) – Why TRF [and] TRE helps reduce fat mass. Although several studies have shown that TRF reduces fat mass, understanding the molecular mechanism helps identify the cells and biochemical pathways that are activated under TRF to reduce fat and identify potential genes or proteins that can be targeted by drugs to mimic the benefits of TRF.”
For example, animals show such fluctuations in body temperature, hormone levels, food intake, sleep and activity levels.
The area of the brain is called
The SCN receives light signals from the eye and synchronizes its internal rhythms with the daily cycles of light and dark.
In addition to the SCN, almost all cells in tissues and organs in the body have their own biological clock. As a master clock, the SCN coordinates the activity of peripheral clocks.
Peripheral biological clocks influence the expression of a variety of genes in a cyclical manner, including those involved in metabolic processes, such as glucose and lipid metabolism.
Besides exposure to light, external cues such as when to eat also influence circadian rhythms but exert their influence mostly through peripheral circadian clocks.
In other words, the SCN generates rhythms in food intake and activity levels so that these activities coincide with the animal’s active period.
For example, mice are nocturnal animals, and most of their food intake occurs during the dark or active period. The timing of their food intake affects the peripheral biological clocks.
In animals, the time of eating and the cycles of light and dark are aligned.
Modern lifestyles, including shift work and exposure to blue light, have increasingly led to an imbalance between food intake and the light-dark cycle.
The researchers used mice on a high-fat diet as a model for obesity due to excessive calorie intake.
In addition, rats fed a high-fat diet during the inactivity (light) period show greater weight gain than those fed the same diet during the activity period, despite consuming the same amounts of calories.
Consistent with this, time-restricted feeding aims to align food intake with circadian rhythms observed in metabolic processes to improve metabolic health.
However, the mechanisms behind this association between eating at the wrong time of day and metabolic health are not fully understood.
In the current study, the researchers examined the mechanisms underlying weight gain further in mice fed a high-fat diet during the inactivity period compared to those fed the same diet during the active period.
Most of the experiments were conducted at 30 °C when the mice expend a minimum amount of energy to maintain a constant body temperature. The researchers found that mice fed during the inactivity period showed lower energy consumption than mice fed during the active period.
In their paper, the researchers cite other research that suggested that a possible reason for the lower energy expenditure in mice fed during an inactivity period could be the dissipation of fewer calories as post-meal heat.
The researchers note that excess calories consumed during a meal can be stored as fat or dissipated as heat in a process known as diet thermogenesis.
Brown adipose tissue, one of the main types of adipose tissue, is known to produce heat from some extra calories after eating. On the other hand, white adipose tissue, which is the other main type of adipose tissue, is specialized in storing energy in the form of fat.
However, under certain conditions, white adipose tissue can differentiate into beige adipocytes, which can also generate caloric heat.
Hence, the researchers examined whether the lower energy expenditure in mice fed during the period of inactivity could be explained by differences in thermogenesis levels in fat cells or fat cells in adipose tissue.
To study the role of adipocyte-mediated thermogenesis, the researchers used a genetically modified mouse model that demonstrated enhanced thermogenesis in adipocytes. Enhanced thermogenesis in mice adipocytes prevented weight gain because they were fed a high-fat diet during the inactive period.
The transgenic mice also showed higher levels of beige fat cells in the white adipose tissue.
In addition, adipocytes from transgenic mice raised in vitro showed increased levels of metabolites associated with the futile creatine cycle. The useless creatine cycle is one of the many different pathways through which cells burn off excess energy in the form of heat.
During a useless creatine cycle, creatine uses ATP, the cell’s energy currency, to produce phosphocreatine, which is then converted to creatine. This results in the energy stored in ATP being dissipated as heat.
The results of these experiments suggest that lower levels of thermogenesis in adipocytes may have contributed to the increased weight gain in mice fed during the period of inactivity. Furthermore, low levels of a useless creatine cycle may explain these findings.
To further study the involvement of the creatine cycle, the researchers used a different transgenic mouse model that did not express one of the key enzymes involved in the futile creatine cycle in adipocytes.
Deficiency of the enzyme involved in the creatine cycle in adipocytes resulted in weight gain during the active and inactive periods.
This indicates that the useless creatine cycle in adipocytes contributes to the reduced weight gain observed in mice fed during the active period.
In subsequent experiments, the researchers found that levels of creatine and the genes involved in creatine metabolism fluctuated over a 24-hour period (that is, showed a rhythm in adipocytes).
Creatine levels peaked during the active period in the adipocytes of mice fed a high-fat diet during the active period. In contrast, rats fed a high-fat diet during the inactive phase showed a decrease in the creatine cycle during the active phase.
Given the rhythm of the creatine cycle, the researchers examined the circadian role of peripheral adipocytes in regulating the creatine pathway.
Mice lacking a key clock protein called BMAL1 in adipocytes fed a high-fat diet during the active or inactive period showed similar levels of weight gain as control mice fed a high-fat diet during the inactive phase.
Moreover, mice that did not express BMAL1 also showed a decrease in the creatine cycle in adipocytes. In a separate trial, researchers found that creatinine supplementation helped mitigate the effects of the absence of BMAL1 expression on weight gain.
These experiments suggest that a healthy adipocyte biological clock may be essential for the enhanced thermogenesis and weight loss observed when feeding times are aligned with the light-dark cycle.
Furthermore, this increase in thermogenesis was at least partly due to the increase in the creatine cycle.
In the current study, researchers found that enhancing the expression of the BMAL1 gene in adipocytes reduced weight gain in mice fed a high-fat diet and improved metabolic health.
Moreover, mice expressing higher levels of BMAL1 also showed increased creatine turnover and increased expression of genes involved in creatine metabolism. These results suggested that the circadian-enhanced activity of adipocytes was sufficient to induce weight loss, most likely by increasing thermogenesis mediated by the creatine cycle.
Overall, the present study indicates that the imbalance of feeding time with the thermogenesis rhythm mediated by the creatine cycle in adipocytes can lead to decreased energy intake and weight gain.
Despite the implications of the current study, more research is needed to determine whether time-restricted eating produces the same effects on energy expenditure in humans.
Roberto Refiniti, PhD, a professor at the University of New Orleans, noted that “the study was done in mice, so it needs to be repeated in other animals and in humans before the results are generalized.”
In a comment accompanying the paper, Lawrence Kazak, PhD, assistant professor at McGill University, and Damien Lagarde, PhD, also a postdoctoral fellow at McGill University noted:
“It would be useful to explore whether creatine becomes restricted in a case of nutritional overload as dietary creatine supplementation can enhance adipocyte energy dissipation. If TRF regulates creatine abundance and thermogenetic effectors of the useless creatine cycle, this link is probably bidirectional, so that Adipocytes selective loss of components that mediate the useless creatine cycle alters when food is eaten when food is freely available. Understanding this relationship can help clarify the link between adipose tissue metabolism and energy intake.”
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