A research panel at the Texas A&M Health Science Center have investigated how body clock dysregulation affect obesity-related metabolic disorders. They have found that body clock dysregulation could lead to obesity.
According to Dr. Chaodong Wu, associate professor in the department of nutrition and food sciences of Texas A&M's College of Agriculture and Life Sciences, animal sleeping and eating patterns, including those of humans, are subject to a circadian rhythmicity. Circadian clocks in peripheral tissues and cells drive daily rhythms and coordinate many physiological processes, including inflammation and metabolism.
The researchers noted that the disruption of circadian clock regulation plays a key role in the development of metabolic diseases, including obesity and diabetes. The study affirms that eating unhealthy foods at the wrong time may lead to negative consequences. The researchers suggest that time-based treatment may provide better management of metabolic diseases.
Earlier, the studies have shown an association between the dysregulation of circadian or body clock rhythms and some metabolic disorders. In those studies, core clock genes were removed from the mice. They found alteration in metabolism and rise in obesity but the mechanism remained unknown.
This study shows that the key components of inflammation in obesity, macrophages (immune cells) contain cell-autonomous circadian clocks that have been shown to gate inflammatory responses.
To test the hypothesis, the panel of researchers conducted experiments with "reporter mice" in which the circadian rhythmicity of various types of cells could be monitored by looking at their reporter activity. A group of mice were put on a 12-hour light-dark cycle and were fed a high-fat diet and another group of reporter mice were fed a low-fat diet. The team observed the effects of a high-fat diet on circadian clock rhythmicity and inflammatory responses in immune cells, or macrophages.
The team also conducted "bone marrow transplantation" experiments to define a unique role for circadian clock dysregulation in metabolic disorders. The rhythmicity of circadian clocks was found to be disrupted only in a specific type of immune cells. A number of physiological and immunological assays also were performed on the mice.
When mice were fed a high-fat diet, the rhythmicity of circadian clocks in immune cells of fat tissue is dysregulated by a prolonged rhythmic period. It increased the accumulation of immune cells in fat tissue and decreased whole-body insulin sensitivity.
The study findings were published in the Journal of Biological Chemistry website.
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