Circadian rhythms, widely distributed in animals, are regulated by circadian clocks and integral to the normal functioning of numerous physiological processes. In mammals, the circadian clock generates approximately 24-h rhythms in feeding behavior. Specifically for the liver, the rhythmic expression of clock genes has recently been reported in rats and mice. Studies in mice have uncovered potential connections between circadian clocks and many aspects of metabolism, including energy generation, macromolecule metabolism, and detoxification. However, the expression of clock genes in the liver of pigs has not been exploited.

As the hydrolyzed product of chitosan, chitosan oligosaccharide (COS) is a mixture of oligomers. It has been found that COS reduced hepatic lipid accumulation in diabetic rats, but whether maternal COS supplementation has the similar effect in hepatic lipid metabolism in the offspring remains unclear.

In the paper in BIOLOGICAL RHYTHM RESEARCH, researchers from the Institute of Subtropical Agriculture, Chinese Academy of Sciences (ISA) used real-time PCR and Western Blot methods to clarify the expression of major circadian clock genes in the liver, and possible association with hepatic cholesterol accumulation in suckling piglets.

This team found that dietary supplementation with COS in sows significantly increasd the total cholesterol (total CHO), high-density lipoprotein- cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) levels in the liver and plasma in the suckling piglets on day 14. Notably, these results were contrast with previous studies that directly adding COS in diets could reduce hepatic lipid accumulation. However, these discoveries were not found in newborn piglets (on day 0).

Hepatic lipid metabolism and cholesterol synthesis have long been known to be subject to circadian regulation, and CLOCK/BMAL1 is important positive circadian clock elements. Above all, it has been reported that Bmal1 is a critical negative regulator of adipocyte development in the mice. However, there was no similar study in the liver of pigs. In their study, researchers found that the relative expression of CLOCK and BMAL1 were significantly inhibited, and expression of negative circadian clock element Per1, but not Per2, was upregulated. Thus they ventured a predication that maternal supplementation with COS upregulated the expression of Per1, which in turn, suppressed the clock genes CLOCK/BMAL1, which contributed to the hepatic cholesterol accumulation in suckling piglets. Of course, this speculation need more evidence to support.

In short, it is noteworthy that researchers could regulate the hepatic lipid metabolism in the suckling offspring via adjusting the maternal diets during lactation period, or circadian clock elements in the liver. Consequently, it also provides new reference to human nutrition.

This work was supported by the Major Project of Hunan Province [grant number 2015NK1002]; the National Key Technology Research and Development Program of the Ministry of Science and Technology of China under Grant (2012BAD39B00), and Key Technology Support Program of Jiangxi Province under Grant (No. 20151BBF60006).

The study entitled "Maternal chitosan oligosaccharide supplementation affecting expression of circadian clock genes, and possible association with hepatic cholesterol accumulation in suckling piglets" has been published in the December issue of Biological Rhythm Research, details could be found at http://www.tandfonline.com/doi/full/10.1080/09291016.2015.1108059

Contact: WU Xin, YIN Yulong

E-mail: wuxin@isa.ac.cn; yinyulong@isa.ac.cn

Institute of Subtropical Agriculture, Chinese Academy of Sciences