Shinobu Seki

Early nocturnal meal skipping alters the peripheral clock and increases lipogenesis in mice

BackgroundIn humans, skipping meals, especially breakfast, has been associated with obesity and other related syndromes. Recent studies in rodents suggest that fasting and feeding times are potential factors that affect the peripheral circadian clocks and metabolism. However, the link between fasting and obesity in rodents has yet to be fully demonstrated.MethodWe conducted early nocturnal fasting (ENF) from zeitgeber time (ZT) 12 to 18 for 4 consecutive days in C57B6 mice. The first set of experiments was performed under ad libitum conditions, where ENF and free-feeding (FF) control groups were compared. The second set was performed under isocaloric adjustment by restricting the diet to 90% of the basal intake of ENF mice. Calorie-restricted ENF (ENF-CR) mice were then compared with isocaloric controls (IC-control). Body weight, food intake, core body temperature, activity, adiposity, and clock-related gene expression levels in the liver and adipose tissues were investigated. A stable isotopic analysis was also conducted to estimate de novo lipogenesis fluxes.ResultsIn the ad libitum condition, the ENF mice ate more during the day, increased their overall daily food intake and gained more weight than FF-control mice. The amplitude of the body core temperature rhythm in ENF mice was also lower than in the FF-controls. Under isocaloric conditions, ENF-CR attenuated the CR-induced body weight loss, compared with the IC-control. ENF-CR also altered the acrophase time of the expression of the clock genes, which is associated with time-shift of genes involved in lipid metabolism and increased lipogenesis, compared with the IC-control.ConclusionsENF in nocturnal mice disturbs the peripheral clock and increases de novo lipid synthesis and results in a predisposition to obesity.

Voluntary wheel running is beneficial to the amino acid profile of lysine-deficient rats

Rats voluntarily run up to a dozen kilometers per night when their cages are equipped with a running wheel. Daily voluntary running is generally thought to enhance protein turnover. Thus, we sought to determine whether running worsens or improves protein degradation caused by a lysine-deficient diet and whether it changes the utilization of free amino acids released by proteolysis. Rats were fed a lysine-deficient diet and were given free access to a running wheel or remained sedentary (control) for 4 wk. Amino acid levels in plasma, muscle, and liver were measured together with plasma insulin levels and tissue weight. The lysine-deficient diet induced anorexia, skeletal muscle loss, and serine and threonine aminoacidemia, and it depleted plasma insulin and essential amino acids in skeletal muscle. Allowing rats to run voluntarily improved these symptoms; thus, voluntary wheel running made the rats less susceptible to dietary lysine deficiency. Amelioration of the declines in muscular leucine and plasma insulin observed in running rats could contribute to protein synthesis together with the enhanced availability of lysine and other essential amino acids in skeletal muscle. These results indicate that voluntary wheel running under lysine-deficient conditions does not enhance protein catabolism; on the contrary, it accelerates protein synthesis and contributes to the maintenance of muscle mass. The intense nocturnal voluntary running that characterizes rodents might be an adaptation of lysine-deficient grain eaters that allows them to maximize opportunities for food acquisition.