A single daily meal at the beginning of the active or inactive period inhibits food deprivation–induced fatty liver in mice

Abstract Food deprivation (FD) induces hepatic steatosis in both rodents and humans. Although body composition, age, and sex influence hepatic triglyceride (TG) levels after FD, whether feeding patterns affect FD-induced liver TG increases is unknown. We hypothesized that restricted feeding (RF) of 1 meal per day during the active or inactive period (especially the inactive period) augments FD-induced elevation of liver TGs because RF in the inactive period impairs the circadian rhythm. Triglyceride levels and the expression of genes related to TG metabolism in the liver were examined by a bioassay and real-time reverse transcription–polymerase chain reaction, respectively. In the first experiment, when compared to nonfasted mice, mice that fasted for 24 hours showed a 1.5-fold (FD starting during the inactive period) to 3-fold (FD started during the active period) increase in liver TG levels. This experiment showed that TG levels depend upon the starting time of FD. In the second experiment, mice were given free access to food for 3 hours at the beginning of either the inactive ("supper-only") or the active ("breakfast-only") period for 2 weeks. Restricted feeding inhibited the FD-induced increases in liver and serum TG levels, serum free fatty acids, and the expression of genes related to fatty acid uptake in the liver, including fatty acid transport protein 1 ( Fatp1 ) and 4 ( Fatp4 ). Unexpectedly, compared to free feeding, RF during the active or inactive period resulted in resistance to FD-induced fatty liver. This is the first study to demonstrate that feeding patterns affect FD-induced TG accumulation in the mouse liver.