Background:
Shift work is associated with an increased risk of obesity and metabolic syndrome [1]. Metabolic processes exhibit a circadian rhythm entrained by the light-dark cycle and food intake [2]. We aimed to investigate the effect of restricted feeding (RF) on circadian variation in liver metabolism (enzyme mRNA) and thus establish the potential benefits of RF in health and obesity.
Methods:
Male C57BL/6 mice (8wks old) housed in a 12h light-dark cycle were split into 2-groups (n=120/group) and fed with either a standard laboratory diet (SLD; 14%kJ from fat) or a high fat diet (HFD; 60%kJ from fat) for 12wks. After 4wk diet acclimatisation the mice were split into 3-groups/diet (n=40/group) and fed either ad libitum (AL) or only during the light phase (LP) or dark phase (DP) for the remaining 8wks. Mice were sacrificed at 3h intervals across a 24h period (n=5 mice/time-point/group) starting at 0600h. Weight gain, plasma glucose, C-peptide & triglycerides concentrations were measured along with liver mRNA levels for mRNA from liver glucose transporter 2 (Slc2a2), insulin receptor (Irβ), glycogen synthase (Gys2), acetyl-CoA carboxylase (Accα) and carnitine palmitoyltransferase (Cpt1α).
Results:
HFD-AL mice gained more weight (P<0.001) and gonadal fat (P<0.001) than all other groups including the HFD-LP&DP mice. Plasma triglyceride levels were reduced in HFD-LP&DP mice compared to HFD-AL mice (P<0.001). Plasma C-peptide levels were higher in SLD-DP&LP mice compared to SLD-AL mice (P<0.01) and in HFD-DP mice compared to HFD-AL mice (P<0.01). Liver mRNA levels of Slc2a2, Irβ, Gys2, Accα and Cpt1α exhibited a circadian rhythm in SLD-AL mice with desynchrony occurring in HFD-AL conditions (P<0.05). RF (DP&LP) in HFD mice, re-established circadian rhythmicity (P<0.05) and LP-feeding reversed the circadian profile (P<0.01) in line with food intake.
Conclusion:
Restricted feeding prevents the disruption of circadian metabolic markers and is associated with reduced weight gain.