The metabolic program provoked by naringenin, appears to be a fed-to-fasted transition in the lipid metabolism of primary hepatocytes.
Early studies suggested that glycogen is converted into fat in the adipose tissue and the dynamic regulation of adipose glycogen may serve as an energy sensor in coordinating glucose and lipid metabolism during the fasted to fed transition (Markan et al., 2010).
Obesity is associated with a variety of abnormalities in metabolic homeostasis, including insulin resistance, glucose intolerance, hyperlipidemia, and a condition described as "metabolic inflexibility", referring to impairment in normal switching from fatty acid to glucose utilization in the fasted to fed transition (Storlien et al, 2004; Harmancey et al, 2008).
The requirement of a RXR binding partner leads to competitive inhibition at the level of receptor activation, offering a transcriptional layer of control over fasted-to-fed transition [42], [43], [44].
Primary BAT cells were 'fasted' and then given glucose, to mimic the fasted-to-fed transition.
Glucokinase expression in the fasted to re-fed transition was markedly induced in Pten+/− mouse livers, 6 indicating increased insulin sensitivity, suggesting basal HGP regulation is under the control of factors besides insulin signaling, such as neural control.
One possible immediate mechanism is that an increase in glucose availability may directly signal the transition from the fasted to fed state and thus enable nonessential physical activity energy expenditure above basal levels (40).
To establish a model of hepatic TG accumulation, we treated cells with a physiological mixture of fatty acids, in a similar ratio to that most commonly observed in the systemic circulation of humans (24), in the absence or presence of insulin, thus mimicking, to some extent, the transition from a fasted to a fed state.
Mice in fasted group were fasted overnight and sacrificed.
First, the time scale of the model is days, weeks and months and therefore does not address within-day dynamics such as the transition from fed to fasted states.
Although it could be contended that the higher afternoon/evening glucose variability in the fasting group might simply reflect an initial transition from a lower starting (ie, still fasted) value, this effect would be apparent in the first week as well as in the last.
