High-fat feeding in rodents leads to metabolic abnormalities mimicking the human metabolic syndrome, including obesity and insulin resistance. These metabolic diseases are associated with altered temporal organization of many physiological functions. The master circadian clock located in the suprachiasmatic nuclei controls most physiological functions and metabolic processes. Furthermore, under certain conditions of feeding (hypocaloric diet), metabolic cues are capable of altering the suprachiasmatic clock's responses to light. To determine whether high-fat feeding (hypercaloric diet) can also affect resetting properties of the suprachiasmatic clock, we investigated photic synchronization in mice fed a high-fat or chow (low-fat) diet for 3 months, using wheel-running activity and body temperature rhythms as daily phase markers (i.e. suprachiasmatic clock's hands). Compared with the control diet, mice fed with the high-fat diet exhibited increased body mass index, hyperleptinaemia, higher blood glucose, and increased insulinaemia. Concomitantly, high-fat feeding led to impaired adjustment to local time by photic resetting. At the behavioural and physiological levels, these alterations include slower rate of re-entrainment of behavioural and body temperature rhythms after 'jet-lag' test (6 h advanced light-dark cycle) and reduced phase-advancing responses to light. At a molecular level, light-induced phase shifts have been correlated, within suprachiasmatic cells, with a high induction of c-FOS, the protein product of immediate early gene c-fos, and phosphorylation of the extracellular signal-regulated kinases I/II (P-ERK). In mice fed a high-fat diet, photic induction of both c-FOS and P-ERK in the suprachiasmatic nuclei was markedly reduced. Taken together, the present data demonstrate that high-fat feeding modifies circadian synchronization to light.
