Metabolic disorders induced by high-fat feeding in rodents evoke some, if not all, of the features of human metabolic syndrome. The occurrence and severity of metabolic disorders, however, varies according to rodent species, and even strain, as well as the diet. Therefore, in the present study, we investigated the long-term obesogenic and diabetogenic effects of three high-fat diets differing by their fat/carbohydrate ratios. Sprague-Dawley rats were fed a control high-carbohydrate and low-fat diet [HCD; 3:16:6 ratio of fat/carbohydrate/protein; 15.48 kJ/g (3.7 kcal/g)], a high-fat and medium-carbohydrate diet [HFD1; 53:30:17 ratio of fat/carbohydrate/protein; 19.66 kJ/g (4.7 kcal/g)], a very-high-fat and low-carbohydrate diet [HFD2; 67:9:24 ratio of fat/carbohydrate/protein; 21.76 kJ/g (5.2 kcal/g)] or a very-high-fat and carbohydrate-free diet [HFD3; 75:0:25 ratio of fat/carbohydrate/protein; 24.69 kJ/g (5.9 kcal/g)] for 10 weeks. Compared with the control diet (HCD), rats fed with high-fat combined with more (HFD1) or less (HFD2) carbohydrate exhibited higher BMI (body mass index; +13 and +10% respectively; P<0.05) and abdominal fat (+70% in both HFD1 and HFD2; P<0.05), higher plasma leptin (+130 and +135% respectively; P<0.05), lower plasma adiponectin levels (-23 and -30% respectively; P<0.05) and impaired glucose tolerance. Only the HFD1 group had insulin resistance. By contrast, a very-high-fat diet devoid of carbohydrate (HFD3) led to impaired glucose tolerance, insulin resistance and hypoadiponectinaemia (-50%; P<0.05), whereas BMI, adiposity and plasma leptin did not differ from respective values in animals fed the control diet. We conclude that increasing the fat-to-carbohydrate ratio to the uppermost (i.e. carbohydrate-free) in a high-fat diet prevents the development of obesity, but not the prediabetic state (i.e. altered glucose tolerance and insulin sensitivity).

The Syrian hamster is a rodent species in which the photoperiodic change in the melatonin peak duration is pivotal for the synchronization of annual functions, like reproduction. In this species, the activity of arylalkylamine N-acetyltransferase (AANAT), the key enzyme for the rhythmic synthesis of melatonin, is precisely controlled and time-gated, suggesting regulatory mechanisms different from those in the rat or mouse. At the beginning of the night, norepinephrine (NE) elicits a rapid and sustained phosphorylation of CREB into pCREB and a transient synthesis of the immediate early gene products c-FOS and c-JUN that peak 3 h after dark onset. c-FOS synthesis requires both pCREB and the pERK1/2 pathways. Interestingly, injection of the protein synthesis inhibitor cycloheximide before, but not after, the c-FOS/c-JUN peak markedly reduces Aanat mRNA levels. This finding suggests that the c-FOS/c-JUN dimer is required for transcriptional activation of the Aanat gene. During daylight, exogenous noradrenergic stimulation cannot stimulate Aanat expression and, therefore, melatonin synthesis. The inhibitory transcription factor ICER is present in the pineal gland but with highest values when AANAT may be activated, suggesting the blockade takes place upstream of Aanat expression. Preliminary experiments indicate that the diurnal inhibition of AANAT occurs at the level of the adrenergic receptor signalling pathway, but it is not known whether this is sufficient to explain the pineal resistance to NE during the daytime. Together, these findings demonstrate that AANAT regulation in the Syrian hamster requires a complex intracellular signalling cascade, different from that described in laboratory rodents like mice and rats.

Species differences have been reported for the nighttime regulation of arylalkylamine N-acetyltransferase (AA-NAT), the melatonin rhythm-generating enzyme. In particular, de novo synthesis of stimulatory transcription factors is required for Aa-nat transcription in the Syrian hamster but not in the rat pineal gland. The present work investigated the contribution of phosphorylated cAMP-responsive element-binding protein, c-FOS, c-JUN, and JUN-B in the regulation of Aa-nat transcription in Syrian hamsters compared with rats. The nighttime pattern of cAMP-responsive element-binding protein phosphorylation and regulation by norepinephrine observed in the Syrian hamster was similar to those reported in the rat. On the contrary, strong divergences in c-FOS, c-JUN, and JUN-B expression were observed between both species. In Syrian hamster, predominant expression of c-FOS and c-JUN was observed at the beginning of night, whereas a predominant expression of c-JUN and JUN-B was observed in the late night in rat. The early peak of c-FOS and c-JUN, known to form a stimulatory transcription dimer, suggests that they are involved in the nighttime stimulation of Aa-nat transcription. Indeed, early-night administration of a protein synthesis inhibitor (cycloheximide) markedly decreased AA-NAT mRNA levels in Syrian hamster. In the rat, high levels of JUN-B and c-JUN, constituting an inhibitory transcription dimer, are probably involved in the late-night inhibition of Aa-nat transcription. Early-night administration of cycloheximide actually increased AA-NAT mRNA levels toward the late night. Therefore, composition and timing of the pineal activator protein-1 complexes differ between rat and Syrian hamster and may be an activator (Syrian hamster) or an inhibitor (rat) of Aa-nat transcription.