Recent pre-clinical and epidemiological evidence (1,2) suggests that temporal feeding patterns influence metabolic outcome, but the underlying mechanism has been obscured by our inability to control feeding patterns in laboratory animals. To overcome this, we have used a CLAMS-based system to investigate the effect of 3 weeks of grazing (consumption of 0.5g (mice) or 1/24th of the total food intake of ad libitum (AL)-fed controls (rats) every 30 mins during the dark phase (18.00-06.00h)) and meal feeding (MF: three 1hr periods of AL food access at 18.00h, 23.30h and 05.00h). Data cited are mean±SEM, with statistical comparisons performed by 1-way ANOVA and Bonferroni post hoc test.In 6 week-old male Sprague-Dawley (SD) rats grazing (n=7) and MF (n=6) reduced cumulative food intake (cFI) by 15% (P<0.0001 vs AL-fed controls (n=13)), but only MF reduced body weight gain (Day 18 ΔBW: 153.4±4.5g vs 173.2±3.5g (AL); P<0.05). Grazing elevated proportionate inguinal fat mass by 35% (P<0.01), without influencing epididymal or retroperitoneal fat, with abdominal fat storage efficiency being increased by 26% (P<0.01). MF did not alter adiposity. Tibial length and epiphyseal plate width (EPW) were unaffected by grazing or MF, but grazing shortened the hypertrophic zone by 16% (P<0.01).In 6 month-old male C57BL6 mice grazing increased cFI by 17% (P<0.01), and elicited a transient increase in ΔBW (0.25±0.62g (n=5) vs -1.06±0.19g (AL; n=6) at day 7; P<0.05). MF reduced cFI by 14% (P<0.05), with a sustained reduction in ΔBW (-2.73±1.12g (n=7) vs -1.01±0.29g at day 14; P<0.05). These effects were abolished in male ghrelin-null littermates (n=5-7).Given this ghrelin-dependency, we used automated blood sampling to characterise ghrelin profiles in 6 week-old male SD rats catheterised under isoflurane anaesthesia. AL-fed rats (n=9) showed the established (3) mid-light phase peak and late-dark phase nadir in circulating ghrelin (total). Grazing (n=4) and MF (n=4) elicited a marked anticipatory rise in ghrelin in the late-light phase (P<0.01 vs AL-fed rats), followed by a rapid decline as feeding commenced. However, MF also produced pre-prandial peaks before the mid- and end-dark phase meals (P<0.05), while grazing doubled circulating ghrelin in the last third of the dark phase (P<0.05).Our data demonstrate that feeding patterns influence fat mass, and that the effects of grazing and MF on weight gain are ghrelin-dependent. Intermittent ghrelin exposure, as produced by MF, is known to promote growth hormone (GH) secretion without elevating fat mass, whereas the temporal alignment of raised ghrelin and feeding activity produced by grazing, suppresses GH secretion and increases fat deposition (4,5). Thus, our data imply that grazing behaviour may contribute to the current obesity crisis.