The mammalian clock regulates major aspects of energy metabolism, including glucose and lipid homoeostasis as well as mitochondrial oxidative metabolism. This study is to identify specific patterns of circadian rhythms for lipid homoeostasis in both female and male mouse livers, and to clarify gender disparity in coupling the peripheral circadian clock to lipid metabolic outputs by nuclear receptors. To achieve this, profiling the diurnal hepatic expression of genes encoding circadian clocks, nuclear receptors and lipid metabolic enzymes was performed. Hepatic lipid levels including cholesterol, triglyceride and non-esterified fatty acids (NEFAs) were monitored over a 24-h period. The cosinor analysis revealed that several genes encoding nuclear receptors and enzymes involved in the lipid metabolic pathway were rhythmically expressed in liver in phase with the peripheral clocks, which were correlated with the diurnal changes of hepatic lipid levels. Gender disparity was observed for circadian characteristics including mesor and amplitude values, accompanied with advances in acrophases in female mouse livers. Accordingly, gender differences were also observed in diurnal lipid homoeostasis. The identification of cycling patterns for lipid metabolic pathways in both female and male mouse livers may shed light on the development of gender-based treatment for human diseases related to the coordination of the cellular clock and control of lipid homoeostasis.Key words: Circadian rhythm, gender, lipid homoeostasis, liver, nuclear receptor.Abbreviations: Bmal1, brain and muscle Arnt-like protein 1; Clock, circadian locomotor output cycles kaput; Cry, cryptochrome; LXR, liver X receptor; Mesor, midline estimating statistic of rhythm; NEFA, nonesterified fatty acids; Per, period; PGC1, PPARg coactivator 1; PPAR, peroxisome proliferator-activated receptor; ROR, retinoid-related orphan receptor; RORE, ROR response element.Circadian rhythms are daily cycles of multiple molecular, biochemical, physiological and behavioural processes that are driven by an endogenous clock with an approximate 24-h periodicity. Circadian rhythms in mammals are governed substantially by the main time-keeping system, called the central circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian clocks also exist in most peripheral tissues and even in cultured cells. It is believed that the master circadian clock synchronizes the peripheral clocks through both neural and humoral factors, allowing animals to adapt their feeding, activity and metabolism to predictable rhythmic cycles. Environmental light is the predominant Zeitgeber (time-giver) to reset the intrinsic clocks. In addition, other cyclic inputs such as temperature, food, noise or social cues may also influence the phase of clocks (1-3).The central and peripheral clocks share common molecular circuitry. The circadian clockwork consists of two auto-regulatory feedback loops connected by a central pair of basic-helix-loop-helix (bHLH)-PAS (PER-ARNT-SIM)-cont...