Obesity is an increasing health concern in modern society and in order for this to be successfully addressed there is a demand for a greater understanding of natural long term control of body weight and energy balance. The Siberian hamster provides a model of seasonal weight and energy regulation. Hamsters were studied under either long-day (LD) conditions (8 hours dark: 16 hours light) to promote weight gain, or short-day (SD) photoperiod (16 hours dark: 8 hours light) to induce weight loss. Weight loss in SD can be as much as 40% and identification of the factors involved in initiation and regulation of this weight loss may provide key understanding of long term weight control that could be applied to the treatment of obesity. Chronic central thyroid hormone administration resulted in body weight gain and reversed the catabolic effects of SD, while also reducing the incidence of energy saving torpor bouts, thereby promoting a LD, relatively fat phenotype. Further studies demonstrated that fibroblast growth factor 21 (FGF21) also plays a role in regulating body weight. Continuous peripheral administration of FGF21 triggered weight loss and increased utilisation of fat stores, promoting a SD relatively lean phenotype. Interestingly, these effects of FGF21 were found to be greatest in LD hamsters which initially had larger fat reserves and overall body weight and only slight effects were seen on lean SD hamsters. The overall aim of this thesis was to investigate potential mechanisms for the natural photoperiodic regulation of body weight and energy metabolism observed in the Siberian hamster in order to identify novel factors involved in long term weight control. These studies suggest that the initial energy status of the hamster is important for determining the response to weight altering interventions. They also suggest that central thyroid hormone may be a key factor initiating body weight gain in the transition from SD to LD, but that peripheral signals such as FGF21 are perhaps equally important for maintaining long term energy balance.