1 The blood glucose-lowering ecacy of rosiglitazone (RSG) and the mechanisms of associated weight gain were determined in dietary obese rats (DIOs). DIO and chow-fed rats received RSG 0.3 ± 30 mg kg 71 daily for 21 days. 2 In DIOs, plasma glucose and insulin concentrations were reduced by RSG at dosages of 3 and 10 mg kg 71, respectively. Homeostasis model assessment (HOMA) indicated the threshold for a reduction of insulin resistance was 1 mg kg 71 . Neither glucose nor insulin levels were aected by treatment in chow-fed rats. 3 RSG 0.3 mg kg 71 lowered free fatty acids (FFAs) in DIOs, whereas for plasma triglycerides (TGs), the threshold was 3 mg kg 71 . By contrast, the threshold for reducing packed red cell volume (PCV) and increasing cardiac mass was 10 mg kg 71 . Thus, the therapeutic index for RSG in DIOs was 43 and 410. 4 Energy intake and weight gain increased in treated DIOs (by 20% and 50 g, at 30 mg kg 71) and chow-fed rats (by 25% and 35 g, at 30 mg kg 71 ). In DIOs, these increases coincided with falls in plasma leptin (40% lower at 30 mg kg 71 ) and insulin (43% lower at 30 mg kg 71 ). By contrast, in chow-fed rats, weight gain and hyperphagia occurred without changes in either leptin or insulin. However, reductions in FFAs below 0.4 ± 0.3 mM were associated with hyperphagia and weight gain in DIO and chow-fed rats. 5 We conclude that increased energy intake and body weight did not attenuate the improved metabolism evoked by RSG in DIO rats, and that insulin action was enhanced at a dose 43 fold below the threshold for causing haemodilution and cardiac hypertrophy in DIO rats.

These data suggest that aspects of olanzapine-induced weight gain and metabolic abnormalities can possibly be modelled in female rats. It is suggested that olanzapine-induced hyperphagia acts as an initial stimulus which leads to weight gain, enhanced visceral adiposity and subsequent insulin resistance, although the latter may be ameliorated by compensatory responses in adiponectin levels. Prolactin elevation appears likely not to be involved in the weight gain, adiposity and metabolic changes seen in this model.

Many of olanzapine's (OLZ) actions in humans related to weight regulation can be modelled in female rats (Cooper et al., 2005). Such effects include weight gain, hyperphagia, enhanced visceral adiposity and elevated Levels of insulin and adiponectin. As sex differences have been reported in the effects of antipsychotic drugs, including OLZ, in rats, the current study extended our study in female rats by directly comparing the actions of OLZ in maLes using identical methodology. Individually housed male Han Wistar rats were administered OLZ twice daily (i.p.), at 0, 1, 2, and 4 mg/kg over 21 days. Both differences from, and simiLarities to, the data obtained in females were obtained. Males treated with OLZ showed reduced weight gain, enhanced visceral adiposity and reduced lean muscle mass. There were no accompanying changes in food or water intake. OLZ did not induce changes in plasma levels of insulin, leptin or glucose. Significant elevation of adiponectin was observed. OLZ-treated males displayed elevated prolactin and suppressed testosterone. OLZ's effects in humans can very clearly be most validly modelled in female rats, although the cause(s) of the sex difference in OLZ's actions in rats are not clear. However, the finding that significantly enhanced adiposity is seen in both male and female rats, in other animal species (mice and dogs) and in humans suggests that studies in male rats of OLZ's effects may be of value, by highlighting the consistent ability of OLZ to increase visceral adiposity. It is hypothesized that such adiposity is a key, clinically relevant, common component of OLZ's actions which may be, at Least partially, independent of both OLZinduced weight gain and hyperphagia, and which is induced reliably in male and female rats and other animal species. Possible mechanisms involved in the effects reported are discussed.

Canine obesity is a prevalent disease, but many owners are unaware of it, partly due to misperception of their dog's body shape. Body condition scoring (BCS) is a simple method of assessing body composition, but whether it can reduce owner misperception is unclear. Our aim was to determine the effect of a BCS system on owners' ability to estimate the body condition of their dog. Information from 110 dog owners attending three UK veterinary practices was gathered, by interview, between March and April 2013. First, owners were asked to determine their dog's body condition without guidance, and then reassess it using a five-point BCS chart. Most owners (85/110, 77 %) believed the chart to have improved their ability to estimate the condition of their dog correctly. However, only a weak agreement existed between owner estimates and those of the primary investigator, both with (kappa (κ) = 0·28; P < 0·001) and without (κ = 0·32; P < 0·001) the BCS chart. Furthermore, most owners incorrectly estimated their dog's body condition, both with (71/110; 64 %) and without (72/110; 65 %) the chart (P = 1·00), with underestimation being most common (with = 63/71, 89 %; without = 66/72, 92 %; P = 0·57). Owners of overweight dogs more commonly misperceived their dog's body condition, both with (BCS 1–3: 5/35, 14 %; BCS 4–5: 64/75, 85 %; P < 0·001) and without (BCS 1–3: 10/35, 28 %; BCS 4–5: 61/75, 81 %; P < 0·001) the BCS chart. Thus, use of a five-point BCS chart does not improve accuracy of owners' perception of their dog's body shape, despite the accompanying perception that it does.

Chronic cold exposure stimulates sympathetically driven thermogenesis in brown adipose tissue (BAT), resulting in fat mobilization, weight loss, and compensatory hyperphagia. Hypothalamic neuropeptide Y (NPY) neurons are implicated in stimulating food intake in starvation, but may also suppress sympathetic outflow to BAT. This study investigated whether the NPY neurons drive hyperphagia in rats that have lost weight through cold exposure. Rats exposed to 4°C for 21 days weighed 14% less than controls maintained at 22°C ( P < 0.001). Food intake increased after 3 days and remained 10% higher thereafter ( P < 0.001). Increased BAT activity was confirmed by 64, 96, and 335% increases in uncoupling protein-1 mRNA at 2, 8, and 21 days. Plasma leptin decreased during prolonged cold exposure. Cold-exposed rats showed no significant changes in NPY concentrations in any hypothalamic regions or in hypothalamic NPY mRNA at any time. We conclude that the NPY neurons are not activated during cold exposure. This is in contrast with starvation-induced hyperphagia, but is biologically appropriate since enhanced NPY release would inhibit thermogenesis causing potentially lethal hypothermia. Other neuronal pathways must therefore mediate hyperphagia in chronic cold exposure.