ORIGINAL ARTICLE: The approach to the mechanism of calcitonin gene‐related peptide‐inducing inhibition of food intake

The aim of this study was to investigate the anorectic mechanism of calcitonin gene‐related peptide (CGRP) in rats. Intraperitoneal injection of CGRP (50 μg/kg) resulted in decline (p < 0.05) in the food intake of rats at 0.5, 1, 2 and 4 h in comparison with saline control. Compared with saline‐treated group, the levels of hypothalamic 3′,5′‐cyclic adenosine monophosphate (cAMP) and plasma glucagon were increased (p < 0.05) in CGRP‐treated group, but insulin level was decreased (p < 0.05). No significant changes (p > 0.05) in the plasma leptin were observed between two treatment groups. Calcitonin gene‐related peptide injection down regulated (p < 0.05) both neuropeptide Y (NPY) and melanin‐concentrating hormone (MCH) genes at mRNA levels, but up regulated (p < 0.05) the expression of cholecystokinin (CCK) gene. The correlations analysis showed that food intake was negatively correlated (p < 0.05) with CCK mRNA, cAMP and glucagon levels. Moreover, there existed negative correlations (p < 0.05) between MCH mRNA and glucagon levels, and positive correlations (p < 0.05) between insulin and leptin levels. The results showed that cAMP acting as the second messenger may play a vital role in the anorectic effects of CGRP. Calcitonin gene‐related peptide could stimulate anorexigenic neuropeptides (i.e. CCK) and/or inhibit orexigenic neuropeptides (i.e. NPY and MCH) expression, and ultimately suppressed food intake that was functionally coupled to cAMP/PKA pathway activation.     

Effects of chronic mild food restriction on behavior and the hypothalamic malonyl‐CoA signaling pathway

Depression induces anorexia, leading to suppressed feeding behaviors and energy intake. Previously, we revealed that chronic social defeat induced a mild suppression of feeding in rats with elevated levels of hypothalamic malonyl‐CoA which regulates feeding. Therefore, we attempted to elucidate the effects of chronic mild food restriction on behavior and on hypothalamic malonyl‐CoA. The chronic mild food restricted rats were fed a restricted diet approximately 80% to 90% amount of diet compared to the control for 5 weeks. Ratios of restriction were adjusted with feed consumption in the chronic social defeat stressed rats. Chronic mild food restricted rats exhibited a suppression of body weight gain similar to that of the chronic social defeat stressed rats. Also these rats showed increased time spent in the center area of an open field (OF), prolonged immobility time in forced swim, increased phosphorylation of hypothalamic adenosine monophosphate‐activated protein kinase (AMPK) and acetyl‐CoA carboxylase and a decreased concentration of hypothalamic malonyl‐CoA. Weight of the adrenal glands, locomotion in an OF, mitogen‐activated protein kinase cascade and calcium/calmodulin‐dependent protein kinases II in the hippocampus were not affected by chronic mild food restriction. Our findings suggest that chronic mild food restriction activates AMPK following a decreased hypothalamic malonyl‐CoA.     

Haematological and febrile response to Escherichia coli lipopolysaccharide in 12‐week‐old cockerels of genetically diverse layer lines fed diets with increasing L‐arginine levels

Due to its decisive function in the avian metabolic, endocrine and immune system L‐arginine (Arg) is dietary indispensable for chickens. In 12‐week‐old cockerels of two high‐ and two low‐performing purebred layer lines, the effects of increasing dietary Arg on the haematological and febrile response were studied over 48 h after single lipopolysaccharide (LPS) injection. The offered diets contained Arg equivalent to 70%, 100% and 200% of recommended supply. Pathophysiological alterations in weight gain, feed intake, body temperature and differential blood count were examined in comparison with their physiological initial values. Within the first 24 h after LPS injection, cockerels reduced feed intake and lost body weight subsequently. Thereby, low‐performing genotypes lost body weight to a lesser extent than high‐performing ones. The loss of body weight was further intensified by deficient dietary Arg. Within the following 24 h, cockerels recovered by improving feed intake and weight gain. Furthermore, LPS induced genotype‐specific fever response: both brown genotypes showed initial hypothermia followed by longer lasting moderate hyperthermia, whereas the white genotypes exhibited biphasic hyperthermia. Fever response was accompanied by significant changes in differential blood counts. Characterized by lymphopenia and heterophilia, a severe leucopenia was observed from 4 to 8 h after LPS injection and replaced by a marked leucocytosis with longer lasting monocytosis up to 48 h after LPS injection. Under given pathophysiological conditions, deficiently Arg‐supplied cockerels showed higher total leucocyte counts than adequately and excessively Arg‐supplied cockerels. However, deficient and surplus dietary Arg tended to cause higher ratios between heterophils and lymphocytes. To conclude, present results confirmed that LPS induced numerous immunological changes in 12‐week‐old cockerels and emphasized that chicken's genotype is a source of variation to be considered for immunological studies. Deficient dietary Arg intensified acute changes in differential blood counts and weight gain during LPS‐induced inflammation.     

The effect of dextromethorphan in preventing cholecalciferol-induced poison shyness and sickness-induced anorexia in the laboratory Norway rat

BACKGROUND: Overcoming bait and poison shyness is critical to the success of pest control operations against rats and other rodents. The authors hypothesized that the N-methyl-D-aspartate receptor blocker, dextromethorphan, could prevent the acquired memory of sickness and sickness-induced anorexia resulting from rodents eating poisoned bait. RESULTS: Cholecalciferol (1/4 LD(50)) was mixed with dextromethorphan and fed to rats on two 2 day sessions, with an 18 day break in between. Dextromethorphan did not prevent poison shyness; during the second poisoning period, both the cholecalciferol only and the cholecalciferol plus dextromethorphan groups had lower intakes of the bait compared with the control and dextromethorphan only groups. In addition to the previously recorded symptoms of cholecalciferol poisoning, the rats in this trial were observed to have nose bleeds, weepy eyes, laboured breathing and, in the case of the cholecalciferol only treated group, a period of decreased water intake followed by a period of increased water intake. There was also a period of increased water intake in the cholecalciferol plus dextromethorphan group.CONCLUSION: Dextromethorphan failed to prevent poison shyness and the anorectic effect of cholecalciferol. However, it did reduce anorexia from 17 days in the cholecaliferol group to 8 days in the cholecalciferol plus dextromethorphan group.     

Associations between Theileria orientalis Ikeda type infection and the growth rates and haematocrit of suckled beef calves in the North Island of New Zealand

AIMS: The principle aim of this study was to examine the association between infection with Theileria orientalis Ikeda type and growth rates of suckled beef calves on four beef farms. In addition, associations between calf sex, sampling time, and individual farm and T. orientalis Ikeda type infection intensity and haematocrit (HCT) were investigated.

METHODS: The study was a prospective longitudinal study in which 240 calves from four purposively selected beef farms in the North Island of New Zealand were blood sampled and weighed in late spring, mid-summer and early autumn. Two farms were from high-risk (A and B) and two from low-risk (C and D) tick areas. Blood samples were analysed to determine HCT, and the number of T. orientalis Ikeda type organisms/µL of blood (infection intensity) using a quantitative PCR assay. A calf was defined as infected if >415 organisms/µL were detected in a blood sample. Linear mixed models were used to examine associations between infection intensity, mean daily liveweight gain (MDG), HCT, calf sex and time of sampling on the four farms.

RESULTS: On Farms A and B nearly all calves were infected at each sampling time, on Farm C <30% were infected at any sampling and on Farm D infection prevalence increased from 32 to 79% between late spring and early autumn. On Farms C and D, from mid-summer to early autumn, mean MDG was 0.127 (95% CI=0.072–0.183) kg/day less for infected than uninfected calves (p<0.001). On all farms MDG was negatively associated with infection intensity for mid-summer and early autumn sampling times (p=0.037). The relationship between time of sampling and infection intensity varied between farms (p<0.001), and between male and female calves (p=0.018). Females had a higher infection intensity than males at the mid-summer and early autumn samplings. The association between HCT and infection intensity varied with sampling time and farm (p=0.018). There was a strong negative association between infection intensity and HCT at the late spring sampling, but in mid-summer there was no association, and in early autumn only a weak association.

CONCLUSIONS AND CLINICAL RELEVANCE: This study has shown that beef farmers in the North Island of New Zealand should be concerned about the welfare effects and economic impacts of T. orientalis Ikeda type infection in suckled beef calves.