Circulating levels of the cytokines IL10, IFNγ and resistin in an obese mouse model of developmental programming.

An infant's early developmental environment plays a pivotal role in the programming of its physiological phenotype. The identification of the factors in the maternal environment that mediate the effects of maternal obesity and diet is essential to the development of clinical intervention strategies. Maternal hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, hyperleptinaemia and altered inflammatory cytokines concentrations are potentially important predictive factors of her future offspring's susceptibility to metabolic disease. Using a diet-induced obese mouse model, we have investigated which of these maternal factors could induce adverse metabolic programming in the offspring. Female C57Bl/6 mice were fed either laboratory chow (10% fat) or high fat diet (42% fat) for 10 weeks before mating and throughout gestation. At day 18 of pregnancy, maternal body weight, body composition and glucose tolerance were measured, as well as plasma insulin, adiponectin, RBP4, leptin, resistin and the inflammatory cytokines (IL6, IL10, IL12, IL1ß, IFNγ, KC, TNF-α). At day 18 of pregnancy, high fat-fed dams were significantly heavier than the chow dams and had increased fat mass. High fat-fed dams had higher 5 h fasting blood glucose than chow dams and elevated plasma insulin. Although the obese dams had both reduced plasma adiponectin and resistin levels compared with lean dams, their plasma IL6, IL10 and IFNγ levels were all increased. High fat feeding in pregnancy leads to altered plasma concentrations of both adipokines and adipocytokines in the dam that may directly pass to the fetus and affect their development.

Leanness in postnatally nutritionally programmed rats is associated with increased sensitivity to leptin and a melanocortin receptor agonist and decreased sensitivity to neuropeptide Y.

BACKGROUND: Pups of normally nourished dams that are cross-fostered after birth to dams fed a low-protein (8% by weight) diet (postnatal low protein (PLP)) grow slower during the suckling period and remain small and lean throughout adulthood. At weaning, they have increased expression in the arcuate nucleus (ARC) of the hypothalamus of the orexigenic neuropeptide Y (NPY) and decreased expression of pro-opiomelanocortin, the precursor of anorexigenic melanocortins. OBJECTIVES AND METHODS: We investigated, using third ventricle administration, whether 3-month-old male PLP rats display altered sensitivity to leptin with respect to food intake, NPY and the melanocortin 3/4-receptor agonist MTII, and using in situ hybridization or laser capture microdissection of the ARC followed by RT-PCR, whether the differences observed were associated with changes in the hypothalamic expression of NPY or the leptin receptor, NPY receptors and melanocortin receptors. RESULTS: PLP rats were smaller and had reduced percentage body fat content and plasma leptin concentration compared with control rats. Leptin (5 µg) reduced food intake over 0-48 h more in PLP than control rats (P<0.05). Submaximal doses of NPY increased the food intake less in PLP rats than in controls, whereas submaximal doses of MTII reduced the food intake more in PLP rats. Maximal responses did not differ between PLP and control rats. Leptin and melanocortin-3 receptor (MC3R) expression were increased in both ARC and ventromedial hypothalamic nuclei in PLP animals compared with the controls. MC4R, NPY Y1R, Y5R and NPY expression were unchanged. CONCLUSION: Postnatal undernourishment results in food intake in adult rats being more sensitive to reduction by leptin and melanocortins, and less sensitive to stimulation by NPY. We propose that this contributes to increased leptin sensitivity and resistance to obesity. Increased expression of ObRb and MC3R may partly explain these findings but other downstream mechanisms must also be involved.

Eosinophilic fasciitis: a good response with conservative treatment.

A 52 year old man developed progressive painful swelling of both calves and difficulty walking. Physical examination showed asymmetrical localised swelling with induration and tenderness on palpation. Peripheral blood eosinophilia was noted. Biopsy of deep fascia and muscle showed typical features of eosinophilic fasciitis. He was treated with non-steroidal anti-inflammatory drugs and intensive physiotherapy. The clinical features had completely resolved six months later.