Agouti Revisited: Transcript Quantification of the ASIP Gene in Bovine Tissues Related to Protein Expression and Localization

Beside its role in melanogenesis, the agouti signaling protein (ASIP) has been related to obesity. The potentially crucial role in adipocyte development makes it a tempting candidate for economic relevant, fat related traits in farm animals. The objective of our study was to characterize the mRNA expression of different ASIP transcripts and of putative targets in different bovine tissues, as well as to study consequences on protein abundance and localization. ASIP mRNA abundance was determined by RT-qPCR in adipose and further tissues of cattle representing different breeds and crosses. ASIP mRNA was up-regulated more than 9-fold in intramuscular fat of Japanese Black cattle compared to Holstein (p<0.001). Further analyses revealed that a transposon-derived transcript was solely responsible for the increased ASIP mRNA abundance. This transcript was observed in single individuals of different breeds indicating a wide spread occurrence of this insertion at the ASIP locus in cattle. The protein was detected in different adipose tissues, skin, lung and liver, but not in skeletal muscle by Western blot with a bovine-specific ASIP antibody. However, the protein abundance was not related to the observed ASIP mRNA over-expression. Immuno-histochemical analyses revealed a putative nuclear localization of ASIP additionally to the expected cytosolic signal in different cell types. The expression of melanocortin receptors (MCR) 1 to 5 as potential targets for ASIP was analyzed by RT-PCR in subcutaneous fat. Only MC1R and MC4R were detected indicating a similar receptor expression like in human adipose tissue. Our results provide evidence for a widespread expression of ASIP in bovine tissues at mRNA and, for the first time, at protein level. ASIP protein is detectable in adipocytes as well as in further cells of adipose tissue. We generated a basis for a more detailed investigation of ASIP function in peripheral tissues of various mammalian species

Spatial pricing, optimal location and social welfare with consumer arbitrage

R32, R38,

Incentive consistency and the choice of a spatial pricing mode

D42, R10, R48,

Metabolic factors and blood cancers among 578,000 adults in the metabolic syndrome and cancer project (Me-Can)

We investigated associations between metabolic factors and blood cancer subtypes. Data on body mass index (BMI), blood pressure, blood glucose, total cholesterol, and triglycerides from seven prospective cohorts were pooled (n = 578,700; mean age = 44 years). Relative risks of blood cancers were calculated from Cox regression models. During mean follow-up of 12 years, 2,751 incident and 1,070 fatal cases of blood cancers occurred. Overall, higher BMI was associated with an increased blood cancer risk. In gender-specific subgroup analyses, BMI was positively associated with blood cancer risk (p = 0.002), lymphoid neoplasms (p = 0.01), and Hodgkin's lymphoma (p = 0.02) in women. Further associations with BMI were found for high-grade B-cell lymphoma (p = 0.02) and chronic lymphatic leukemia in men (p = 0.05) and women (p = 0.01). Higher cholesterol levels were inversely associated with myeloid neoplasms in women (p = 0.01), particularly acute myeloid leukemia (p = 0.003), and glucose was positively associated with chronic myeloid leukemia in women (p = 0.03). In men, glucose was positively associated with risk of high-grade B-cell lymphoma and multiple myeloma, while cholesterol was inversely associated with low-grade B-cell lymphoma. The metabolic syndrome score was related to 48 % increased risk of Hodgkin's lymphoma among women. BMI showed up as the most consistent risk factor, particularly in women. A clear pattern was not found for other metabolic factors