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• W2777268342 abstract "Although central melanocortin 4 receptor (MC4R) blockade abolishes the central nervous system (CNS)-mediated anorexogenic, antidiabetic, and cardiovascular actions of leptin, chronic MC4R stimulation fails to completely mimic the effects of leptin. Because neuropeptide Y (NPY) and MC4R exert opposite effects on cardiovascular and metabolic functions, we tested the role of NPY in offsetting the long-term actions of MC4R activation. Wild-type (WT) and NPY-deficient (NPY −/− ) mice were implanted with telemetry probes for measuring mean arterial pressure (MAP) and heart rate (HR) 24 h/day. After the mice recovered from surgery and stable baseline measurements, the MC3/4R agonist melanotan II (MTII, 120 μg·kg −1 ·day −1 iv) was infused for 7 days followed by a recovery period. No major differences between groups were observed at baseline except for slightly higher food intake and HR in NPY −/− mice (4.3 ± 0.2 vs. 3.4 ± 0.2 g/day and 567 ± 14 vs. 522 ± 13 beats/min). Chronic MTII infusion reduced food intake in both groups while causing transient increases in MAP and HR only in WT mice (peaks of 11 ± 3 mmHg and 126 ± 13 beats/min). To examine whether NPY deficiency would amplify the antidiabetic effects of MC4R activation, diabetes was induced with streptozotocin (STZ) 1 wk before baseline measurements were taken, and the same experimental protocol was followed. In WT and NPY −/− mice, STZ-induced diabetes led to similar hyperphagia, hyperglycemia, and weight loss, which were not reversed by chronic MTII treatment. Our results demonstrate that chronic MC4R activation, even in NPY-deficient mice, does not mimic chronic antidiabetic, cardiovascular, or metabolic actions of leptin, and that NPY is not essential for hyperphagia or cardiovascular changes associated with diabetes." @default.
• W2777268342 created "2018-01-05" @default.
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• W2777268342 date "2018-04-01" @default.
• W2777268342 modified "2023-10-16" @default.
• W2777268342 title "Control of appetite, blood glucose, and blood pressure during melanocortin-4 receptor activation in normoglycemic and diabetic NPY-deficient mice" @default.
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• W2777268342 doi "https://doi.org/10.1152/ajpregu.00293.2017" @default.
• W2777268342 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5966815" @default.
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