| 1. |
- Astrand, Annika, et al.
(författare)
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Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity.
- 2004
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 287:4
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Tidskriftsartikel (refereegranskat)abstract
- Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1(-/-) mice demonstrated a significantly increased heart rate [24-h period: wild type 495 +/- 4 vs. MCHR1(-/-) 561 +/- 8 beats/min (P < 0.001); dark phase: wild type 506 +/- 8 vs. MCHR1(-/-) 582 +/- 9 beats/min (P < 0.001); light phase: wild type 484 +/- 13 vs. MCHR1(-/-) 539 +/- 9 beats/min (P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 +/- 0.3 vs. MCHR1(-/-) 113 +/- 0.4 mmHg (P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1(-/-) mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1(-/-) mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone.
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| 2. |
- Bohlooly-Yeganeh, Mohammad, 1966, et al.
(författare)
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Osteoporosis in MCHR1-deficient mice.
- 2004
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X. ; 318:4, s. 964-9
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Tidskriftsartikel (refereegranskat)abstract
- It is well recognized that the hypothalamus is of central importance in the regulation of food intake and fat mass. Recent studies indicate that it also plays an important role in the regulation of bone mass. Melanin concentrating hormone (MCH) is highly expressed in the hypothalamus and has been implicated in regulation of energy homeostasis. We developed MCHR1 inactivated mice to evaluate the physiological role of this receptor. Interestingly, the MCHR1(-/-) mice have osteoporosis, caused by a reduction in the cortical bone mass, while the amount of trabecular bone is unaffected. The reduction in cortical bone mass is due to decreased cortical thickness. Serum levels of c-telopeptide, a marker of bone resorption, are increased in MCHR1(-/-) mice, indicating that the MCHR1(-/-) mice have a high bone turnover osteoporosis. In conclusion, the MCHR1(-/-) mice have osteoporosis, indicating that MCHR1-signalling is involved in a tonic stimulation of bone mass.
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