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Three Merino ewes, adapted for about 3 weeks to their environment, were bled at 10 min intervals through a jugular venous cannula. Radioimmunoassay of plasma samples for cortisol revealed marked diurnal variations with peak levels just after midnight and lowest values in the afternoon. This rhythm appeared to result from a changing amplitude associated with a distinct ultradian rhythm (frequency 0·8–1·2 cycles/h) in the plasma level of cortisol. Calculation of the daily rate of secretion of cortisol from the hormone profiles gave a mean value of 8·49 mg. Arguments are put forward in favour of this method for obtaining the true rate of secretion of cortisol.
Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Gibbett Hill Road, Coventry CV4 7AL, UK
Warwickshire Nuffield Hospital, Leamington Spa, Warwickshire, CV32 6RW, UK
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Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Gibbett Hill Road, Coventry CV4 7AL, UK
Warwickshire Nuffield Hospital, Leamington Spa, Warwickshire, CV32 6RW, UK
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Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Gibbett Hill Road, Coventry CV4 7AL, UK
Warwickshire Nuffield Hospital, Leamington Spa, Warwickshire, CV32 6RW, UK
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Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Gibbett Hill Road, Coventry CV4 7AL, UK
Warwickshire Nuffield Hospital, Leamington Spa, Warwickshire, CV32 6RW, UK
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Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Gibbett Hill Road, Coventry CV4 7AL, UK
Warwickshire Nuffield Hospital, Leamington Spa, Warwickshire, CV32 6RW, UK
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Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Gibbett Hill Road, Coventry CV4 7AL, UK
Warwickshire Nuffield Hospital, Leamington Spa, Warwickshire, CV32 6RW, UK
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Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression was detected in subcutaneous (s.c.) and omental adipose tissue and in isolated adipocytes. Protein for OX1R and OX2R was also detected in whole adipose tissue sections and lysates. Treatment with orexin-A, and orexin-B (100 nM, 24 h) resulted in a significant increase in peroxisome proliferator-activated receptors γ-2 mRNA expression in s.c. adipose tissue (P < 0.05). Hormone sensitive lipase mRNA was significantly reduced in omental adipose tissue with orexin-A and orexin-B treatment (P < 0.05). Glycerol release from omental adipose tissue was also significantly reduced with orexin-A treatment (P < 0.05).
These findings demonstrate for the first time the presence of functional orexin receptors in human adipose tissue and suggest a role for orexins in adipose tissue metabolism and adipogenesis.
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The synthetic compound NO-1886 (ibrolipim) is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides. Recently, we found that NO-1886 also reduced plasma free fatty acids and glucose in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 treatment on ectopic lipid deposition and the islet pathology in miniature swine fed a high-fat/high-sucrose diet. Our results showed that feeding this diet to miniature swine caused insulin resistance, increased lipid deposition in non-adipose tissue, such as in the heart, skeletal muscle, liver and pancreas, and also caused pancreatic beta cell damage. However, supplementing 1% NO-1886 (200 mg/kg per day) into the high-fat/high-sucrose diet decreased ectopic lipid deposition, improved insulin resistance, and alleviated the beta cell damage. These results suggest that improvement of lipid disorder, non-adipose tissue steatosis and insulin resistance may be very important for the protection of beta cell damage. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistance syndrome.
