Global trends in the prevalence of overweight and obesity put the adipocyte in the focus of huge medical interest. This review highlights a new topic in adipose tissue biology, namely the emerging pathogenic role of fat accumulation in bone marrow (BM). Specifically, we summarize current knowledge about the origin and function of BM adipose tissue (BMAT), provide evidence for the association of excess BMAT with diabetes and related cardiovascular complications, and discuss potential therapeutic approaches to correct BMAT dysfunction. There is still a significant uncertainty about the origins and function of BMAT, although several subpopulations of stromal cells have been suggested to have an adipogenic propensity. BM adipocytes are higly plastic and have a distinctive capacity to secrete adipokines that exert local and endocrine functions. BM adiposity is abundant in elderly people and has therefore been interpreted as a component of the whole-body ageing process. BM senescence and BMAT accumulation has been also reported in patients and animal models with Type 2 diabetes, being more pronounced in those with ischaemic complications. Understanding the mechanisms responsible for excess and altered function of BMAT could lead to new treatments able to preserve whole-body homeostasis.

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet. 2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E 2 . 3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake. 4. The kallikrein–kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.

1. Activation of inactive renin in rat plasma has been studied with different trypsin concentrations and incubation times at pH 6.2 and 4°C. 2. Trypsin concentrations below 2 mg/ml, lower than endogenous rat plasma anti-trypsin activity, do not activate inactive renin, whereas maximal activation is obtained with trypsin at 6 mg/ml for 1 min at 4°C, pH 6.2. 3. Under these conditions trypsin can cleave dialysable fragments from renin substrate. ANG I can be generated at 37°C with a pH optimum of 5.3. Nevertheless, the ANG I formation at pH 6.2 was totally unaffected. 4. Incubations longer than 2 min with trypsin at 6 mg/ml can induce a direct cleavage of dialysable ANG I-containing fragments strongly interfering with the measurements of renin activity at pH 6.2. 5. On average 40% of the total renin measured in plasma of normotensive WK rats is in the inactive form, although a wide range of variation is observed.

1. Plasma samples from 31 normal subjects were treated (at 4°C, pH 7.0, for 2 min) with different concentrations of trypsin (500, 1000, 2000, 3000 and 4000 μg/ml) in order to assess which concentration yielded the maximum activation of inactive renin. 2. Endogenous antitryptic activity was also measured in all samples; the mean value ± sd (in μg of trypsin inhibited by 1 ml of plasma) was 953 ± 550 μg/ml (range 34–1800 μg/ml). 3. In the entire group of subjects the values of trypsin-activated renin measured with trypsin at 2000 μg/ml were significantly higher than those obtained with lower or higher trypsin concentrations. 4. With subjects divided into subgroups according to their endogenous anti-tryptic activity, the maximum yield of activation was reached with trypsin at 2000 μg/ml. 5. No significant correlations were found between single values of active, inactive or trypsin-activated renin and the corresponding levels of endogenous anti-tryptic activity. However, a weak but significant correlation ( r = 0.39, P < 0.05) was found between single values of anti-tryptic activity and the corresponding percentage of activation of inactive renin. 6. Thus the maximum activation of inactive renin at 4°C for 2 min is obtained with trypsin at 2000 μg/ml independently of the corresponding endogenous anti-tryptic activity. It is not excluded that the content of protease inhibitors in human plasma might affect the proportion in vivo of circulating active and inactive renin.