Epidemiological and experimental evidence recognize a relationship between sleep-wake cycles and adiposity levels, but the mechanisms that link both are not entirely understood. Adipose tissue secretes adiponectin and leptin hormones, mainly involved as indicators of adiposity levels and recently associated to sleep. To understand how two of the main adipose tissue hormones could influence sleep-wake regulation, we evaluated in male rats, the effect of direct administration of adiponectin or leptin in the ventrolateral preoptic nuclei (VLPO), a major area for sleep promotion. The presence of adiponectin (AdipoR1 and AdipoR2) and leptin receptors in VLPO were confirmed by immunohistochemistry. Adiponectin administration increased wakefulness during the rest phase, reduced delta power, and activated wake-promoting neurons, such as the locus coeruleus (LC), tuberomammillary nucleus (TMN) and hypocretin/orexin neurons (OX) within the lateral hypothalamus (LH) and perifornical area (PeF). Conversely, leptin promoted REM and NREM sleep, including increase of delta power during NREM sleep, and induced c-Fos expression in VLPO and melanin concentrating hormone expressing neurons (MCH). In addition, a reduction in wake-promoting neurons activity was found in the TMN, lateral hypothalamus (LH) and perifornical area (PeF), including in the OX neurons. Moreover, leptin administration reduced tyrosine hydroxylase (TH) immunoreactivity in the LC. Our data suggest that adiponectin and leptin act as hormonal mediators between the status of body energy and the regulation of the sleep-wake cycle.

One of the hallmarks of the metabolic syndrome (MS) is the increase of renal sympathetic nerve activity (RSNA), which leads to the upregulation of the renin‐angiotensin system (RAS). Interestingly, the sympathetic hyperactivity in the kidney of obese humans often occurs in absence of overt systemic hypertension. The stimulation of RSNA contributes to the glomerular lesions and the progressive loss of nephron functionality, resulting in acute renal injury (AKI) and, in the long term, chronic kidney disease (CKD), which represent the most common complication of MS. Clinical evidence and animal models of MS have shown that renal sympathetic denervation (RSDN) induces a transient attenuation of the hypertensive symptoms, while the markers of kidney damage continue worsening. Therefore, it is likely that the renal derangement in MS might also depend on the metabolic impairment, such as the upregulation of plasma leptin and insulin, independently from the RSNA. To investigate this issue, we explored the effect of MS over blood pressure and kidney functionality, in intact and renal denervated rats. For that, animals were either fed with a standard diet (SD) or a high‐fat diet for 12 weeks (HFD), with or without bilateral renal denervation performed at the beginning of protocol (n = 6). Results indicate that, as expected, HFD in intact animals promotes fat accumulation, glucose intolerance and hypertension, but also decreases water consumption and induces marked proteinuria from week 7, slight hematuria from week 9, with respect to SD rats. Remarkably, the renal denervation prevents the changes that HFD triggered in blood pressure and renal parameters only in the short and medium term, but it is ineffective in the long term. On the bases of these results, we suggest that the hypertension associated to MS is not only due to hyperactivation of RSNA, but it could involve hormonal/hemodynamic factors, typical of metabolic impairment, which could contribute to renal injury.Support or Funding InformationCONACYT‐CB‐243298This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.