Is poor sleep associated with obesity in older adults? A narrative review of the literature.

INTRODUCTION: To address the worldwide epidemic of obesity, a sizable literature implicates sleep problems in the onset of obesity in younger populations. However, less is known about how this process may operate among older adults, which is of concern, given demographic shifts that have resulted in a much higher proportion of developed nations around the world reaching late life. METHODS: We offer a current review of the literature studying older adults and examining associations between sleep quality and obesity in this population. We consider both subjective and objectively measured sleep as well as both cross-sectional and longitudinal studies offering stronger causal inference. RESULTS: We discuss seemingly contradictory literature showing that shorter sleep duration as well as longer sleep duration are associated with obesity risk, then review studies that tested for non-linear relationships and reported a U-shape pattern, suggesting that too much or too little sleep is detrimental. Besides sleep duration, we discuss evidence showing that other forms of sleep dysfunction related to night-time awakenings, REM sleep, slow-wave sleep, and daytime sleepiness, which are indicators of sleep quality, are also linked to obesity. Specific psychological and physiological mediators and moderators, suggesting possible mechanisms whereby sleep problems may affect obesity in older adults, are described. CONCLUSION: We conclude by discussing areas, where additional research could help clarify this association, considering such factors as medical comorbidities common in late life, and health-related behaviors that may stem from poor sleep (such as disordered eating behavior). Such insights will have great value for clinical practice. LEVEL OF EVIDENCE: Level V, narrative review.

In-vivo administration of CLC-K kidney chloride channels inhibitors increases water diuresis in rats: a new drug target for hypertension?

OBJECTIVE: The human kidney-specific chloride channels ClC-Ka (rodent ClC-K1) and ClC-Kb (rodent ClC-K2) are important determinants of renal function, participating to urine concentration and blood pressure regulation mechanisms. Here we tested the hypothesis that these chloride channels could represent new drug targets for inducing diuretic and antihypertensive effects. METHODS: To this purpose, the CLC-K blockers benzofuran derivatives MT-189 and RT-93 (10, 50, 100 mg/kg), were acutely administered by gavage in Wistar rats, and pharmacodynamic and pharmacokinetic parameters determined by functional, bioanalytical, biochemical and molecular biology assays. RESULTS: Plasma concentration values for MT-189 and RT-93 were indicative of good bioavailability. Both MT-189 and RT-93 dose-dependently increased urine volume without affecting electrolyte balance. A comparable reduction of SBP was observed in rats after MT-189, RT-93 or furosemide administration. Benzofuran derivatives treatment did not affect kidney CLC-K mRNA level or inner medulla osmolality, whereas a significant vasopressin-independent down-regulation of aquaporin water channel type 2 was observed at protein and transcriptional levels. In rats treated with benzofuran derivatives, the observed polyuria was mainly water diuresis; this finding indirectly supports a cross-talk between chloride and water transport in nephron. Moreover, preliminary in-vitro evaluation of the drugs capability to cross the blood-inner ear barrier suggests that these compounds have a limited ability to induce potential auditory side effects. CONCLUSION: CLC-K blockers may represent a new class of drugs for the treatment of conditions associated with expanded extracellular volume, with a hopeful high therapeutic potential for hypertensive patients carrying ClC-K gain-of-function polymorphisms.