The Role of Obesity in Obstructive Sleep Apnea (OSA)

Intermittent Hypoxia and Leptins

Scott Mesenger recently published a Master's Thesis that implicates compelling links between Leptin Signaling and OSA: http://ir.lib.uwo.ca/cgi/viewcontent.cgi?article=2487&context=etd. This work was done in the John Cirello Lab at University of Western Ontario. The study extensively uses our Ob-Rb Antibody to generate data.

There is a strong link between obesity and OSA. "Perhaps the single most important factor affecting OSA risk is body weight. Weight gain of 10% increases the risk of developing OSA by six-fold (Peppard et al., 2000a) and a 10% loss of body weight is estimated to decrease the apnea/hypopnea index (events/hour) by 26%  Within the obese population (BMI ≥ 30) (Wolk et al., 2003), approximately 40% experience significant OSA and approximately 70% of OSA patients are obese (Vgontzas et al., 1994), daunting numbers considering the obesity epidemic occurring in North America and estimates suggesting 41% of Americans will be obese by 2015 (Nejat et al., 2009)."

"Leptin can exert cardiovascular effects by acting centrally, as has been shown by studies introducing leptin directly into the CNS. Central administration serves to increase plasma catecholamines epinephrine and norepinephrine (Satoh et al., 1999). In other studies, leptin has been found to increase SNA, arterial pressure as well as heart rate and to inhibit the baroreflex (Arnold et al., 2009; Mark et al., 2009). Leptin may also have a role in modulating the peripheral chemoreflex at the level of the CNS as microinjection of leptin into caudal pressor areas of the NTS has been found to potentiate the sympathetic and blood pressure responses to chemoreflex activation (Ciriello & Moreau, 2012). These cardiovascular effects may not be debilitating under normal homeostatic conditions, however in conditions of increased circulating leptin, such as in OSA and obesity, the cardiovascular responses may be detrimental."

This study shows the increase in the expression of leptins like Ob-Rb in Carotid .

Images: Fluorescent (a-c) photomicrographs showing the effect of IH on Ob-Rb (a) and ERK 1/2 (b) expression in carotid body glomus cells. Note that Ob-Rb and ERK 1/2 are co-expressed in the same cells (c). Calibration mark in (a) represents 100 μm and applies to (a-c).

Images: Western blots showing the presence of Ob-Rb (a) and Ob-R100 (b) in carotid bodies after IH. Note that IH significantly (*) decreases the protein level of Ob-Rb (a), while significantly (*) increasing the protein level of Ob-R100 (b) compared to normoxic controls (b). p values are indicated. n=5-6.

This study will give the reader great insights on the molecular biology of OSA. Check it out: http://ir.lib.uwo.ca/cgi/viewcontent.cgi?article=2487&context=etd.