Altered Upper Airway and Soft Tissue Structures in the New Zealand Obese Mouse

Abstract

Rationale: The effect of obesity on upper airway soft tissue structure and size was examined in the New Zealand Obese (NZO) mouse and in a control lean mouse, the New Zealand White (NZW). Objectives: We hypothesized that the NZO mouse has increased volume of neck fat and upper airway soft tissues and decreased pharyngeal airway caliber. Methods: Pharyngeal airway size, volume of the upper airway soft tissue structures, and distribution of fat in the neck and body were measured using magnetic resonance imaging (MRI). Dynamic MRI was used to examine the differences in upper airway caliber between inspiration and expiration in NZO versus NZW mice. Measurements and Main Results:The data support the hypothesis that, in obese NZO versus lean NZW mice, airway caliber was significantly smaller (P , 0.03), with greater parapharyngeal fat pad volumes (P , 0.0001) and a greater volume of other upper airway soft tissue structures (tongue, P 5 0.003; lateral pharyngeal walls, P 5 0.01; soft palate, P 5 0.02). Dynamic MRI showed that the airway of the obese NZO mouse dilated during inspiration, whereas in the lean NZW mouse, the upper airway was reduced in size during inspiration. Conclusions: In addition to the increased volume of pharyngeal soft tissue structures, direct fat deposits within the tongue may contribute to airway compromise in obesity. Pharyngeal airway dilation during inspiration in NZO mice compared with narrowing in NZW mice suggests that airway compromise in obese mice may lead to muscle activation to defend upper airway patency during inspiration.

Rodent models of sleep apnea

“…Since obesity is a major risk factor for obstructive sleep apnea, the upper airway of obese mice has been characterized using imaging and physiologic approaches. Volumetric MRI assessment in the obese New Zealand mouse demonstrated a phenotype of increased visceral fat, neck fat, and increased volume of the tongue, soft palate, and lateral pharyngeal walls compared to lean mice (Brennick et al, 2009). Additionally, leptin-deficient ob/ob mice have defects in upper airway neuromechanical control which is reversed with leptin administration (Polotsky et al, 2012), which suggests that leptin protects against upper airway obstruction in obese mice, and that mice deficient in leptin may be vulnerable to the development of obstructive apnea.…”

Inhaled aerosol particle dosimetry in mice: A review

“…The cross-sectional area of the nasal pharynx and its bend angle are important parameters that will affect particle deposition in this area. Limited quantitative data is available for the pharyngeal region of the New Zealand white mouse (Brennick et al, 2009). These investigators found that the dynamic cross-sectional area of the pharyngeal airways of an obese mouse model is significantly smaller than the lean counterpart, which can influence particle deposition in this area and have repercussions for subsequent particle deposition in the larynx, TB, and P region.…”

Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles

“…Among upper airway muscles that are innervated by hypoglossal motoneurons (XIImns) (Dobbins and Feldman, 1995; Altshuler et al, 1994; Saboisky et al, 2007; Fregosi and Ludlow, 2014), the genioglossus (GG) muscle is the most important dilator because its activation increases airway caliber (Remmers et al, 1978; Brennick et al, 2009). The activity of both XIImns and GG muscle is reduced during non-rapid eye movement (NREM) sleep and it is further suppressed during rapid eye movement (REM) sleep (Sauerland and Harper, 1976; Suratt et al, 1988; Horner et al, 1989; Richard and Harper, 1991; Mezzanotte et al, 1992; Katz and White, 2004; Saboisky et al, 2007; Eckert et al, 2009).…”