Systemic homeostatic response to acute and subchronic high temperature housing in a CD-1 mouse model
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Background and Purpose: As global warming has accelerated in recent years; adverse human health consequences of high external temperature (T) have become a pressing issue. Birds and mammals have evolved to maintain core body T above that of the atmosphere. Increases in ambient T trigger physiological responses such as inhibition of shivering (skeletal muscle) and non-shivering thermogenesis (brown adipose tissue), and activation of sweating, salivation and vasodilation, in addition to behavioral adaptation – which are conserved across mammals. The goal of this study was to understand short and long-term physiological consequences of higher housing T that could impair health in a mouse model.
Methods: In a subchronic study, 7-8-wk-old male and female CD-1 mice were housed in T-controlled rooms within a vivarium suite. Male and female mice were housed in separate rooms. Room Ts were maintained either at ~ 22 oC (normal vivarium T) or at ~ 30-31 oC (high T). At wk 4, 8 and/or 12, animals were temporarily moved for assessment of body composition, behavior, cardiovascular function, and glucose/insulin tolerance (n=12/groupTo examine whether subchronic housing for 12 wk at elevated T modified the response to a subsequent acute thermal stress, animals were subjected to an acute heat stress at higher T of 37 oC. After wk 12 of housing at either 22 or 30-31 oC, CD-1 male and female mice were exposed to either 22 or 37 oC for 3 hours. Upon termination of exposure tissue samples were collected in a staggered manner within 2 hours (n=12/group).
Results: Mice housed at 30-31 oC demonstrated progressive weight gain (>10%) and increased body fat composition over 12 wks (both sexes) when compared to mice housed at 22 oC. Assessment of activity using open field test indicated small reduction in both sexes. Total cholesterol or HDL were not significantly changed by high T, but LDL and triglyceride levels increased at wk 8 and 12 (males>females) suggesting evidence of lipidemia. Food consumption measured during wk 10-11 was increased in males but not females. Fasting glucose clearance was impaired at wk 4, with exacerbation at wk 8 and persistent effect at wk 12 (males>females) in animals housed at high T. A small degree of insulin resistance was noted in both male and female mice housed at 30-31 oC. These metabolic changes were associated with dynamic changes in circulating stress hormone, corticosterone, which increased at week 4 but progressively reduced at wk 8 and wk 12. Acute heat exposure decreased body weight, produced hypoglycemia, and increased circulating free fatty acids as well as triglycerides in males and females of both subchronic T groups. However, only males had increased cholesterol and LDL at baseline due to subchronic high T housing, and acute heat stressor further exacerbated these changes. Acute heat stressor increased circulating neutrophils and produced lymphopenia in both male and female mice sub chronically housed at 22 or 30-31 oC, except for in females housed at 22 oC and subjected to acute heat stress.
Conclusions: These data show that subchronic heat exposure in CD-1 mice at near their thermoneutral zone (30-31 oC) is associated with marked weight gain, systemic metabolic alterations, glucose intolerance, insulin resistance and dampening of HPA response. These long-term adaptive physiological changes could reverse upon termination of exposure. However, homeostatic changes induced by subchronic heat exposure could intensify by episodic or continued heat exposure. This was evident by modified acute heat stress response in animals living at high T. Thus, high T exposures are associated with adaptive stress-mediated metabolic and immune cell alterations and stress hormone changes that are heat intensity-dependent.