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Abstract:
Background and PurposeAbuse of toluene-containing inhalants is an
increasing public health problem, especially among adolescents. Abuse
during adolescence is associated with emaciation, while industrial
exposure leads to altered glycaemic control suggesting metabolic
instability. However, the relationship between adolescent inhalant abuse
and metabolic dysfunction remains unknown.
EXPERIMENTAL APPROACH To model human abuse patterns, we exposed male
adolescent Wistar rats [ postnatal day ( PND) 27] to chronic
intermittent inhaled toluene ( CIT, 10 000 ppm) or air ( control) for 1
h . day(-1), three times a week for 4 weeks. Feeding and body
composition were monitored. After 4 weeks, circulating metabolic hormone
concentrations and responses to a glucose tolerance test (GTT) were
measured. Dietary preference was measured by giving animals access to
either a `western diet' plus standard chow ( WC + SC) or standard chow
alone during 4weeks of abstinence. Metabolic hormones and GTT were
subsequently measured.
Key ResultsAdolescent CIT exposure significantly retarded weight gain,
altered body composition, circulating metabolic hormones and responses
to a GTT. While reduced body weight persisted, responses to a GTT and
circulating hormones appeared to normalize for animals on standard chow
following abstinence. In CIT-exposed WC+SC rats, we observed impaired
glucose tolerance associated with altered metabolic hormones. Analysis
of hypothalamic genes revealed differential expression profiles in
CIT-exposed rats following both the exposure period and abstinence,
suggesting a central contribution to inhalant-induced metabolic
dysfunction.
Conclusion and ImplicationsCIT exposure during adolescence has long-term
effects on metabolic function, which may increase the risk of disorders
related to energy balance and glycaemic control.
