Anatomy and Neuroscience - Research Publications

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    The effect of adolescent inhalant abuse on energy balance and growth
    Crossin, R ; Qama, A ; Andrews, ZB ; Lawrence, AJ ; Duncan, JR (JOHN WILEY & SONS LTD, 2019-08-01)
    The abuse of volatile solvents such as toluene is a significant public health concern, predominantly affecting adolescents. To date, inhalant abuse research has primarily focused on the central nervous system; however, inhalants also exert effects on other organ systems and processes, including metabolic function and energy balance. Adolescent inhalant abuse is characterized by a negative energy balance phenotype, with the peak period of abuse overlapping with the adolescent growth spurt. There are multiple components within the central and peripheral regulation of energy balance that may be affected by adolescent inhalant abuse, such as impaired metabolic signaling, decreased food intake, altered dietary preferences, disrupted glucose tolerance and insulin release, reduced adiposity and skeletal density, and adrenal hypertrophy. These effects may persist into abstinence and adulthood, and the long-term consequences of inhalant-induced metabolic dysfunction are currently unknown. The signs and symptoms resulting from chronic adolescent inhalant abuse may result in a propensity for the development of adult-onset metabolic disorders such as type 2 diabetes, however, further research investigating the long-term effects of inhalant abuse upon energy balance and metabolism are needed. This review addresses several aspects of the short- and long-term effects of inhalant abuse relating to energy and metabolic processes, including energy balance, intake and expenditure; dietary preferences and glycemic control; and the dysfunction of metabolic homeostasis through altered adipose tissue, bone, and hypothalamic-pituitary-adrenal axis function.
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    Chronic intermittent toluene inhalation in adolescent rats results in metabolic dysfunction with altered glucose homeostasis
    Dick, ALW ; Simpson, A ; Qama, A ; Andrews, Z ; Lawrence, AJ ; Duncan, JR (WILEY, 2015-11-01)
    BACKGROUND AND PURPOSE: Abuse 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 4 weeks of abstinence. Metabolic hormones and GTT were subsequently measured. KEY RESULTS: Adolescent 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 IMPLICATIONS: CIT exposure during adolescence has long-term effects on metabolic function, which may increase the risk of disorders related to energy balance and glycaemic control.