Oral Presentation ANZOS-OSSANZ-AOCO Joint Annual Scientific Meeting 2017

Characterising the metabolic phenotype in adolescent inhalant abuse: long-term changes to energy balance independent of food intake (#185)

Rose Crossin 1 , Andrew J Lawrence 1 2 , Brian Oldfield 3 , Aneta Stefanidis 3 , Zane B Andrews 3 , Jhodie R Duncan 1 4
  1. Florey Insititute of Neuroscience and Mental Health, Parkville, VIC, Australia
  2. Florey Department of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
  3. Monash Obesity and Diabetes Institute, Monash University, Melbourne, VIC, Australia
  4. School of Medicine, University of Adelaide, Adelaide, SA, Australia

Background:

Abuse of products containing toluene (e.g. glue sniffing) primarily occurs during adolescence and has been associated with symptoms such as appetite suppression and impaired weight gain. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and the persistence of this phenotype during abstinence remains unknown.

Adolescent male Wistar rats (PND 27) were exposed to inhaled toluene (10,000ppm) (n=42) or air (n=48) for 1 hour/day, 3 days/week for 4 weeks, followed by 4 weeks abstinence. 20 air-rats were pair-fed to the toluene group, to differentiate the direct effects of inhaled toluene from malnutrition on metabolism. Food and water intake, weight and growth were monitored. Appetite signalling hormones were measured, after both the last exposure and abstinence, and during an insulin tolerance test. Energy expenditure was measured using metabolic cages and adipose tissue assays.

Results:

Toluene-exposure suppressed appetite by up to 26% (p<0.001). Reduced weight gain (p<0.001) and growth (p=0.001) were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, toluene rats’ weight or growth did not normalise in abstinence (p=0.001), despite normalisation of food consumption. Toluene-exposure increased metabolic rate (p=0.035), energy expenditure (p=0.028), thermogenesis in adipose tissue (p=0.005), and altered substrate utilisation (p=0.024). After 4 weeks’ exposure, toluene rats had decreased fasting blood glucose (p=0.022) and decreased fasting insulin (p=0.005) compared to both air and pair-fed groups, and increased insulin sensitivity (p=0.003).

Conclusions:

Toluene-exposure results in a hypermetabolic phenotype, which persists during abstinence. Our results suggest a long-term alteration of growth set-points, independent of food intake, which includes altered glucose regulation. Whilst the underlying mechanism of this phenotype is the focus of future studies, our findings demonstrate that the metabolic consequences of inhalant abuse may affect the health of individuals beyond the time of active substance abuse.