Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments

Rose Crossin, Zane B. Andrews, Natalie A. Sims, Terence Pang, Michael Mathai, Jonathan H. Gooi, Aneta Stefanidis, Brian J. Oldfield, Andrew J. Lawrence, Jhodie R. Duncan

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.

Original languageEnglish
Pages (from-to)340-354
Number of pages15
JournalNeuroendocrinology
Volume107
Issue number4
DOIs
Publication statusPublished - 2018

Keywords

  • Abstinence
  • Adrenal insufficiency
  • Hypo-cortisolism
  • Negative energy balance
  • Toluene
  • Volatile solvent abuse

Cite this

Crossin, Rose ; Andrews, Zane B. ; Sims, Natalie A. ; Pang, Terence ; Mathai, Michael ; Gooi, Jonathan H. ; Stefanidis, Aneta ; Oldfield, Brian J. ; Lawrence, Andrew J. ; Duncan, Jhodie R. / Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments. In: Neuroendocrinology. 2018 ; Vol. 107, No. 4. pp. 340-354.
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title = "Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments",
abstract = "Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.",
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author = "Rose Crossin and Andrews, {Zane B.} and Sims, {Natalie A.} and Terence Pang and Michael Mathai and Gooi, {Jonathan H.} and Aneta Stefanidis and Oldfield, {Brian J.} and Lawrence, {Andrew J.} and Duncan, {Jhodie R.}",
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Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments. / Crossin, Rose; Andrews, Zane B.; Sims, Natalie A.; Pang, Terence; Mathai, Michael; Gooi, Jonathan H.; Stefanidis, Aneta; Oldfield, Brian J.; Lawrence, Andrew J.; Duncan, Jhodie R.

In: Neuroendocrinology, Vol. 107, No. 4, 2018, p. 340-354.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic phenotype with persistent growth impairments

AU - Crossin, Rose

AU - Andrews, Zane B.

AU - Sims, Natalie A.

AU - Pang, Terence

AU - Mathai, Michael

AU - Gooi, Jonathan H.

AU - Stefanidis, Aneta

AU - Oldfield, Brian J.

AU - Lawrence, Andrew J.

AU - Duncan, Jhodie R.

PY - 2018

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N2 - Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.

AB - Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.

KW - Abstinence

KW - Adrenal insufficiency

KW - Hypo-cortisolism

KW - Negative energy balance

KW - Toluene

KW - Volatile solvent abuse

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