Organotins in obesity and associated metabolic disturbances

Alexey A. Tinkov, Olga P. Ajsuvakova, Margarita G. Skalnaya, Anatoly V. Skalny, Michael Aschner, Joanna Suliburska, Jan Aaseth

Research output: Contribution to journalReview article

Abstract

The objective of the present study was to review the mechanisms of organotin-induced adipogenesis, obesity, and associated metabolic disturbances. Peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα) activation is considered as the key mechanism of organotin-induced adipogenesis. Particularly, organotin exposure results in increased adipogenesis both in cell and animal models. Moreover, transgenerational inheritance of organotin-induced obese phenotype was demonstrated in vivo. At the same time, the existing data demonstrate that organotin compounds (OTCs) induces aberrant expression of PPARγ-targeted genes, resulting in altered of adipokine, glucose transporter, proinflammatory cytokines levels, and lipid and carbohydrate metabolism. The latter is generally characterized by hyperglycemia and insulin resistance. Other mechanisms involved in organotin-induced obesity may include estrogen receptor and corticosteroid signaling, altered DNA methylation, and gut dysfunction. In addition to cellular effects, organotin exposure may also affect neural circuits of appetite regulation, being characterized by neuropeptide Y (NPY) up-regulation in parallel with of pro-opiomelanocortin (POMC), Agouti-related protein (AgRP), and cocaine and amphetamine regulated transcript (CART) down-regulation in the arcuate nucleus. These changes result in increased orexigenic and reduced anorexigenic signaling, leading to increased food intake. The existing data demonstrate that organotins are potent adipogenic agents, however, no epidemiologic studies have been performed to reveal the association between organotin exposure and obesity and the existing indirect human data are contradictory.

LanguageEnglish (US)
Pages49-59
Number of pages11
JournalJournal of Inorganic Biochemistry
Volume191
DOIs
StatePublished - Feb 1 2019

Fingerprint

Adipogenesis
PPAR gamma
Agouti-Related Protein
Obesity
Retinoid X Receptor alpha
Organotin Compounds
Pro-Opiomelanocortin
Adipokines
Facilitative Glucose Transport Proteins
Neuropeptide Y
Amphetamine
Cocaine
Estrogen Receptors
Appetite Regulation
Adrenal Cortex Hormones
Arcuate Nucleus of Hypothalamus
Animals
Genes
Chemical activation
Carbohydrate Metabolism

Keywords

  • Adipogenesis
  • Adipose tissue
  • Organotin
  • PPARγ
  • RXRα

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Tinkov, A. A., Ajsuvakova, O. P., Skalnaya, M. G., Skalny, A. V., Aschner, M., Suliburska, J., & Aaseth, J. (2019). Organotins in obesity and associated metabolic disturbances. Journal of Inorganic Biochemistry, 191, 49-59. https://doi.org/10.1016/j.jinorgbio.2018.11.002

Organotins in obesity and associated metabolic disturbances. / Tinkov, Alexey A.; Ajsuvakova, Olga P.; Skalnaya, Margarita G.; Skalny, Anatoly V.; Aschner, Michael; Suliburska, Joanna; Aaseth, Jan.

In: Journal of Inorganic Biochemistry, Vol. 191, 01.02.2019, p. 49-59.

Research output: Contribution to journalReview article

Tinkov, AA, Ajsuvakova, OP, Skalnaya, MG, Skalny, AV, Aschner, M, Suliburska, J & Aaseth, J 2019, 'Organotins in obesity and associated metabolic disturbances' Journal of Inorganic Biochemistry, vol. 191, pp. 49-59. https://doi.org/10.1016/j.jinorgbio.2018.11.002
Tinkov, Alexey A. ; Ajsuvakova, Olga P. ; Skalnaya, Margarita G. ; Skalny, Anatoly V. ; Aschner, Michael ; Suliburska, Joanna ; Aaseth, Jan. / Organotins in obesity and associated metabolic disturbances. In: Journal of Inorganic Biochemistry. 2019 ; Vol. 191. pp. 49-59.
@article{55edeb8c262c4917b6a1c6d5c540bcc8,
title = "Organotins in obesity and associated metabolic disturbances",
abstract = "The objective of the present study was to review the mechanisms of organotin-induced adipogenesis, obesity, and associated metabolic disturbances. Peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα) activation is considered as the key mechanism of organotin-induced adipogenesis. Particularly, organotin exposure results in increased adipogenesis both in cell and animal models. Moreover, transgenerational inheritance of organotin-induced obese phenotype was demonstrated in vivo. At the same time, the existing data demonstrate that organotin compounds (OTCs) induces aberrant expression of PPARγ-targeted genes, resulting in altered of adipokine, glucose transporter, proinflammatory cytokines levels, and lipid and carbohydrate metabolism. The latter is generally characterized by hyperglycemia and insulin resistance. Other mechanisms involved in organotin-induced obesity may include estrogen receptor and corticosteroid signaling, altered DNA methylation, and gut dysfunction. In addition to cellular effects, organotin exposure may also affect neural circuits of appetite regulation, being characterized by neuropeptide Y (NPY) up-regulation in parallel with of pro-opiomelanocortin (POMC), Agouti-related protein (AgRP), and cocaine and amphetamine regulated transcript (CART) down-regulation in the arcuate nucleus. These changes result in increased orexigenic and reduced anorexigenic signaling, leading to increased food intake. The existing data demonstrate that organotins are potent adipogenic agents, however, no epidemiologic studies have been performed to reveal the association between organotin exposure and obesity and the existing indirect human data are contradictory.",
keywords = "Adipogenesis, Adipose tissue, Organotin, PPARγ, RXRα",
author = "Tinkov, {Alexey A.} and Ajsuvakova, {Olga P.} and Skalnaya, {Margarita G.} and Skalny, {Anatoly V.} and Michael Aschner and Joanna Suliburska and Jan Aaseth",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.jinorgbio.2018.11.002",
language = "English (US)",
volume = "191",
pages = "49--59",
journal = "Journal of Inorganic Biochemistry",
issn = "0162-0134",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Organotins in obesity and associated metabolic disturbances

AU - Tinkov, Alexey A.

AU - Ajsuvakova, Olga P.

AU - Skalnaya, Margarita G.

AU - Skalny, Anatoly V.

AU - Aschner, Michael

AU - Suliburska, Joanna

AU - Aaseth, Jan

PY - 2019/2/1

Y1 - 2019/2/1

N2 - The objective of the present study was to review the mechanisms of organotin-induced adipogenesis, obesity, and associated metabolic disturbances. Peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα) activation is considered as the key mechanism of organotin-induced adipogenesis. Particularly, organotin exposure results in increased adipogenesis both in cell and animal models. Moreover, transgenerational inheritance of organotin-induced obese phenotype was demonstrated in vivo. At the same time, the existing data demonstrate that organotin compounds (OTCs) induces aberrant expression of PPARγ-targeted genes, resulting in altered of adipokine, glucose transporter, proinflammatory cytokines levels, and lipid and carbohydrate metabolism. The latter is generally characterized by hyperglycemia and insulin resistance. Other mechanisms involved in organotin-induced obesity may include estrogen receptor and corticosteroid signaling, altered DNA methylation, and gut dysfunction. In addition to cellular effects, organotin exposure may also affect neural circuits of appetite regulation, being characterized by neuropeptide Y (NPY) up-regulation in parallel with of pro-opiomelanocortin (POMC), Agouti-related protein (AgRP), and cocaine and amphetamine regulated transcript (CART) down-regulation in the arcuate nucleus. These changes result in increased orexigenic and reduced anorexigenic signaling, leading to increased food intake. The existing data demonstrate that organotins are potent adipogenic agents, however, no epidemiologic studies have been performed to reveal the association between organotin exposure and obesity and the existing indirect human data are contradictory.

AB - The objective of the present study was to review the mechanisms of organotin-induced adipogenesis, obesity, and associated metabolic disturbances. Peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα) activation is considered as the key mechanism of organotin-induced adipogenesis. Particularly, organotin exposure results in increased adipogenesis both in cell and animal models. Moreover, transgenerational inheritance of organotin-induced obese phenotype was demonstrated in vivo. At the same time, the existing data demonstrate that organotin compounds (OTCs) induces aberrant expression of PPARγ-targeted genes, resulting in altered of adipokine, glucose transporter, proinflammatory cytokines levels, and lipid and carbohydrate metabolism. The latter is generally characterized by hyperglycemia and insulin resistance. Other mechanisms involved in organotin-induced obesity may include estrogen receptor and corticosteroid signaling, altered DNA methylation, and gut dysfunction. In addition to cellular effects, organotin exposure may also affect neural circuits of appetite regulation, being characterized by neuropeptide Y (NPY) up-regulation in parallel with of pro-opiomelanocortin (POMC), Agouti-related protein (AgRP), and cocaine and amphetamine regulated transcript (CART) down-regulation in the arcuate nucleus. These changes result in increased orexigenic and reduced anorexigenic signaling, leading to increased food intake. The existing data demonstrate that organotins are potent adipogenic agents, however, no epidemiologic studies have been performed to reveal the association between organotin exposure and obesity and the existing indirect human data are contradictory.

KW - Adipogenesis

KW - Adipose tissue

KW - Organotin

KW - PPARγ

KW - RXRα

UR - http://www.scopus.com/inward/record.url?scp=85056645103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056645103&partnerID=8YFLogxK

U2 - 10.1016/j.jinorgbio.2018.11.002

DO - 10.1016/j.jinorgbio.2018.11.002

M3 - Review article

VL - 191

SP - 49

EP - 59

JO - Journal of Inorganic Biochemistry

T2 - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

SN - 0162-0134

ER -