Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring.
Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (+10%, P<0.05), visceral fat mass (+12%, P<0.05), and cross-sectional area of adipocytes (epididymal: +12% and inguinal: +43%, P<0.05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (-24%, P<0.05) and higher insulinemia (+56%, P<0.05), insulin resistance index (+43%, P<0.05), leptinemia (+113%, P<0.05), and leptin:adiponectin ratio (+98%, P<0.05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): -61%, janus tyrosine kinase 2: -41%, and p-signal transducer and activator of transcription 3: -56%, P<0.05), but higher suppressor of cytokine signaling 3 (+81%, P<0.05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.
de Oliveira
Elaine
E
Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Moura
Egberto G
EG
Santos-Silva
Ana Paula
AP
Pinheiro
Cíntia R
CR
Lima
Natalia S
NS
Nogueira-Neto
José Firmino
JF
Nunes-Freitas
Andre L
AL
Abreu-Villaça
Yael
Y
Passos
Magna C F
MC
Lisboa
Patrícia C
PC
D017667:Adipocytes / Q000473:pathology; D052242:Adiponectin / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D003367:Cotinine / Q000032:analysis / Q000097:blood; D004351:Drug Resistance; D005260:Female; D006003:Glycogen / Q000032:analysis; D006706:Homeostasis; D006984:Hypertrophy; D007031:Hypothalamus / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007774:Lactation; D020738:Leptin / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry; D008297:Male; D008892:Milk / Q000737:chemistry; D018482:Muscle, Skeletal / Q000737:chemistry; D009538:Nicotine / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood; D051381:Rats; D015398:Signal Transduction
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D009538:Nicotine; D006003:Glycogen; D003367:Cotinine