Impairment of the serotonergic control of feeding in adult female rats exposed to intra-uterine malnutrition.
We have previously shown that adult female rats exposed to intra-uterine malnutrition were normophagic, although obese and resistant to insulin-induced hypophagia. The present study aimed at examining aspects of another important catabolic component of energy homeostasis control, the hypothalamic serotonergic function, which inhibits feeding and stimulates energy expenditure. Pregnant dams were fed ad libitum or were restricted to 50 % of ad libitum intake during the first 2 weeks of pregnancy. Control and restricted 4-month-old progeny were studied. The restricted rats had increased body adiposity with normal daily food intake but failed to respond with hypophagia to an intracerebroventricular injection of serotonin (5-hydroxytryptamine; 5-HT). Stimulation, by food ingestion, of extracellular levels of serotonin in medial hypothalamus microdialysates was more pronounced and lasted longer in the restricted than in the control rats. In the restricted group, hypothalamic levels of 5-HT 2C receptor protein tended to be reduced (P = 0.07) while the levels of 5-HT1B receptor and serotonin transporter proteins were significantly elevated (36 and 79 %, respectively). In conclusion, female rats undernourished in utero had normophagic obesity as adults but had an absence of serotonin-induced hypophagia and low hypothalamic levels of the 5-HT 2C receptor. Compensatory adaptations for the functional serotonergic impairment were evidenced, such as an enhanced release of serotonin in response to a meal allied to up-regulated hypothalamic 5-HT1B and transporter expression. Whether these compensations will persist in later life warrants further investigation. Moreover, it cannot be ruled out that the serotonergic component of energy expenditure was already impaired, thus contributing to the observed body-fat phenotype.
Pôrto
Laura C J
LC
Departamento de Fisiologia, Disciplina de Fisiologia da Nutrição, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Sardinha
Fátima L C
FL
Telles
Mônica M
MM
Guimarães
Regina B
RB
Albuquerque
Kelse T
KT
Andrade
Iracema S
IS
Oyama
Lila M
LM
Nascimento
Cláudia M O
CM
Santos
Oscar F P
OF
Ribeiro
Eliane B
EB
D000818:Animals; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D005315:Fetal Diseases / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism; D044342:Malnutrition / Q000503:physiopathology*; D017551:Microdialysis / Q000379:methods; D009765:Obesity / Q000196:embryology* / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*
D012701:Serotonin