Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood.
We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system (RAS) is expressed and functional in the white adipose tissue (WAT) and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass) or saline, starting at the first day of life until the age of 16 days. Between days ninetieth and hundred and eightieth, a group of these animals received high fat diet (HFD). Molecular, biochemical, histological, and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight, and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) gene expression in hypothalamus, fatty acid synthase (FAS), and hormone-sensitive lipase (HSL) gene expression in retroperitoneal WAT, and decreases peroxixome proliferators-activated receptor (PPAR)γ, PPARα, uncoupling protein (UCP)2, and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood.
School of Environmental and Biological Science, Universidade Federal da Grande Dourados Dourados, Brazil.
Kely
K
de Picoli Souza
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Elton D
ED
da Silva
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Elice C
EC
Batista
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Felipe C G
FC
Reis
Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Sylvia M A
SM
Silva
Department of Rheumatology, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Charlles H M
CH
Castro
Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Jaqueline
J
Luz
Department of Physiology and Biophysics, Universidade Federal de Minas Gerais Belo Horizonte, Brazil.
Jorge L
JL
Pesquero
School of Environmental and Biological Science, Universidade Federal da Grande Dourados Dourados, Brazil.
Edson L
EL
Dos Santos
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
João B
JB
Pesquero
NPY; PPAR; UCP; hyperphagia; overweight; renin-angiotensin system