title: Early and Long-term Undernutrition in Female Rats Exacerbates the Metabolic Risk Associated with Nutritional Rehabilitation.
abstract: Human studies have suggested that early undernutrition increases the risk of obesity, thereby explaining the increase in overweight among individuals from developing countries who have been undernourished as children. However, this conclusion is controversial, given that other studies do not concur. This study sought to determine whether rehabilitation after undernutrition increases the risk of obesity and metabolic disorders. We employed a published experimental food-restriction model. Wistar female rats subjected to severe food restriction since fetal stage and controls were transferred to a moderately high-fat diet (cafeteria) provided at 70 days of life to 6.5 months. Another group of undernourished rats were rehabilitated with chow. The energy intake of undernourished animals transferred to cafeteria formula exceeded that of the controls under this regime and was probably driven by hypothalamic disorders in insulin and leptin signal transduction. The cafeteria diet resulted in greater relative increases in both fat and lean body mass in the undernourished rats when compared with controls, enabling the former group to completely catch up in length and body mass index. White adipose tissues of undernourished rats transferred to the high-lipid regime developed a browning which, probably, contributed to avoid the obesigenic effect observed in controls. Nevertheless, the restricted group rehabilitated with cafeteria formula had greater accretion of visceral than subcutaneous fat, showed increased signs of macrophage infiltration and inflammation in visceral pad, dyslipidemia, and ectopic fat accumulation. The data indicate that early long-term undernutrition is associated with increased susceptibility to the harmful effects of nutritional rehabilitation, without causing obesity.
authors.affiliation: From the Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain, the Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029 Spain, and.
authors.forename: Esther
authors.initials: E
authors.lastname: Lizárraga-Mollinedo
authors.affiliation: the Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029 Spain, and.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fernández-Millán
authors.affiliation: the Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: García-San Frutos
authors.affiliation: From the Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: de Toro-Martín
authors.affiliation: the Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Fernández-Agulló
authors.affiliation: the Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ros
authors.affiliation: From the Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain, the Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029 Spain, and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Álvarez
authors.affiliation: From the Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain, the Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029 Spain, and fescriva@farm.ucm.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Escrivá
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D002149:Energy Intake; D005260:Female; D006963:Hyperphagia / Q000209:etiology / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D044342:Malnutrition / Q000150:complications* / Q000378:metabolism / Q000534:rehabilitation; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D010084:Oxidation-Reduction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D017208:Rats, Wistar; D012307:Risk Factors
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin
keywords: adipose tissue; hypothalamus; insulin; leptin; nutrition; undernutrition