title: Grape skin extract protects against programmed changes in the adult rat offspring caused by maternal high-fat diet during lactation.
abstract: Maternal overnutrition during suckling period is associated with increased risk of metabolic disorders in the offspring. We aimed to assess the effect of Vitis vinifera L. grape skin extract (ACH09) on cardiovascular and metabolic disorders in adult male offspring of rats fed a high-fat (HF) diet during lactation. Four groups of female rats were fed: control diet (7% fat), ACH09 (7% fat plus 200 mg kg(-1) d(-1) ACH09 orally), HF (24% fat), and HF+ACH09 (24% fat plus 200 mg kg(-1) d(-1) ACH09 orally) during lactation. After weaning, all male offspring were fed a control diet and sacrificed at 90 or 180 days old. Systolic blood pressure was increased in adult offspring of HF-fed dams and ACH09 prevented the hypertension. Increased adiposity, plasma triglyceride, glucose levels and insulin resistance were observed in offspring from both ages, and those changes were reversed by ACH09. Expression of insulin cascade proteins IRS-1, AKT and GLUT4 in the soleus muscle was reduced in the HF group of both ages and increased by ACH09. The plasma oxidative damage assessed by malondialdehyde levels was increased, and nitrite levels decreased in the HF group of both ages, which were reversed by ACH09. In addition, ACH09 restored the decreased plasma and mesenteric arteries antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase in the HF group. In conclusion, the treatment of HF-fed dams during lactation with ACH09 provides protection from later-life hypertension, body weight gain, insulin resistance and oxidative stress. The protective effect ACH09 may involve NO synthesis, antioxidant action and activation of insulin-signaling pathways.
authors.affiliation: Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil. Electronic address: angelacr@uerj.br.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Resende
authors.forename: Andréa F
authors.initials: AF
authors.lastname: Emiliano
authors.forename: Viviane S C
authors.initials: VS
authors.lastname: Cordeiro
authors.forename: Graziele F
authors.initials: GF
authors.lastname: de Bem
authors.forename: Lenize C R M
authors.initials: LC
authors.lastname: de Cavalho
authors.forename: Paola Raquel B
authors.initials: PR
authors.lastname: de Oliveira
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Neto
authors.forename: Cristiane A
authors.initials: CA
authors.lastname: Costa
authors.forename: Gilson T
authors.initials: GT
authors.lastname: Boaventura
authors.forename: Roberto S
authors.initials: RS
authors.lastname: de Moura
mesh_terms: D050154:Adiposity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002374:Catalase / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005638:Fruit / Q000737:chemistry; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D007774:Lactation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D039382:Maternal Nutritional Physiological Phenomena; D008659:Metabolic Diseases / Q000517:prevention & control; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D014280:Triglycerides / Q000097:blood; D027843:Vitis / Q000737:chemistry*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010936:Plant Extracts; C495694:Slc2a4 protein, rat; D014280:Triglycerides; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D051058:Oncogene Protein v-akt
keywords: Developmental programming; Grape skin extract; Hypertension; Insulin resistance; Oxidative stress