title: Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats.
abstract: Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.
authors.affiliation: Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.
authors.forename: K R
authors.initials: KR
authors.lastname: Cantelli
authors.affiliation: Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.
authors.forename: G M
authors.initials: GM
authors.lastname: Soares
authors.affiliation: Universidade Federal do Rio de Janeiro, Macaé, RJ, Brasil.
authors.forename: R A
authors.initials: RA
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.
authors.forename: S L
authors.initials: SL
authors.lastname: Balbo
authors.affiliation: Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: C
authors.initials: C
authors.lastname: Lubaczeuski
authors.affiliation: Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: A C
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.
authors.forename: A C F
authors.initials: AC
authors.lastname: Araújo
authors.affiliation: Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.
authors.forename: M L
authors.initials: ML
authors.lastname: Bonfleur
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood; D004386:Duodenum / Q000601:surgery*; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D005234:Fatty Liver / Q000378:metabolism* / Q000503:physiopathology; D015390:Gastric Bypass / Q000379:methods*; D007027:Hypothalamic Diseases / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism* / Q000503:physiopathology; D007583:Jejunum / Q000601:surgery*; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D054890:Fatty Acid Synthase, Type I