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Braz J Med Biol Res. 2017 Mar 30;50(5):e5858. doi: 10.1590/1414-431X20175858.

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats.

Author information

1
Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.
2
Universidade Federal do Rio de Janeiro, Macaé, RJ, Brasil.
3
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brasil.
4
Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brasil.

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.

PMID:
28380195
PMCID:
PMC5423738
DOI:
10.1590/1414-431X20175858
[Indexed for MEDLINE]
Free PMC Article
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