Carbenoxolone Treatment Ameliorated Metabolic Syndrome in WNIN/Ob Obese Rats, but Induced Severe Fat Loss and Glucose Intolerance in Lean Rats

Autor: Vijay Kumar Prathipati, Swarupa Rani Koppala, Harishankar Nemani, Mahesh Sukapaka, Siva Sankara Vara Prasad Sakamuri, Giridharan Nappan Veetill, Vajreswari Ayyalasomayajula, Shailaja Pothana, Lakshmi Raj Kumar Ponday, Vani Acharya, Uday Kumar Putcha
Rok vydání: 2012
Předmět:
Male
Anatomy and Physiology
medicine.medical_treatment
lcsh:Medicine
Adipose tissue
Biochemistry
Eating
chemistry.chemical_compound
Corticosterone
11-beta-Hydroxysteroid Dehydrogenase Type 1
Adrenal Glands
Adipocytes
Enzyme Inhibitors
lcsh:Science
Metabolic Syndrome
Multidisciplinary
Chemistry
Fatty liver
Organ Size
Lipids
Adipose Tissue
Liver
Body Composition
Carbenoxolone
Medicine
Glycogen
hormones
hormone substitutes
and hormone antagonists
Glucocorticoid
Signal Transduction
Research Article
medicine.drug
medicine.medical_specialty
Immunology
Endocrine System
Insulin resistance
Thinness
Internal medicine
Glucose Intolerance
medicine
Animals
Obesity
Biology
Triglycerides
Nutrition
Diabetic Endocrinology
Inflammation
Insulin
Cholesterol
HDL
lcsh:R
Immunity
Hypertrophy
Lipid Metabolism
medicine.disease
Fibrosis
Rats
Metabolism
Endocrinology
Gene Expression Regulation
Metabolic Disorders
lcsh:Q
Metabolic syndrome
Zdroj: PLoS ONE, Vol 7, Iss 12, p e50216 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: BACKGROUND: 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX) on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. METHODOLOGY/PRINCIPAL FINDINGS: Subcutaneous injection of CBX (50 mg/kg body weight) or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment). Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. CONCLUSIONS/SIGNIFICANCE: We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions.
Databáze: OpenAIRE
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