Bilirubin reduces visceral obesity and insulin resistance by suppression of inflammatory cytokines

Autor: Motoyuki Kohjima, Tomoaki Inoue, Ryuichi Sakamoto, Yoshihiro Ogawa, Ryoko Takei, Noriyuki Sonoda, Misato Okamoto, Toyoshi Inoguchi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Physiology
Adipose tissue
Pathology and Laboratory Medicine
Biochemistry
Fats
Mice
chemistry.chemical_compound
Endocrinology
0302 clinical medicine
Animal Cells
Adipocyte
Adipocytes
Medicine and Health Sciences
Insulin
Bile
Immune Response
Connective Tissue Cells
Multidisciplinary
Middle Aged
Lipids
Body Fluids
Adipose Tissue
Physiological Parameters
Connective Tissue
Obesity
Abdominal
Cytokines
Medicine
Female
Inflammation Mediators
Anatomy
Cellular Types
Bioelectrical impedance analysis
Research Article
medicine.medical_specialty
Endocrine Disorders
Bilirubin
Science
Immunology
030209 endocrinology & metabolism
Intra-Abdominal Fat
Proinflammatory cytokine
03 medical and health sciences
Signs and Symptoms
Insulin resistance
Diagnostic Medicine
Diabetes mellitus
Internal medicine
Diabetes Mellitus
medicine
Animals
Humans
Obesity
Aged
Inflammation
Endocrine Physiology
Triglyceride
business.industry
Body Weight
NADPH Oxidases
Biology and Life Sciences
Cell Biology
medicine.disease
Biological Tissue
030104 developmental biology
chemistry
Metabolic Disorders
Insulin Resistance
business
Biomarkers
Zdroj: PLoS ONE, Vol 14, Iss 10, p e0223302 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: Objective Although previous studies have reported a negative relationship between serum bilirubin concentration and the development of diabetes mellitus (DM), the relationship between bilirubin and insulin resistance has not been thoroughly assessed. This study was designed to determine the relationships between bilirubin, body fat distribution, and adipose tissue inflammation in patients with type 2 DM and the effect of bilirubin in an obese animal model. Method Body fat distribution was measured using an abdominal dual bioelectrical impedance analyzer in patients with type 2 DM. We also measured glycemic control, lipid profile, serum bilirubin concentration and other clinical characteristics, and determined their relationships with body fat distribution. In the animal study, biliverdin (20 mg/kg daily) was orally administered to high-fat diet (HFD)-induced obese (DIO) mice for 2 weeks, after which intraperitoneal insulin tolerance testing was performed. Then, adipocyte area, adipocytokine expression, and macrophage polarization were evaluated in epididymal adipose tissues. Results In the clinical study, univariate analysis showed that a lower bilirubin concentration was significantly correlated with higher body mass index, waist circumference, triglyceride, uric acid, creatinine, visceral fat area and lower HDL-C. In multivariate analyses, bilirubin concentration significantly correlated with diastolic blood pressure, creatinine, and visceral fat area. However, there was no association between bilirubin concentration and subcutaneous fat area. In the animal study, DIO mice treated with biliverdin had smaller adipocytes than untreated DIO mice and biliverdin improved HFD-induced insulin resistance. Biliverdin treatment reversed the higher gene expression of Cd11c, encoding an M1 macrophage marker, and Tnfa, encoding the proinflammatory cytokine tumor necrosis factor-α, in the adipose tissues of DIO mice. These data suggest biliverdin administration alleviates insulin resistance by ameliorating inflammation and the dysregulation of adipocytokine expression in adipose tissues of DIO mice. Conclusions Bilirubin may protect against insulin resistance by ameliorating visceral obesity and adipose tissue inflammation.
Databáze: OpenAIRE
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