Dietary obacunone supplementation stimulates muscle hypertrophy, and suppresses hyperglycemia and obesity through the TGR5 and PPARγ pathway

Journal Article · Fri Aug 07 04:00:00 EDT 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.06.022· OSTI ID:22462150

Horiba, Taro ^[1]; Katsukawa, Masahiro ^[1]; Mita, Moeko; Sato, Ryuichiro ^[2]

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1. Research and Development Division, Kikkoman Corporation, Chiba (Japan)
2. Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo (Japan)

Obacunone is a limonoid that is predominantly found in Citrus. Although various biological activities of limonoids have been reported, little is known about the beneficial effects of obacunone on metabolic disorders. In the present study, we examined the effects of dietary obacunone supplementation on obese KKAy mice, to clarify the function of obacunone in metabolic regulation. Mice were pair-fed a normal diet either alone or supplemented with 0.1% w/w obacunone for 28 days. Compared with the control, obacunone-fed mice had lower glycosylated hemoglobin, blood glucose, and white adipose tissue weight, although there was no significant difference in body weight. Obacunone treatment also significantly increased the weight of the gastrocnemius and quadriceps muscles. Reporter gene assays revealed that obacunone stimulated the transcriptional activity of the bile acids-specific G protein-coupled receptor, TGR5, in a dose-dependent manner. In addition, obacunone inhibited adipocyte differentiation in 3T3-L1 cells and antagonized ligand-stimulated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. These results suggest that obacunone stimulates muscle hypertrophy and prevents obesity and hyperglycemia, and that these beneficial effects are likely to be mediated through the activation of TGR5 and inhibition of PPARγ transcriptional activity. - Highlights: • Citrus limonoid obacunone prevents hyperglycemia in obese, diabetic KKAy mice. • Obacunone reduces fat content and stimulates muscle hypertrophy in KKAy mice. • Obacunone stimulates TGR5 transcriptional activities. • Obacunone antagonizes PPARγ and inhibits lipid accumulation in adipocytes.

• OSTI ID: 22462150
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 463; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
BILE ACIDS
BLOOD
CITRUS
DIET
FATS
GENES
GLUCOSE
GTP-ASES
HEMOGLOBIN
HYPERGLYCEMIA
HYPERTROPHY
LIPIDS
METABOLIC DISEASES
MICE
MUSCLES
RECEPTORS
WEIGHT