An isoflavone cladrin prevents high-fat diet-induced bone loss and inhibits the expression of adipogenic gene regulators in 3T3-L1 adipocyte.
OBJECTIVE
This study evaluates the effect of isoflavone cladrin on high-fat diet (HFD)-induced bone loss and adipogenesis.


METHODS
Thirty-two 4-week-old male C57BL/6J mice were divided into four groups: a standard diet group, a HFD group and HFD group with cladrin (5 and 10 mg/kg per day orally) for 12 weeks. The effect of cladrin on bone micro-architecture, bone marrow cell lineages and hyperlipidaemia were assessed. For assessing anti-adipogenic activity of cladrin, 3T3-L1 cells were used.


RESULTS
Cladrin attenuated HFD-induced hyperlipidaemia and bone loss by preserving bone micro-architecture and strength. Effect of cladrin was found at the level of bone marrow progenitor cells. Gene expression profile of cladrin-treated mice bone showed upregulation of osteoblast and downregulation of adipogenic transcription factors and increased OPG/RANKL ratio. Cladrin inhibited cellular lipid accumulation through downregulation of transcription factors such as PPAR-γ and C/EBP-α and modulated the expression of major adipokines involved behind obesity stimulation without eliciting cell cytotoxicity in 3T3-L1 adipocytes.


CONCLUSIONS
We conclude that cladrin may improve obesity-induced bone loss and hyperlipidaemia in mice fed HFD and adipogenesis in 3T3-L1 cells by modifying adipokines and could offer clinical benefits as a supplement to treat obesity-induced disorders.
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Jyoti
J
Gautam
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Vikram
V
Khedgikar
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Dharmendra
D
Choudhary
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Priyanka
P
Kushwaha
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
Preeti
P
Dixit
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Divya
D
Singh
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
Rakesh
R
Maurya
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, India.
Ritu
R
Trivedi
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D031290:Butea / Q000737:chemistry; D059305:Diet, High-Fat / Q000009:adverse effects*; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control; D053244:Osteoprotegerin / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D053245:RANK Ligand / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D054392:Adipokines; D007529:Isoflavones; D053244:Osteoprotegerin; D048789:Phytoestrogens; D010936:Plant Extracts; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors; C558945:cladrin
adipokine; high-fat diet; hyperlipidaemia; isoflavone