Co‑administration with Obestatin Reduces Accumulation of Subcutaneous Fat Due to Rosiglitazone Administration in DIO‑C57BL/6 Mice.

It was observed previously that the gastro-peptide obestatin upregulated glycerolipid metabolism and PPARγ signalling in
normal Swiss albino mice. In this study, the role of obestatin and the combined role of obestatin and rosiglitazone: a PPARγ
agonist were assessed in diet-induced-obese C57BL/6 mice for their ability to reduce fat accumulation. Obesity was induced
by feeding 60% calorie by fat high fat diet for 25 weeks. 160 nmol/KgBW obestatin, 3 mg/KgBW of rosiglitazone and their
combination were administered intraperitoneally for eight days after induction of obesity. Decrease in food intake were
observed in case of obestatin and obestatin+rosiglitazone for a period of 6 h after administration. Rosiglitazone showed
increased gain in body weight. Whereas, obestatin and obestatin+rosiglitazone showed decrease in gain in body weight.
Rosiglitazone showed signifcant decrease in plasma triglycerides and free fatty acids by 50.93%, and 24.98% respectively.
The same decrease were retained upon co-administration with obestatin. Rosiglitazone showed increase in gluteal, cervical
and subcutaneous fat and total fat content by 60%, 17.8%, 12% and 20% respectively. Combined administration of obestatin
and rosiglitazone reduced all the rosiglitazone increased fat content of gluteal, cervical, subcutaneous and total fat to the
control group levels. Histopathology studies show signifcantly decreased adipocyte size in epididymal adipose tissue from
an average area of 250–4000 μm2
in the control to 250–1750 μm2
in the obestatin treated group and a further decrease to
250–1110 μm2
in the rosiglitazone treated group. Obestatin+rosiglitazone retained the reduction in average adipocyte area
similar to that of rosiglitazone. An increase in average cell size in inguinal adipose tissue from 250–2250 to 250–3000 μm2
was observed for both obestatin and rosiglitazone but a drastic increase to 250–4000 μm2
was observed for obestatin+rosiglitazone. Doubling of liver triglyceride content by rosiglitazone was decreased by 13.5% upon co-administration with obestatin.
These fndings indicate co-administration of obestatin and rosiglitazone retain all the favourable parameters and reduce fat
accumulation brought about by rosiglitazone.