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[Characteristics of lipolysis in epididymal adipose tissues of OLETF rats with spontaneous type 2 diabetic mellitus].

OBJECTIVE
To observe the characteristics of lipolysis in epididymal adipose tissues of spontaneously type 2 diabetic animal model-Otsuka Long-Evans Tokushima Fatty (OLETF) rats-in different stages of disease and explore the possible molecular mechanism.


METHODS
We adopted OLETF rats as subjects, and Long-Evans Tokushima Otsuka (LETO) rats were used as age-matched normal controls. Oral glucose tolerance tests (OGTT) and fasting serum insulin levels were performed respectively at the ages of 8, 18 and 28 weeks. The animals were sacrificed and epididymal fat pads were obtained in corresponding weeks. Glycerol released in the culture medium was determined by use of a colorimetric assay and served as an index of lipolysis. The protein levels of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), perilipin, extracellular signal-regulated kinase (ERK) and its phosphorylated form (p-ERK) in epididymal fat were examined by immunoblotting.


RESULTS
(1) Compared with the age-matched normal control, the ratio of epididymal adipose tissues to total body weight was heavier at the end of 18 weeks [(1.80±0.09)% vs (1.23±0.07)%, P<0.01] and 28 weeks [(2.51±0.12)% vs (1.56±0.08)%, P<0.01]; In OGTT 1 h plasma glucose levels of OLETF rats were higher at the age of 18 weeks [(26.00±3.09) vs (10.50±0.82) mmol/L, P<0.01] and 28 weeks [(23.15±0.55) vs (9.72±0.17) mmol/L, P<0.01] and 2 h plasma glucose levels were higher at the age of 18 weeks [(16.19±1.22) vs (7.47±0.35) mmol/L, P<0.01] and 28 weeks [(17.96±2.00) vs (9.24±0.47) mmol/L, P<0.01]. The level of fasting insulin was higher in OLETF rats than that of LETO rats only at the age of 28 weeks [(68.17±13.35)×10(-3) vs (19.61±0.20)×10(-3) U/L, P<0.01]. (2) Glycerol released from epididymal adipose tissues of OLETF rats was increased by 34.7% compared with LETO rats at the age of 18 weeks [(213.0±12.5) vs (158.2±11.7) nmol/(g×h), P<0.05], whereas at the age of 28 weeks, it was reduced by 33.5% [(210.2±37.8) vs (315.9±25.0) nmol/(g×h), P<0.05]. (3) In OLETF rats, HSL protein level was not altered at the age of 18 weeks, but down-regulated at the age of 28 weeks. Nevertheless, the expressions of ATGL and perilipin were decreased, while p-ERK protein expression was increased at the age of both 18 and 28 weeks.


CONCLUSION
With the development of disease in spontaneously type 2 diabetic animal model of OLETF rats, the lipolysis in epididymal adipose tissue presented a pattern of initial increase followed by subsequent reduction. The earlier augment may contribute to the higher expression of p-ERK and the lower content of perilipin, however the later decrease may result from the reduction of both HSL and ATGL level.