*2.2.3. Otsuka Long-Evans Tokusima fatty (OLETF) rat*

Otsuka Long-Evans Tokushima fatty rats show an impaired glucose tolerance from 8 weeks of age, and the plasma glucose level becomes higher from 18 weeks of age [57]. In kidney of OLETF rats, pathological changes such as diffuse glomerulosclerosis and nodular lesion are observed [58]. The proliferation in mesangial cells is observed at 25 weeks of age, and the mesangial area enlargement is observed with extracellular matrix accumulation and GBM thickening after 40 weeks of age. Nodular-like lesions are observed after 65 weeks of age, and the lesions expand to the proliferated mesangial area. Tubular interstitial lesions, such as mononuclear cell filtration and fibrosis, are also observed. In the retinal capillaries after 56 weeks of age, the basement membranes are thicker, and the ratio of pericyte area decreases [59]. Regarding cataract, slight lens fiber swelling is observed in the anterior and/or posterior subcapsular regions at 40 weeks of age in OLETF rats [60]. In examination of peripheral nerve functions in OLETF rats, MNCV tends to decrease after about 40 weeks of age as compared with lean rats [61].

In NASH-like lesions of OLETF rats, there are some reports of MCD diet-induced steatohepatitis [62, 63]. The steatohepatitis is accelerated in OLETF rats after 8 weeks fed MCD diet. Furthermore, the MCD + HF diet leads to rapid development of precirrhosis in OLETF rats.
