Time Course of Fat Accumulation in Various Organs of Young OLETF Rats

Abstract

PurposeExcessive fat accumulation induces chronic inflammation in the white adipose tissue (WAT), which leads and accelerates to obesity‐related health problems such as glucose intolerance, insulin resistance, and dyslipidemia. Determination of the time course of fat accumulation in obesity might allow identification of target tissues to treat the health problems in each stage. The purpose of the present study was to investigate the relationship between inflammatory changes and time course of fat accumulation in various organs.MethodsMale Otsuka Long‐Evans Tokushima fatty (OLETF) rats were used as spontaneous obesity animals. All rats were fed a standard diet containing 55.3% carbohydrate and water ad libitum. From 4‐ to 20‐week‐old, blood samples from vena cava and samples of the epididymal adipose tissue, retroperitoneal adipose tissue, mesenteric adipose tissue, and inguinal subcutaneous adipose tissue as WAT, brown adipose tissue (BAT) from interscapular region, liver, pancreas, and plantaris muscles were analyzed histologically every 2 weeks. Collected serum was used to detect triglyceride (TG) and free fatty acid (FFA) concentrations. Tissue samples were sliced and stained with hematoxylin and eosin or oil red O for histological observation.ResultsBody weight in OLETF rats increased linearly from 4‐ to 20‐week‐old. Although the wet weight and adipocyte diameter of the epididymal adipose tissue also increased throughout the experimental period, the values of inguinal subcutaneous adipose tissue increased by 10‐week‐old and were almost the same after 10‐week‐old. The liver TG levels increased from 4‐ to 8‐week‐old. However, hypertriglyceridemia, BAT whitening, and hepatic steatosis were not observed at this period. The serum TG levels increased after 10‐week‐old. Additionally, the number of whitened unilocular adipocytes with a diameter >10 μm in the BAT increased after 10‐week‐old and oil red O positive lipid droplets were usually observed in the liver at this period. Not only the serum TG levels but also the serum FFA levels increased after 18‐week‐old. Additionally, enlarged adipocytes with a diameter >130 μm and crown like structure indicating inflammatory change were often observed in the epididymal adipose tissue and retroperitoneal adipose tissue, not in mesenteric adipose tissue and inguinal subcutaneous adipose tissue, at this period. Fatty pancreas and intramuscular fat deposition were not observed throughout the experimental period.ConclusionAdipocyte hypertrophy in the visceral WAT and fatty liver could precede dyslipidemia in young OLETF rats and continuous obesity subsequently proceed to ectopic fat accumulation including BAT whitening and chronic inflammation in the epididymal adipose tissue and retroperitoneal adipose tissue with higher FFA levels. Hyperphagia mainly on carbohydrate could contribute to ectopic fat accumulation in the liver and BAT whitening, not to fatty pancreas and intramuscular fat deposition in young stage.