Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats.
OBJECTIVE
The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin-sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied.


METHODS
Adult female Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight (BW), a high-fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized to groups (n = 12) fed either low-fat or HF diets, with or without the TZD rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued, and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal (RP) adipose tissue morphology was determined from tissue collected by serial biopsies before and after 6 weeks of ROSI treatment and at sacrifice.


RESULTS
Measures of BW and adiposity did not differ among groups 6 weeks after stopping ROSI treatment. However, during treatment, ROSI in both diets significantly decreased RP adipocyte size and increased RP DNA content, and these effects continued to be observed after discontinuing treatment. ROSI administration also decreased circulating insulin, leptin, and triglycerides and increased circulating adiponectin levels; however, these effects were reversed on stopping treatment.


CONCLUSIONS
These results demonstrated that TZD-induced effects on adipocyte size and number were maintained after discontinuing treatment, even with consumption of an obesigenic diet. However, additional studies are needed to determine whether TZD-treated animals eventually achieve an adipocyte size similar to that of untreated animals at the expense of a higher BW.
Johnson
Julia A
JA
Obesity Research Center, St. Luke's-Roosevelt Hospital Center, 1111 Amsterdam Avenue, New York, NY 10025, USA.
Trasino
Steven E
SE
Ferrante
Anthony W
AW
Vasselli
Joseph R
JR
D017667:Adipocytes / Q000187:drug effects / Q000473:pathology*; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001706:Biopsy; D001835:Body Weight / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects*; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone