Prolonged Decrease of Adipocyte Size after Rosiglitazone Treatment in High‐ and Low‐Fat‐Fed Rats

Abstract

JOHNSON, JULIA A., STEVEN E. TRASINO, ANTHONY W. FERRANTE, JR., AND JOSEPH R. VASSELLI. Prolonged decrease of adipocyte size after rosiglitazone treatment in high-and low-fat-fed rats. Obesity. 2007;15:2653-2663. Objective: The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulinsensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied. Research Methods and Procedures:Adult female SpragueDawley 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 ϭ 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. Discussion: 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.

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity

“…20,21 Epididymal white adipose tissue of both chow and HFD-fed NOX4-deficient mice presented larger adipocytes analyzed either as mean cell size or cell size distribution ( Figures 3a and b). Along with adipose tissue hyperthrophy, molecular signs of enhanced adipocyte differentiation and adipose tissue remodeling/hypertrophy were observed.…”

LipiD-QuanT: a novel method to quantify lipid accumulation in live cells

“…triggers new LD formation during adipogenesis ( 59 ). However, prolonged treatment is known to be antiobesogenic, to promote lipolysis, and to block LD fusion, resulting adipocytes containing small LDs ( 60,61 ).…”

“…It has been shown in animal models that rosiglitazone lowers circulating triglyceride and free fatty acids and hence improves insulin sensitivity ( 67,68 ) and reduces adipocyte size and fat accumulation in muscle ( 59,60 ). In cultured human subcutaneous adipocytes and in combination with insulin, rosiglitazone stimulated lipolysis in vitro by guest, on www.jlr.org Downloaded from .html http://www.jlr.org/content/suppl/2015/09/01/jlr.D059758.DC1 Supplemental Material can be found at:…”

Rosiglitazone balances insulin-induced exo- and endocytosis in single 3T3-L1 adipocytes

“…In addition, it was shown that pretreatment with Rosi and other TZDs leads to the reduction of the adipocyte cell size (Johnson et al, 2007;Velebit et al, 2008). This may be due to alterations in membrane dynamics; however, the mechanism of cell size reduction was not studied yet.…”