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Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats.

Julia A Johnson1, Steven E Trasino, Anthony W Ferrante

  • 1Obesity Research Center, St. Luke's-Roosevelt Hospital Center, 1111 Amsterdam Avenue, New York, NY 10025, USA.

Obesity (Silver Spring, Md.)
|December 12, 2007
PubMed
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Thiazolidinediones (TZDs) reduce adipocyte size, and these effects persist even after stopping treatment and consuming a high-fat diet. However, metabolic improvements like lower insulin and triglycerides were not maintained.

Area of Science:

  • Metabolic disease research
  • Adipose tissue biology
  • Pharmacology

Background:

  • Thiazolidinediones (TZDs) are anti-diabetic drugs known to promote adipocyte differentiation and reduce adipocyte size.
  • The long-term impact of TZD therapy on adipocyte morphology after treatment cessation, particularly under obesigenic conditions, remains understudied.

Purpose of the Study:

  • To investigate whether the reduced adipocyte size induced by thiazolidinediones (TZDs) is maintained after treatment discontinuation.
  • To assess the impact of an obesigenic diet on these TZD-induced changes in adipocyte morphology and metabolic markers.

Main Methods:

  • Adult female rats were fed either low-fat or high-fat diets and treated with rosiglitazone (ROSI) or a placebo for 6 weeks.
  • ROSI treatment was discontinued, and all rats were subsequently fed a high-fat diet for an additional 6 weeks.

Related Experiment Videos

  • Retroperitoneal adipose tissue morphology, body weight, adiposity, and circulating metabolic markers were analyzed.

    • Main Results:

    • Rosiglitazone (ROSI) treatment significantly decreased adipocyte size and increased DNA content in retroperitoneal adipose tissue, effects that persisted after treatment cessation.
    • Body weight and adiposity did not differ between groups after stopping ROSI, despite consumption of a high-fat diet.
    • While ROSI decreased insulin, leptin, and triglycerides and increased adiponectin during treatment, these metabolic improvements were reversed upon discontinuation.

    Conclusions:

    • Thiazolidinedione (TZD)-induced reductions in adipocyte size and increases in cell number are maintained after treatment cessation, even when challenged with an obesigenic diet.
    • Further research is required to determine if sustained smaller adipocyte size comes at the cost of increased body weight in TZD-treated animals.