, Volume 50, Issue 4, pp 833-839
Date: 16 Feb 2007

Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue

Abstract

Aims/hypothesis

The association between increased (visceral) fat mass, insulin resistance and type 2 diabetes mellitus is well known. Yet, it is unclear whether the mere increase in intra-abdominal fat mass, or rather functional alterations in fat tissue in obesity contribute to the development of insulin resistance in obese patients. Here we attempted to isolate the metabolic effect of increased fat mass by fat tissue transplantation.

Methods

Epididymal fat pads were removed from male C57Bl6/J mice and transplanted intraperitoneally into male littermates (recipients), increasing the combined perigonadal fat mass by 50% (p < 0.005). At 4 and 8 weeks post-transplantation, glucose and insulin tolerance tests were performed, and insulin, NEFA and adipokines measured.

Results

Circulating levels of NEFA, adiponectin and leptin were not significantly different between transplanted and sham-operated control mice, while results of the postprandial insulin tolerance test were similar between the two groups. In contrast, under fasting conditions, the mere increase in intra-abdominal fat mass resulted in decreased plasma glucose levels (6.9 ± 0.4 vs 8.1 ± 0.3 mmol/l, p = 0.03) and a ∼20% lower AUC in the glucose tolerance test (p = 0.02) in transplanted mice. Homeostasis model assessment of insulin resistance (HOMA-IR) was 4.1 ± 0.4 in transplanted mice (vs 6.2 ± 0.7 in sham-operated controls) (p = 0.02), suggesting improved insulin sensitivity. Linear regression modelling revealed that while total body weight positively correlated, as expected, with HOMA-IR (β: 0.728, p = 0.006), higher transplanted fat mass correlated with lower HOMA-IR (β: −0.505, p = 0.031).

Conclusions/interpretation

Increasing intra-abdominal fat mass by transplantation of fat from normal mice improved, rather than impaired, fasting glucose tolerance and insulin sensitivity, achieving an effect opposite to the expected metabolic consequence of increased visceral fat in obesity.